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Hepatitis and Liver Cancer: A National Strategy for

Prevention and Control of Hepatitis B and C

Heather M. Colvin and Abigail E. Mitchell, Editors;

Committee on the Prevention and Control of Viral

Hepatitis Infections; Institute of Medicine

Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C

http://www.nap.edu/catalog/12793.html

Heather M. Colvin and Abigail E. Mitchell, Editors

Committee on the Prevention and Control of Viral Hepatitis Infections

Board on Population Health and Public Health Practice

H E PAT I T I S A N D

L I V E R C A N C E R

A National Strategy for Prevention and

Control of Hepatitis B and C

Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C

http://www.nap.edu/catalog/12793.html

THE NATIONAL ACADEMIES PRESS 500 Fifth Street, N.W. Washington, DC 20001

NOTICE: The project that is the subject of this report was approved by the Governing

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This study was supported by Contract 200-2005-13434, TO#16, between the National Acad-

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dations expressed in this publication are those of the author(s) and do not necessarily reﬂect

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Library of Congress Cataloging-in-Publication Data

Hepatitis and liver cancer : a national strategy for prevention and control of hepatitis B

and C / Heather M. Colvin and Abigail E. Mitchell, editors ; Committee on the Prevention

and Control of Viral Hepatitis Infections, Board on Population Health and Public Health

Practice.

p. ; cm.

Includes bibliographical references and index.

ISBN 978-0-309-14628-9

1. Hepatitis B—United States. 2. Hepatitis C—United States. 3. Liver—Cancer—United

States. I. Colvin, Heather M. II. Mitchell, Abigail E. III. Institute of Medicine (U.S.).

Committee on the Prevention and Control of Viral Hepatitis Infections. IV. Institute of

Medicine (U.S.). Board on Population Health and Public Health Practice. V. National

Academies Press (U.S.)

[DNLM: 1. Hepatitis B—complications—United States. 2. Hepatitis B—prevention &

control—United States. 3. Hepatitis C—complications—United States. 4. Hepatitis C—

prevention & control—United States. 5. Liver Neoplasms—prevention & control—United

States. 6. Viral Hepatitis Vaccines—therapeutic use—United States. WC 536 H5322 2010]

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Suggested citation: IOM (Institute of Medicine). 2010. Hepatitis and Liver Cancer: A National

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Academies Press.

Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C

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“Knowing is not enough; we must apply.

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Advising the Nation. Improving Health.

Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C

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Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C

http://www.nap.edu/catalog/12793.html

COMMITTEE ON THE PREVENTION AND

CONTROL OF VIRAL HEPATITIS INFECTIONS

R. Palmer Beasley (Chair), Ashbel Smith Professor and Dean Emeritus,

University of Texas, School of Public Health, Houston, Texas

Harvey J. Alter, Chief, Infectious Diseases Section, Department of

Transfusion Medicine, National Institutes of Health, Bethesda, Maryland

Margaret L. Brandeau, Professor, Department of Management Science

and Engineering, Stanford University, Stanford, California

Daniel R. Church, Epidemiologist and Adult Viral Hepatitis Coordinator,

Bureau of Infectious Disease Prevention, Response, and Services,

Massachusetts Department of Health, Jamaica Plain, Massachusetts

Alison A. Evans, Assistant Professor, Department of Epidemiology

and Biostatistics, Drexel University School of Public Health,

Drexel Institute of Biotechnology and Viral Research, Doylestown,

Pennsylvania

Holly Hagan, Senior Research Scientist, College of Nursing, New York

University, New York

Sandral Hullett, CEO and Medical Director, Cooper Green Hospital,

Birmingham, Alabama

Stacene R. Maroushek, Staff Pediatrician, Department of Pediatrics,

Hennepin County Medical Center, Minneapolis, Minnesota

Randall R. Mayer, Chief, Bureau of HIV, STD, and Hepatitis, Iowa

Department of Public Health, Des Moines, Iowa

Brian J. McMahon, Medical Director, Liver Disease and Hepatitis

Program, Alaska Native Tribal Health Consortium, Anchorage, Alaska

Martín Jose Sepúlveda, Vice President, Integrated Health Services,

International Business Machines Corporation, Somers, New York

Samuel So, Lui Hac Minh Professor, Asian Liver Center, Stanford

University School of Medicine, Stanford, California

David L. Thomas, Chief, Division of Infectious Diseases, Department of

Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland

Lester N. Wright, Deputy Commissioner and Chief Medical Ofﬁcer, New

York Department of Correctional Services, Albany, New York

Study Staff

Abigail E. Mitchell, Study Director

Heather M. Colvin, Program Ofﬁcer

Kathleen M. McGraw, Senior Program Assistant

Norman Grossblatt, Senior Editor

Rose Marie Martinez, Director, Board on Population Health and Public

Health Practice

Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C

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Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C

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vii

Reviewers

his report has been reviewed in draft form by persons chosen for

their diverse perspectives and technical expertise, in accordance with

procedures approved by the National Research Council’s (NRC’s)

Report Review Committee. The purpose of this independent review is to

provide candid and critical comments that will assist the institution in mak-

ing its published report as sound as possible and to ensure that the report

meets institutional standards for objectivity, evidence, and responsiveness

to the study charge. The review comments and draft manuscript remain

conﬁdential to protect the integrity of the deliberative process. We wish to

thank the following individuals for their review of this report:

Scott Allen, Brown University Medical School

Jeffrey Caballero, Association of Asian Paciﬁc Community Health

Organizations

Colleen Flanigan, New York State Department of Health

James Jerry Gibson, South Carolina Department of Health and

Environmental Control

Fernando A. Guerra, San Antonio Metropolitan Health District

Theodore Hammett, Abt Associates Inc.

Jay Hoofnagle, National Institute of Diabetes and Digestive and

Kidney Diseases

Charles D. Howell, University of Maryland School of Medicine

Walter A. Orenstein, Bill & Melinda Gates Foundation

Philip E. Reichert, Florida Department of Health

Charles M. Rice III, The Rockefeller University

Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C

http://www.nap.edu/catalog/12793.html

viii REVIEWERS

Tracy Swan, Treatment Action Group

Su Wang, Charles B. Wang Community Health Center

John B. Wong, Tufts Medical Center

Although the reviewers listed above have provided many constructive

comments and suggestions, they were not asked to endorse the conclusions

or recommendations, nor did they see the ﬁnal draft of the report before

its release. The review of the report was overseen by Bradford H. Gray,

Senior Fellow, The Urban Institute, and Elena O. Nightingale, Scholar-in-

Residence, Institute of Medicine. Appointed by the Institute of Medicine

and the National Research Council, they were responsible for making cer-

tain that an independent examination of the report was carried out in ac-

cordance with institutional procedures and that all review comments were

carefully considered. Responsibility for the ﬁnal content of the report rests

entirely with the author committee and the institution.

Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C

http://www.nap.edu/catalog/12793.html

Acknowledgments

he committee acknowledges the valuable contributions made by the

many persons who shared their experience and knowledge with the

committee. The committee appreciates the time and insight of the pre-

senters during the public sessions: John Ward, Dale Hu, Cindy Weinbaum,

and David Bell, Centers for Disease Control and Prevention; Chris Taylor

and Martha Saly, National Viral Hepatitis Roundtable; Lorren Sandt, Car-

ing Ambassadors Program; Joan Block, Hepatitis B Foundation; Gary

Heseltine, Council of State and Territorial Epidemiologists; William Rogers,

Centers for Medicare and Medicaid Services; Tanya Pagán Raggio Ashley,

Health Resources Services Administration; Carol Craig, National Associa-

tion of Community Health Centers; Daniel Raymond, Harm Reduction

Coalition; and Mark Kane, formerly of the Children’s Vaccine Program,

PATH. We are also grateful for the thoughtful written and verbal testimony

provided by members of the public affected by hepatitis B or hepatitis C.

Several persons contributed their expertise for this report. The com-

mittee thanks David Hutton, of the Department of Management Science

and Engineering at Stanford University; Victor Toy, Beverly David, and

Kathleen Tarleton, of IBM; Shiela Strauss, of the New York University

College of Nursing; Ellen Chang and Stephanie Chao, of the Asian Liver

Center at Stanford University; Gillian Haney, of the Massachusetts Depart-

ment of Public Health; and all the State Adult Viral Hepatitis Prevention

Coordinators that provided information to the committee.

This report would not have been possible without the diligent assistance

of Jeffrey Eﬁrd and Daniel Riedford, of the Centers for Disease Control and

Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C

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x ACKNOWLEDGMENTS

Prevention. We appreciate the assistance of Ronald Valdiserri, of the De-

partment of Veterans Affairs, for providing literature for the report.

The committee thanks the staff members of the Institute of Medicine,

the National Research Council, and the National Academies Press who

contributed to the development, production, and dissemination of this

report. The committee thanks the study director, Abigail Mitchell, and

program ofﬁcer Heather Colvin for their work in navigating this complex

topic and Kathleen McGraw for her diligent management of the committee

logistics.

This report was made possible by the support of the Division of Viral

Hepatitis and Division of Cancer Prevention and Control of the Centers

for Disease Control and Prevention, the Department of Health and Human

Services Ofﬁce of Minority Health, the Department of Veterans Affairs, and

the National Viral Hepatitis Roundtable.

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Contents

ACRONYMS AND ABBREVIATIONS xvii

SUMMARY 1

The Charge to the Committee, 2

Findings and Recommendations, 2

Surveillance, 3

Knowledge and Awareness, 8

Immunization, 9

Viral Hepatitis Services, 12

Recommendation Outcomes, 17

1 INTRODUCTION 19

Prevalence and Incidence of Hepatitis B and Hepatitis C

Worldwide, 22

Prevalence and Incidence of Hepatitis B and Hepatitis C

in the United States, 25

Hepatitis B, 25

Hepatitis C, 28

Liver Cancer and Liver Disease from Chronic Hepatitis B Virus and

Hepatitis C Virus Infections, 29

The Committee’s Task, 30

The Committee’s Approach to Its Task, 32

References, 35

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xii CONTENTS

2 SURVEILLANCE 41

Applications of Surveillance Data, 43

Outbreak Detection and Control, 44

Resource Allocation, 45

Programmatic Design and Evaluation, 45

Linking Patients to Care, 45

Disease-Speciﬁc Issues Related to Viral-Hepatitis Surveillance, 46

Identifying Acute Infections, 47

Identifying Chronic Infections, 51

Identifying Perinatal Hepatitis B, 54

Other Challenges for Hepatitis B and Hepatitis C Surveillance

Systems, 56

Infrastructure and Process-Speciﬁc Issues with Surveillance, 57

Funding Sources, 58

Program Design, 59

Reporting Systems and Requirements, 59

Capturing Data on At-Risk Populations, 61

Case Evaluation, Followup, and Partner Services, 62

Recommendations, 63

Model for Surveillance, 66

Core Surveillance, 67

Targeted Surveillance, 71

References, 72

3 KNOWLEDGE AND AWARENESS ABOUT CHRONIC

HEPATITIS B AND HEPATITIS C 79

Knowledge and Awareness Among Health-Care and Social-Service

Providers, 80

Hepatitis B, 81

Hepatitis C, 83

Recommendation, 85

Community Knowledge and Awareness, 89

Hepatitis B, 89

Hepatitis C, 93

Recommendation, 96

References, 101

4 IMMUNIZATION 109

Hepatitis B Vaccine, 109

Current Vaccination Recommendations, Requirements, and

Rates, 110

Immunization-Information Systems, 126

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CONTENTS xiii

Barriers to Hepatitis B Vaccination, 127

Hepatitis C Vaccine, 136

Feasibility of Preventing Chronic Hepatitis C, 136

Need for a Vaccine to Prevent Chronic Hepatitis C, 137

Cost Effectiveness of a Hepatitis C Vaccine, 137

References, 138

5 VIRAL HEPATITIS SERVICES 147

Current Status, 148

Components of Viral Hepatitis Services, 154

Identiﬁcation of Infected Persons, 154

Prevention, 166

Medical Management, 166

Major Gaps in Services, 170

General Population, 170

Foreign-Born People, 173

Illicit-Drug Users, 175

Pregnant Women, 181

Correctional Settings, 184

Community Health Facilities, 186

Targeting Settings That Serve At-Risk Populations, 189

References, 192

A COMMITTEE BIOGRAPHIES 209

B PUBLIC MEETING AGENDAS 215

BOXES, FIGURES, AND TABLES

Boxes

S-1 Recommendations, 4

2-1 Role of Disease Surveillance, 42

2-2 CDC Acute Hepatitis B Case Deﬁnition, 48

2-3 CDC Acute Hepatitis C Case Deﬁnition, 49

2-4 CDC Chronic Hepatitis B Case Deﬁnition, 52

2-5 CDC Hepatitis C Virus Infection Case Deﬁnition

(Past or Present), 53

2-6 CDC Perinatal Hepatitis B Virus Infection Case Deﬁnition, 55

3-1 Geographic Regions That Have Intermediate and High Hepatitis B

Virus Endemicity, 81

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xiv CONTENTS

4-1 Summary of ACIP Hepatitis B Vaccination Recommendations, 112

5-1 Summary of Recommendations Regarding Viral Hepatitis

Services, 148

5-2 Mission Statement of Centers for Disease Control and Prevention

Division of Viral Hepatitis, 150

5-3 Components of Comprehensive Viral Hepatitis Services, 155

5-4 Summary of CDC At-Risk Populations for Hepatitis B Virus

Infection, 156

5-5 Summary of CDC At-Risk Populations for Hepatitis C Virus

Infection, 158

5-6 Hepatitis B Virus-Speciﬁc Antigens and Antibodies Used for

Testing, 160

Figures

1-1 Approximate global preventable death rate from selected infectious

diseases and other causes, 2003, 20

1-2 The committee’s approach to its task, 34

2-1 Natural progression of hepatitis B infection, 46

2-2 Natural progression of hepatitis C infection, 47

4-1 Estimated cost of adult hepatitis B vaccination per quality adjusted

life year (QALY) gained for different age groups and different rates

of acute hepatitis B virus (HBV) infection incidence, 119

4-2 Trends in private health-insurance coverage, 133

5-1 Hepatitis B services model, 157

5-2 Essential viral hepatitis services for illicit-drug users, 180

Tables

1-1 Key Characteristics of Hepatitis B and Hepatitis C, 21

1-2 Burden of Selected Serious Chronic Viral Infections in the United

States, 26

4-1 Hepatitis B Vaccine Schedules for Newborns, by Maternal HBsAg

Status—ACIP Recommendations, 114

4-2 Hepatitis B Immunization Management of Preterm Infants Who

Weigh Less Than 2,000 g, by Maternal HBsAg Status—ACIP

Recommendations, 115

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CONTENTS xv

4-3 Estimated Chance That an Acute Hepatitis B Infection Becomes

Chronic with Age, 118

4-4 Studies of Hepatitis B Vaccination Rates in Injection-Drug

Users, 122

4-5 Public Health-Insurance Plans, 130

5-1 Summary of Adult Viral Hepatitis Prevention Coordinators

Survey, 153

5-2 Interpretation of Hepatitis B Serologic Diagnostic Test

Results, 161

5-3 Interpretation of Hepatitis C Virus Diagnostic Test Results, 164

5-4 Studies of Association Between Opiate Substitution Treatment and

Hepatitis C Virus Seroconversion, 178

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xvii

Acronyms and Abbreviations

AASLD American Association for the Study of Liver Diseases

ACIP Advisory Committee on Immunization Practices

ACOG American College of Obstetricians and Gynecologists

AHRQ Agency for Healthcare Research and Quality

AIDS acquired immunodeﬁciency syndrome

ALT alanine aminotransferase

anti-HBc Hepatitis B core antibody

anti-HBs Hepatitis B surface antibody

anti-HCV Hepatitis C antibody

API Asian and Paciﬁc Islander

AST aspartate transaminase

AVHPC adult viral hepatitis prevention coordinators

CDC Centers for Disease Control and Prevention

CHIP Children’s Health Insurance Program

CI conﬁdence interval

CIA enhanced chemiluminescence

CMS Centers for Medicare and Medicaid Services

DIS disease intervention specialist

DTaP diptheria and tetanus toxoids and acellular pertussis

adsorbed vaccine

DUIT drug user intervention trial

DVH Division of Viral Hepatitis

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xviii ACRONYMS AND ABBREVIATIONS

EIA enzyme immunoassay

EIP Emerging Infections Program

EPSDT early periodic screening diagnosis and treatment program

FDA Food and Drug Administration

FEHBP Federal Employee Health Beneﬁt Program

FQHC federally qualiﬁed health center

HAV Hepatitis A virus

HBIG Hepatitis B immunoglobulin

HBsAg Hepatitis B surface antigen

HBV Hepatitis B virus

HCC hepatocellular carcinoma

HCV Hepatitis C virus

HCW health-care workers

HDHP high deductable health plan

HIAA Health Insurance Association of America

HIB haemophilus inﬂuenzae type B

HIV human immunodeﬁciency virus

HMO health maintenance organization

HPV human papilloma virus

HRSA Health Resources and Services Administration

IDU injection-drug user

IIS immunization information systems

IOM Institute of Medicine

IPV inactivated polio virus

MMTP methadone maintenance treatment program

NASTAD National Alliance of State and Territorial AIDS Directors

NAT nucleic acid test

NCHHSTP National Center for HIV/AIDS, Viral Hepatitis, Sexually

Transmitted Diseases, and Tuberculosis Prevention

NEDSS National Electronic Disease Surveillance System

NETSS National Electronic Telecommunications System for

Surveillance

NGO nongovernmental organization

NHANES National Health and Nutrition Examination Survey

NIDU non-injection-drug user

NVAC National Vaccine Advisory Committee

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ACRONYMS AND ABBREVIATIONS xix

OB/GYN obstetrician/gynecologist

OMH Ofﬁce of Minority Health

OR odds ratio

PEI peer education intervention

PHIN Public Health Information Network

POS point of service

PPO preferred provider organization

PY person year

QALY quality adjusted life year

RCT randomized clinical trial

RIBA recombinant immunoblot assay

RNA ribonucleic acid

RSV respiratory syncytial virus

SAMHSA Substance Abuse and Mental Health Services

Administration

SARS severe acute respiratory syndrome

SEP syringe exchange program

STD sexually transmitted disease

STRIVE Study To Reduce Intravenous Exposures

TB tuberculosis

TCM traditional Chinese medicine

USPHS US Public Health Service

USPSTF US Preventive Services Task Force

VA Department of Veterans Affairs

vCJD variant Creutzfeldt-Jakob disease

VFC Vaccines for Children

WHO World Health Organization

Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C

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Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C

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Summary

n the next 10 years, about 150,000 people in the United States will die

from liver cancer and end-stage liver disease associated with chronic

hepatitis B and hepatitis C. It is estimated that 3.5–5.3 million people—

1–2% of the US population—are living with chronic hepatitis B virus

(HBV) or hepatitis C virus (HCV) infections. Of those, 800,000 to 1.4 mil-

lion have chronic HBV infections, and 2.7–3.9 million have chronic HCV

infections. Chronic viral hepatitis infections are 3–5 times more frequent

than HIV in the United States.

Because of the asymptomatic nature of chronic hepatitis B and hepatitis

C, most people infected with HBV and HCV are not aware that they have

been infected until they have symptoms of cirrhosis or a type of liver cancer,

hepatocellular carcinoma (HCC), many years later. About 65% and 75% of

the infected population are unaware that they are infected with HBV and

HCV, respectively. Importantly, the prevention of chronic hepatitis B and

chronic hepatitis C prevents the majority of HCC cases because HBV and

HCV are the leading causes of this type of cancer.

Although the incidence of acute HBV infection is declining in the

United States, due to the availability of hepatitis B vaccines, about 43,000

new acute HBV infections still occur each year. Of those new infections,

about 1,000 infants acquire the infection during birth from their HBV-

positive mothers. HBV is also transmitted by sexual contact with an in-

fected person, sharing injection drug equipment, and needlestick injuries.

African American adults have the highest rate of acute HBV infection in

the United States and the highest rates of acute HBV infection occur in the

southern region. People from Asia and the Paciﬁc Islands comprise the larg-

Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C

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2 HEPATITIS AND LIVER CANCER

est foreign-born population that is at risk for chronic HBV infection. The

number of people in the United States who are living with chronic HBV

infection may be increasing as a result of immigration from highly endemic

countries. On the basis of immigration patterns in the last decade, it is esti-

mated that every year 40,000–45,000 people from HBV-endemic countries

enter the United States legally.

There is no vaccine for hepatitis C. HCV is efﬁciently transmitted by

direct percutaneous exposure to infectious blood. Persons likely to have

chronic HCV infection include those who received a blood transfusion be-

fore 1992 and past or current injection-drug users (IDUs). Most IDUs in the

United States have serologic evidence of HCV infection (that is, they have

been exposed to HCV at some time). While HCV incidence appears to have

declined over the last decade, a large portion of IDUs, who often do not

have access to health-care services, are not identiﬁed by current surveillance

systems making interpretation of that trend complicated. African Ameri-

cans and Hispanics have a higher rate of HCV infection than whites.

THE CHARGE TO THE COMMITTEE

Despite federal, state, and local public health efforts to prevent and

control hepatitis B and hepatitis C, these diseases remain serious health

problems in the United States. Therefore, the Centers for Disease Control

and Prevention (CDC) in conjunction with the Department of Health and

Human Services Ofﬁce of Minority Health, the Department of Veterans

Affairs, and the National Viral Hepatitis Roundtable sought guidance from

the Institute of Medicine (IOM) in identifying missed opportunities related

to the prevention and control of HBV and HCV infections. IOM was asked

to focus on hepatitis B and hepatitis C because they are common in the

United States and can lead to chronic disease. The charge to the committee

follows.

The IOM will form a committee to determine ways to reduce new HBV

and HCV infections and the morbidity and mortality related to chronic

viral hepatitis. The committee will assess current prevention and control

activities and identify priorities for research, policy, and action. The com-

mittee will highlight issues that warrant further investigations and oppor-

tunities for collaboration between private and public sectors.

FINDINGS AND RECOMMENDATIONS

Upon reviewing evidence on the prevention and control of hepatitis B

and hepatitis C, the committee identiﬁed the underlying factors that impede

current efforts to prevent and control these diseases. Three major factors

were found:

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SUMMARY 3

1. There is a lack of knowledge and awareness about chronic viral

hepatitis on the part of health-care and social-service providers.

2. There is a lack of knowledge and awareness about chronic viral

hepatitis among at-risk populations, members of the public, and

policy-makers.

3. There is insufﬁcient understanding about the extent and seriousness

of this public-health problem, so inadequate public resources are

being allocated to prevention, control, and surveillance programs.

That situation has created several consequences:

• Inadequate disease surveillance systems underreport acute and

chronic infections, so the full extent of the problem is unknown.

• At-risk people do not know that they are at risk or how to prevent

becoming infected.

• At-risk people may not have access to preventive services.

• Chronically infected people do not know that they are infected.

• Many health-care providers do not screen people for risk factors

or do not know how to manage infected people.

• Infected people often have inadequate access to testing, social sup-

port, and medical management services.

To address those consequences, the committee offers recommendations

in four categories: surveillance, knowledge and awareness, immunization,

and services for viral hepatitis. The recommendations are discussed below,

and listed in Box S-1.

Surveillance

The viral hepatitis surveillance system in the United States is highly

fragmented and poorly developed. As a result, surveillance data do not pro-

vide accurate estimates of the current burden of disease, are insufﬁcient for

program planning and evaluation, and do not provide the information that

would allow policy-makers to allocate sufﬁcient resources to viral hepatitis

prevention and control programs. The federal government has provided

few resources—in the form of guidance, funding, and oversight—to local

and state health departments to perform surveillance for viral hepatitis.

Additional funding sources for surveillance, such as funding from states

and cities, vary among jurisdictions. The committee found little published

information on or systematic review of viral hepatitis surveillance in the

United States and offers the following recommendation to determine the

current status of the surveillance system:

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4 HEPATITIS AND LIVER CANCER

BOX S-1

Recommendations

Chapter 2: Surveillance

• 2-1. The Centers for Disease Control and Prevention should conduct

a comprehensive evaluation of the national hepatitis B and

hepatitis C public-health surveillance system.

• 2-2. The Centers for Disease Control and Prevention should develop

speciﬁc cooperative viral-hepatitis agreements with all state and

territorial health departments to support core surveillance for

acute and chronic hepatitis B and hepatitis C.

• 2-3. The Centers for Disease Control and Prevention should support

and conduct targeted active surveillance, including serologic

testing, to monitor incidence and prevalence of hepatitis B virus

and hepatitis C virus infections in populations not fully captured

by core surveillance.

Chapter 3: Knowledge and Awareness about Chronic Hepatitis B

and Hepatitis C

• 3-1. The Centers for Disease Control and Prevention should work

with key stakeholders (other federal agencies, state and local

governments, professional organizations, health-care organiza-

tions, and educational institutions) to develop hepatitis B and

hepatitis C educational programs for health-care and social-

service providers.

• 3-2. The Centers for Disease Control and Prevention should work

with key stakeholders to develop, coordinate, and evaluate inno-

vative and effective outreach and education programs to target

at-risk populations and to increase awareness in the general

population about hepatitis B and hepatitis C.

Chapter 4: Immunization

• 4-1. All infants weighing at least 2,000 grams and born to hepati-

tis B surface antigen-positive women should receive single-

antigen hepatitis B vaccine and hepatitis B immune globulin in

the delivery room as soon as they are stable and washed. The

recommendations of the Advisory Committee on Immunization

Practices should remain in effect for all other infants.

• 4-2. All states should mandate that the hepatitis B vaccine se-

ries be completed or in progress as a requirement for school

attendance.

• 4-3. Additional federal and state resources should be devoted to

increasing hepatitis B vaccination of at-risk adults.

• 4-4. States should be encouraged to expand immunization-information

systems to include adolescents and adults.

• 4-5. Private and public insurance coverage for hepatitis B vaccina-

tion should be expanded.

• 4-6. The federal government should work to ensure an adequate,

accessible, and sustainable hepatitis B vaccine supply.

• 4-7. Studies to develop a vaccine to prevent chronic hepatitis C virus

infection should continue.

Chapter 5: Viral Hepatitis Services

• 5-1. Federally funded health-insurance programs—such as Medi-

care, Medicaid, and the Federal Employees Health Beneﬁts

Program—should incorporate guidelines for risk-factor screen-

ing for hepatitis B and hepatitis C as a required core compo-

nent of preventive care so that at-risk people receive serologic

testing for hepatitis B virus and hepatitis C virus and chronically

infected patients receive appropriate medical management.

• 5-2. The Centers for Disease Control and Prevention, in conjunction

with other federal agencies and state agencies, should provide

resources for the expansion of community-based programs that

provide hepatitis B screening, testing, and vaccination services

that target foreign-born populations.

• 5-3. Federal, state, and local agencies should expand programs to

reduce the risk of hepatitis C virus infection through injection-

drug use by providing comprehensive hepatitis C virus preven-

tion programs. At a minimum, the programs should include

access to sterile needle syringes and drug-preparation equip-

ment because the shared use of these materials has been

shown to lead to transmission of hepatitis C virus.

• 5-4. Federal and state governments should expand services to

reduce the harm caused by chronic hepatitis B and hepati-

tis C. The services should include testing to detect infection,

counseling to reduce alcohol use and secondary transmission,

hepatitis B vaccination, and referral for or provision of medical

management.

• 5-5. Innovative, effective, multicomponent hepatitis C virus preven-

tion strategies for injection-drug users and non-injection-drug

users should be developed and evaluated to achieve greater

control of hepatitis C virus transmission.

• 5-6. The Centers for Disease Control and Prevention should pro-

vide additional resources and guidance to perinatal hepatitis B

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SUMMARY 5

BOX S-1

Recommendations

Chapter 2: Surveillance

• 2-1. The Centers for Disease Control and Prevention should conduct

a comprehensive evaluation of the national hepatitis B and

hepatitis C public-health surveillance system.

• 2-2. The Centers for Disease Control and Prevention should develop

speciﬁc cooperative viral-hepatitis agreements with all state and

territorial health departments to support core surveillance for

acute and chronic hepatitis B and hepatitis C.

• 2-3. The Centers for Disease Control and Prevention should support

and conduct targeted active surveillance, including serologic

testing, to monitor incidence and prevalence of hepatitis B virus

and hepatitis C virus infections in populations not fully captured

by core surveillance.

Chapter 3: Knowledge and Awareness about Chronic Hepatitis B

and Hepatitis C

• 3-1. The Centers for Disease Control and Prevention should work

with key stakeholders (other federal agencies, state and local

governments, professional organizations, health-care organiza-

tions, and educational institutions) to develop hepatitis B and

hepatitis C educational programs for health-care and social-

service providers.

• 3-2. The Centers for Disease Control and Prevention should work

with key stakeholders to develop, coordinate, and evaluate inno-

vative and effective outreach and education programs to target

at-risk populations and to increase awareness in the general

population about hepatitis B and hepatitis C.

Chapter 4: Immunization

• 4-1. All infants weighing at least 2,000 grams and born to hepati-

tis B surface antigen-positive women should receive single-

antigen hepatitis B vaccine and hepatitis B immune globulin in

the delivery room as soon as they are stable and washed. The

recommendations of the Advisory Committee on Immunization

Practices should remain in effect for all other infants.

• 4-2. All states should mandate that the hepatitis B vaccine se-

ries be completed or in progress as a requirement for school

attendance.

• 4-3. Additional federal and state resources should be devoted to

increasing hepatitis B vaccination of at-risk adults.

• 4-4. States should be encouraged to expand immunization-information

systems to include adolescents and adults.

• 4-5. Private and public insurance coverage for hepatitis B vaccina-

tion should be expanded.

• 4-6. The federal government should work to ensure an adequate,

accessible, and sustainable hepatitis B vaccine supply.

• 4-7. Studies to develop a vaccine to prevent chronic hepatitis C virus

infection should continue.

Chapter 5: Viral Hepatitis Services

• 5-1. Federally funded health-insurance programs—such as Medi-

care, Medicaid, and the Federal Employees Health Beneﬁts

Program—should incorporate guidelines for risk-factor screen-

ing for hepatitis B and hepatitis C as a required core compo-

nent of preventive care so that at-risk people receive serologic

testing for hepatitis B virus and hepatitis C virus and chronically

infected patients receive appropriate medical management.

• 5-2. The Centers for Disease Control and Prevention, in conjunction

with other federal agencies and state agencies, should provide

resources for the expansion of community-based programs that

provide hepatitis B screening, testing, and vaccination services

that target foreign-born populations.

• 5-3. Federal, state, and local agencies should expand programs to

reduce the risk of hepatitis C virus infection through injection-

drug use by providing comprehensive hepatitis C virus preven-

tion programs. At a minimum, the programs should include

access to sterile needle syringes and drug-preparation equip-

ment because the shared use of these materials has been

shown to lead to transmission of hepatitis C virus.

• 5-4. Federal and state governments should expand services to

reduce the harm caused by chronic hepatitis B and hepati-

tis C. The services should include testing to detect infection,

counseling to reduce alcohol use and secondary transmission,

hepatitis B vaccination, and referral for or provision of medical

management.

• 5-5. Innovative, effective, multicomponent hepatitis C virus preven-

tion strategies for injection-drug users and non-injection-drug

users should be developed and evaluated to achieve greater

control of hepatitis C virus transmission.

• 5-6. The Centers for Disease Control and Prevention should pro-

vide additional resources and guidance to perinatal hepatitis B

continued

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6 HEPATITIS AND LIVER CANCER

Recommendation 2-1. The Centers for Disease Control and Prevention

should conduct a comprehensive evaluation of the national hepatitis B

and hepatitis C public-health surveillance system.

The evaluation should, at a minimum,

• Include assessment of the system’s attributes, including complete-

ness, data quality and accuracy, timeliness, sensitivity, speciﬁcity,

predictive value positive, representativeness, and stability.

• Be consistent with CDC’s Updated Guidelines for Evaluating Public

Health Surveillance Systems.

• Be used to guide the development of detailed technical guidance

and standards for viral hepatitis surveillance.

• Be published in a report.

prevention program coordinators to expand and enhance the

capacity to identify chronically infected pregnant women and

provide case-management services, including referral for ap-

propriate medical management.

• 5-7. The National Institutes of Health should support a study of

he effectiveness and safety of peripartum antiviral therapy to

reduce and possibly eliminate perinatal hepatitis B virus trans-

mission from women at high risk for perinatal transmission.

• 5-8. The Centers for Disease Control and Prevention and the De-

partment of Justice should create an initiative to foster partner-

ships between health departments and corrections systems to

ensure the availability of comprehensive viral hepatitis services

for incarcerated people.

• 5-9. The Health Resources and Services Administration should

provide adequate resources to federally funded community

health facilities for provision of comprehensive viral-hepatitis

services.

• 5-10. The Health Resources and Services Administration and the

Centers for Disease Control and Prevention should provide re-

sources and guidance to integrate comprehensive viral hepatitis

services into settings that serve high-risk populations such as

STD clinics, sites for HIV services and care, homeless shelters,

and mobile health units.

BOX S-1 Continued

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SUMMARY 7

The committee offers the following recommendations aimed at mak-

ing viral hepatitis surveillance systems more consistent among jurisdictions

and improving their ability to collect and report data on acute and chronic

hepatitis B and hepatitis C more accurately:

Recommendation 2-2. The Centers for Disease Control and Prevention

should develop speciﬁc cooperative viral-hepatitis agreements with all

state and territorial health departments to support core surveillance for

acute and chronic hepatitis B and hepatitis C.

The agreements should include

• A funding mechanism and guidance for core surveillance

activities.

• Implementation of performance standards regarding revised and

standardized case deﬁnitions, speciﬁcally through the use of

 o Revised case-reporting forms with required, standardized

components.

 o Case evaluation and followup.

• Support for developing and implementing automated data-collection

systems, including

 o Electronic laboratory reporting.

 o Electronic medical-record extraction systems.

 o Web-based, Public Health Information Network-compliant re-

porting systems.

Recommendation 2-3. The Centers for Disease Control and Preven-

tion should support and conduct targeted active surveillance, including

serologic testing, to monitor incidence and prevalence

of hepatitis B

virus and hepatitis C virus infections in populations not fully captured

by core surveillance.

• Active surveillance should be conducted in speciﬁc (sentinel) geo-

graphic regions and populations.

• Appropriate serology, molecular biology, and followup will allow for

distinction between acute and chronic hepatitis B and hepatitis C.

Incidence refers to the number of new cases within a speciﬁed period of time. Prevalence

refers to the number of existing cases in a speciﬁed population at a designated time.

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8 HEPATITIS AND LIVER CANCER

Knowledge and Awareness

The committee found that there is relatively poor awareness about

hepatitis B and hepatitis C among health-care providers, social-service

providers (such as staff of drug-treatment facilities and immigrant-services

centers), and the public, especially important, among members of speciﬁc

at-risk populations. Lack of awareness about the prevalence of chronic viral

hepatitis in the United States and the target populations and appropriate

methodology for screening, testing, and medical management of chronic

hepatitis B and hepatitis C probably contributes to continuing transmission;

missing of opportunities for prevention, including vaccination; missing of

opportunities for early diagnosis and medical care; and poor health out-

comes in infected people.

To improve knowledge and awareness among health-care pro-

viders and social-service providers, the committee offers the following

recommendation:

Recommendation 3-1. The Centers for Disease Control and Prevention

should work with key stakeholders (other federal agencies, state and

local governments, professional organizations, health-care organiza-

tions, and educational institutions) to develop hepatitis B and hepatitis

C educational programs for health-care and social-service providers.

The educational programs should include at least the following

components:

• Information about the prevalence and incidence of acute and chronic

hepatitis B and hepatitis C both in the general US population and

in at-risk populations, particularly foreign-born populations in the

case of hepatitis B, and IDUs and incarcerated populations in the

case of hepatitis C.

• Guidance on screening for risk factors associated with hepatitis B

and hepatitis C.

• Information about hepatitis B and hepatitis C prevention, hepatitis

B immunization, and medical monitoring of chronically infected

patients.

• Information about prevention of HBV and HCV transmission in

hospital and nonhospital health-care settings.

• Information about discrimination and stigma associated with hepa-

titis B and hepatitis C and guidance on reducing them.

• Information about health disparities related to hepatitis B and

hepatitis C.

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SUMMARY 9

To increase knowledge and awareness about hepatitis B and hepatitis

C in at-risk populations and the general population, the committee offers

the following recommendation:

Recommendation 3-2. The Centers for Disease Control and Prevention

should work with key stakeholders to develop, coordinate, and evalu-

ate innovative and effective outreach and education programs to target

at-risk populations and to increase awareness in the general population

about hepatitis B and hepatitis C.

The programs should be linguistically and culturally appropriate and

should advance integration of viral hepatitis and liver-health education into

other health programs that serve at-risk populations. They should incorpo-

rate interventions that meet the following goals:

• Promote better understanding of HBV and HCV infections, trans-

mission, prevention, and treatment in the at-risk and general

populations.

• Promote increased hepatitis B vaccination rates among children

and at-risk adults.

• Educate pregnant women and women of childbearing age about

hepatitis B prevention.

• Reduce perinatal HBV infections and improve at-birth immuniza-

tion rates.

• Increase testing rates in at-risk populations.

• Reduce stigmatization of chronically infected people.

• Promote safe injections among IDUs and safe drug use among non-

injection-drug users (NIDUs).

• Provide culturally and linguistically appropriate educational infor-

mation for all persons who have tested positive for chronic HBV

or HCV infections and those who are receiving treatment.

• Encourage notiﬁcation of close household and sexual contacts of

infected people to be tested for HBV and HCV and encourage

hepatitis B vaccination of close contacts.

Immunization

The longstanding availability of effective hepatitis B vaccines makes

the elimination of new HBV infections possible, particularly in children.

As noted above, about 1,000 newborns are infected by their HBV-positive

mothers at birth each year in the United States, and that number has not

declined in the last decade. To prevent transmission of HBV from moth-

ers to their newborns, the Advisory Committee on Immunization Practices

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10 HEPATITIS AND LIVER CANCER

(ACIP) recommends that infants born to mothers who are positive for

hepatitis B surface antigen (HBsAg) receive hepatitis B immune globulin

and a ﬁrst dose of the hepatitis B vaccine within 12 hours of birth. To

improve adherence to that guideline, the committee offers the following

recommendation:

Recommendation 4-1. All infants weighing at least 2,000 grams and

born to hepatitis B surface antigen-positive women should receive

single-antigen hepatitis B vaccine and hepatitis B immune globulin in

the delivery room as soon as they are stable and washed. The recom-

mendations of the Advisory Committee on Immunization Practices

should remain in effect for all other infants.

The ACIP recommends administration of the hepatitis B vaccine series

to unvaccinated children and young adults under 19 years old. School-entry

mandates have been shown to increase hepatitis B vaccination rates and to

reduce disparities in vaccination rates. Overall, hepatitis B vaccination rates

in school-age children are high (for example, about 80% of states reported

at least 95% hepatitis B vaccine coverage of children in kindergarten in

2006–2007), but there is variability in coverage among states. Additionally,

there are racial and ethnic disparities in childhood vaccination rates—Asian

and Paciﬁc Islander (API), Hispanic, and African American children have

lower vaccination rates than non-Hispanic white children. Regarding vac-

cination of children and adults under 19 years old, the committee offers the

following recommendation:

Recommendation 4-2. All states should mandate that the hepatitis B

vaccine series be completed or in progress as a requirement for school

attendance.

Hepatitis B vaccination for adults is directed at high-risk groups—

people at risk for HBV infection from infected household contact and sex

partners, from injection-drug use, from occupational exposure to infected

blood or body ﬂuids, and from travel to regions that have high or interme-

diate HBV endemicity. Only about half the adults who are at high risk for

HBV infection receive the hepatitis B vaccine. Low coverage of high-risk

adults is attributed to the lack of dedicated vaccine programs; limitations

of funding, insurance coverage, and cost-sharing; and noncompliance of

the involved populations. To increase the rate of hepatitis B vaccination of

at-risk adults, the committee offers the following recommendation:

Recommendation 4-3. Additional federal and state resources should be

devoted to increasing hepatitis B vaccination of at-risk adults.

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SUMMARY 11

• Correctional institutions should offer hepatitis B vaccination to all

incarcerated persons. Accelerated schedules for vaccine administra-

tion should be considered for jail inmates.

• Organizations that serve high-risk populations should offer the

hepatitis B vaccination series.

• Efforts should be made to improve identiﬁcation of at-risk

adults. Health-care providers should routinely seek risk behav-

ior histories from adult patients through direct questioning and

self-assessment.

• Efforts should be made to increase rates of completion of the vac-

cine series in adults.

• Federal and state agencies should annually determine gaps in hepa-

titis B vaccine coverage among at-risk adults and estimate the

resources needed to ﬁll those gaps.

Immunization-information systems are used for collection and con-

solidation of vaccination data from multiple health-care providers, vaccine

management, adverse-event reporting, and tracking lifespan vaccination

histories. States have made progress on developing and implementing im-

munization-information systems, particularly with regard to collecting vac-

cination data on children. The committee believes that it is also important

to include vaccination data on adolescents and adults in immunization

information systems and offers the following recommendation:

Recommendation 4-4. States should be encouraged to expand

immunization-information systems to include adolescents and adults.

Coverage for hepatitis B vaccination is greater for children and youths

than for adults. Except for Medicaid’s Early Periodic Screening, Diag-

nosis, and Treatment entitlement, public-health insurance often contains

cost-sharing, which may create a barrier to vaccination for some people.

Private health insurance has gaps for vaccination coverage because it does

not universally cover all ACIP-recommended vaccinations for children and

adults. Furthermore, most privately insured persons are required to pay to

receive vaccinations. To reduce barriers to children and adults for hepatitis

B vaccination, the committee offers the following recommendation:

Recommendation 4-5. Private and public insurance coverage for hepa-

titis B vaccination should be expanded.

• Public Health Section 317 should be expanded with sufﬁcient fund-

ing to become the public safety net for underinsured and uninsured

adults to receive the hepatitis B vaccination.

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12 HEPATITIS AND LIVER CANCER

• All private insurance plans should include coverage for all ACIP-

recommended vaccinations. Hepatitis B vaccination should be free

of any deductible so that ﬁrst-dollar coverage exists for this preven-

tive service.

There has not been a national shortage of the hepatitis B vaccine, how-

ever, temporary supply problems occurred with this vaccine in 2008 (adult

and dialysis formulations of Recombivax HB) and 2009 (pediatric formula-

tions of Recombivax HB and Pediatric Engerix-B). A shortage was avoided

because other manufacturers were able to provide an adequate supply of the

vaccine in adult and dialysis formulations, and CDC released doses of pe-

diatric vaccine from its stockpile. To prevent future supply problems of the

hepatitis B vaccine, the committee offers the following recommendation:

Recommendation 4-6. The federal government should work to ensure

an adequate, accessible, and sustainable hepatitis B vaccine supply.

Efforts are going on to develop a vaccine for hepatitis C, which could

substantially enhance hepatitis C prevention efforts. The committee recog-

nizes the need for a safe, effective, and affordable hepatitis C vaccine and

offers the following recommendation:

Recommendation 4-7. Studies to develop a vaccine to prevent chronic

hepatitis C virus infection should continue.

Viral Hepatitis Services

Health services related to viral hepatitis prevention, risk-factor screen-

ing and serologic testing,

and medical management are both sparse and

fragmented among entities at the federal, state, and local levels. The com-

mittee believes that a coordinated approach is necessary to reduce the

numbers of new HBV and HCV infections, illnesses, and deaths associated

with these infections. Comprehensive viral hepatitis services should have

ﬁve core components: outreach and awareness, prevention of new infec-

tions, identiﬁcation of infected people, social and peer support, and medical

management of infected people.

The committee identiﬁed major gaps in viral hepatitis services for

the general population and speciﬁc groups that are heavily affected by

HBV and HCV infections: foreign-born populations, illicit-drug users, and

Risk-factor screening is the process of determining whether a person is at risk for being

chronically infected or becoming infected with HBV or HCV. Serologic testing is laboratory

testing of blood specimens for biomarker conﬁrmation of HBV or HCV infection.

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SUMMARY 13

pregnant women. It also examined venues that provide services to at-risk

groups: correctional facilities, community health facilities, STD and HIV

clinics, shelter-based programs, and mobile health units. The committee

offers recommendations to address major deﬁciencies for each group and

health-care venue.

General Population

Most people who are chronically infected with HBV or HCV are un-

aware of their infection status. As treatments for chronic hepatitis B and C

improve, it becomes critical to identify chronically infected people. There-

fore, it is important that the general population have access to screening

and testing services so that people who are at risk for viral hepatitis can

be identiﬁed. The federal government is the largest purchaser of health

insurance nationally and is well positioned to be the leader in the develop-

ment and enforcement of guidelines to ensure that the people for whom it

provides health care have access to risk-factor screening, serologic testing

for HBV and HCV, and appropriate medical management.

Recommendation 5-1. Federally funded health-insurance programs—

such as Medicare, Medicaid, and the Federal Employees Health Ben-

eﬁts Program—should incorporate guidelines for risk-factor screening

for hepatitis B and hepatitis C as a required core component of pre-

ventive care so that at-risk people receive serologic testing for hepatitis

B virus and hepatitis C virus and chronically infected patients receive

appropriate medical management.

Foreign-Born Populations

Nearly half of US foreign-born people, or 6% of the total US popula-

tion, originate in HBV-endemic countries. Thus, there is a growing urgency

for culturally appropriate programs to provide hepatitis B screening and

related services to this high-risk population. There is a pervasive lack of

knowledge about hepatitis B among Asians and Paciﬁc Islanders, and this

is probably also the case for other foreign-born people in the United States.

The lack of awareness in foreign-born populations from HBV-endemic

countries is compounded by the gaps in knowledge and preventive practice

among health-care and social-service providers, particularly those who

serve a large number of foreign-born, high-risk patients. The committee be-

lieves that the needs of foreign-born people are best met with the approach

outlined in Recommendations 3-1 and 3-2. The community-based approach

as outlined in Recommendation 3-2 would be strengthened by additional

resources to provide screening, testing, and vaccination services.

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14 HEPATITIS AND LIVER CANCER

Recommendation 5-2. The Centers for Disease Control and Prevention,

in conjunction with other federal agencies and state agencies, should

provide resources for the expansion of community-based programs

that provide hepatitis B screening, testing, and vaccination services that

target foreign-born populations.

Illicit-Drug Users

HBV and HCV infection rates in illicit-drug users are high, particularly

in IDUs. HCV is easily transmitted among IDUs, and methods to promote

safe injection can be considered essential for HCV control. However, safe-

injection strategies alone are insufﬁcient to control HCV transmission.

Prevention of HCV infection is a function of multiple factors—safe-injec-

tion strategies, education, testing, and drug treatment—so an integrated

approach that includes all these elements is more likely to be effective in

preventing hepatitis C.

Recommendation 5-3. Federal, state, and local agencies should expand

programs to reduce the risk of hepatitis C virus infection through

injection-drug use by providing comprehensive hepatitis C virus pre-

vention programs. At a minimum, the programs should include access

to sterile needle syringes and drug-preparation equipment because the

shared use of these materials has been shown to lead to transmission

of hepatitis C virus.

Although illicit-drug use is associated with many serious acute and

chronic medical conditions, health-care use among drug users is lower than

among persons who do not use illicit drugs. Health care for both IDUs and

NIDUs is sporadic and typically received in hospital emergency rooms,

corrections facilities, and STD clinics. Given that population’s poor access

to health care and services, it is important to have prevention and care ser-

vices in settings that IDUs and NIDUs are likely to frequent or to develop

programs that will draw them into care.

Recommendation 5-4. Federal and state governments should expand

services to reduce the harm caused by chronic hepatitis B and hepatitis

C. The services should include testing to detect infection, counseling to

reduce alcohol use and secondary transmission, hepatitis B vaccination,

and referral for or provision of medical management.

Studies have shown that the ﬁrst few years after onset of injection-

drug use constitute a high-risk period in which the rate of HCV infection

can exceed 40%. Preventing the transition from non-injection-drug use

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SUMMARY 15

to injection-drug use will probably avert many HCV infections. The com-

mittee therefore offers the following research recommendation:

Recommendation 5-5. Innovative, effective, multicomponent hepatitis

C virus prevention strategies for injection-drug users and non-injection-

drug users should be developed and evaluated to achieve greater con-

trol of hepatitis C virus transmission. In particular,

• Hepatitis C prevention programs for persons who smoke or sniff

heroin, cocaine, and other drugs should be developed and tested.

• Programs to prevent the transition from noninjection use of illicit

drugs to injection should be developed and implemented.

Pregnant Women

States and large metropolitan areas are eligible to receive federal fund-

ing to support perinatal hepatitis B prevention programs through CDC’s

National Center for Immunization and Respiratory Diseases. Comprehen-

sive programs have been shown to be effective not only in identifying HBV-

infected pregnant women but in providing other case-management services

(for example, testing of household and sexual contacts and referral to

medical care). However, most programs are understaffed and underfunded

and cannot offer adequate case-management services.

Recommendation 5-6. The Centers for Disease Control and Prevention

should provide additional resources and guidance to perinatal hepa-

titis B prevention program coordinators to expand and enhance the

capacity to identify chronically infected pregnant women and provide

case-management services, including referral for appropriate medical

management.

Although an increasing number of effective HBV antiviral suppressive

medications have become available for the management of chronic HBV

infection, very little research has been done on the use of these medications

during the last trimester of pregnancy to eliminate the risk of perinatal

transmission. The committee believes that there is a need to fund research

to guide the effective use of antiviral medications late in pregnancy to

prevent maternofetal HBV transmission, and offers the following research

recommendation:

Recommendation 5-7. The National Institutes of Health should sup-

port a study of the effectiveness and safety of peripartum antiviral

therapy to reduce and possibly eliminate perinatal hepatitis B virus

transmission from women at high risk for perinatal transmission.

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16 HEPATITIS AND LIVER CANCER

Correctional Facilities

Incarcerated populations have higher rates of HBV and HCV infec-

tions than the general population. Screening of all incarcerated people for

risk factors can identify those who need blood tests for infection and, if

appropriate, treatment.

Recommendation 5-8. The Centers for Disease Control and Preven-

tion and the Department of Justice should create an initiative to foster

partnerships between health departments and corrections systems to

ensure the availability of comprehensive viral hepatitis services for

incarcerated people.

Community Health Centers

The Health Resources and Services Administration administers grant

programs across the country to deliver primary care to uninsured and

underinsured people in community health centers, migrant health centers,

homeless programs, and public-housing primary-care programs. In general,

funding of viral hepatitis services at community health centers is inad-

equate. Because community health centers provide primary health care for

many people who are at risk for hepatitis B and hepatitis C, it is important

for them to offer comprehensive viral hepatitis services.

Recommendation 5-9. The Health Resources and Services Adminis-

tration should provide adequate resources to federally funded com-

munity health facilities for provision of comprehensive viral-hepatitis

services.

Other Settings That Target At-Risk Populations

STD and HIV clinics, shelter-based programs, and mobile health units

are settings that serve populations that are at risk for hepatitis B and hepa-

titis C. The populations that use the settings may not have access to care

through traditional health-care venues. Integration of viral hepatitis services

into those settings creates opportunities to identify at-risk clients and to get

them other services that they need.

Recommendation 5-10. The Health Resources and Services Admin-

istration and the Centers for Disease Control and Prevention should

provide resources and guidance to integrate comprehensive viral hepa-

titis services into settings that serve high-risk populations such as STD

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SUMMARY 17

clinics, sites for HIV services and care, homeless shelters, and mobile

health units.

RECOMMENDATION OUTCOMES

The committee believes that implementation of its recommendations

would lead to reductions in new HBV and HCV infections, in medical

complications and deaths that result from these viral infections of the liver,

and in total health costs. Advances in three major categories will be needed:

in knowledge and awareness about chronic viral hepatitis among health-

care and social-service providers, the general public, and policy-makers; in

improvement and better integration of viral hepatitis services, including ex-

panded hepatitis B vaccination coverage; and in improvement of estimates

of the burden of disease for resource-allocation purposes.

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Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C

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Introduction

he global epidemic of hepatitis B and hepatitis C is a serious

public-health problem. Using mortality data from 2003, Weiss and

McMichael (2004) ranked the public-health importance of various

infectious diseases and other conditions (see Figure 1-1). Those data under-

score that chronic hepatitis B and hepatitis C are among the leading causes

of preventable death worldwide.

Hepatitis B and hepatitis C are contagious liver diseases caused by the

hepatitis B virus (HBV) and the hepatitis C virus (HCV), respectively. HBV

is a 42-nanometer, partially double-stranded DNA virus classiﬁed in the

Hepadnaviridae family; there are eight major HBV genotypes. HCV is a

55-nanometer, enveloped, positive-strand RNA virus classiﬁed as a separate

genus, Hepacavirus, in the Flaviviridae family; there are at least six major

HCV genotypes.

Hepatitis B and hepatitis C can be either acute or chronic. The acute

form is a short-term illness that occurs within the ﬁrst 6 months after a per-

son is exposed to HBV or HCV. The diseases can become chronic, although

this does not always happen and, particularly in the case of hepatitis B, the

likelihood of chronicity depends on a person’s age at the time of infection.

Chronic hepatitis B and chronic hepatitis C are serious and can result in

liver cirrhosis and a type of liver cancer, hepatocellular carcinoma (HCC).

The prevention of chronic hepatitis B and chronic hepatitis C prevents the

majority of HCC cases because HBV and HCV are the leading causes of

this type of cancer. Key characteristics of hepatitis B and hepatitis C are

summarized in Table 1-1 and discussed below and in later chapters.

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20 HEPATITIS AND LIVER CANCER

Tobacco

Other causes

Malaria

Non-HIV TB

Road accidents

vCJD

Hospital infection

Suicide

Log

global death rate

HIV

Caused by viruses

Dengue

HPV

Ebola

Hanta

West Nile

Flu

Polio

SARS

Measles

HBV + HCV

RSV, Rota

Figure 1-1 Hepatitis

R01623

vector editable

FIGURE 1-1 Approximate global preventable death rate from selected infectious

diseases and other causes, 2003.

Abbreviations: HIV, human immunodeﬁciency virus; HBV, hepatitis B virus; HCV,

hepatitis C virus; RSV, respiratory syncytial virus; HPV, human papilloma vi-

rus; SARS, severe acute respiratory syndrome; TB, tuberculosis; vCJD, variant

Creutzfeldt-Jakob disease.

SOURCE: Weiss and McMichael, 2004. Reprinted with permission from Macmillan

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INTRODUCTION 21

TABLE 1-1 Key Characteristics of Hepatitis B and Hepatitis C

Hepatitis B Hepatitis C

Causative agent Partially double-stranded DNA

virus

Hepadnaviridae family

Enveloped, positive-strand RNA

virus

Hepacavirus genus, Flaviviridae

family

Statistics In the United States, 0.8–1.4

million people are chronically

infected with HBV

In the United States, 2.7–3.9

million people are chronically

infected with HCV

Routes of

transmission

Contact with infectious blood,

semen, and other body ﬂuids,

primarily through:

• Birth to an infected mother

• Sexual contact with an

infected person

• Sharing of contaminated

needles, syringes, or other

injection-drug equipment

Less commonly through:

• Contact with infectious

blood through medical

procedures

Contact with blood of an infected

person, primarily through:

• Sharing of contaminated

needles, syringes, or other

injection-drug equipment

Less commonly through:

• Sexual contact with an infected

person

• Birth to an infected mother

• Contact with infectious blood

through medical procedures

Persons at risk • Persons born in geographic

regions that have HBsAg

prevalence of at least 2%

• Infants born to infected

mothers

• Household contacts of

persons who have chronic

HBV infection

• Sex partners of infected

persons

• Injection-drug users

• Sexually active persons

who are not in long-term,

mutually monogamous

relationships (for example,

more than one sex partner

during previous 6 months)

• Men who have sex with men

• Persons who have ever injected

illegal drugs, including those

who injected only once many

years ago

• Recipients of clotting-factor

concentrates made before 1987

• Recipients of blood transfusions

or solid-organ transplants

before July 1992

• Patients who have ever received

long-term hemodialysis

treatment

• Persons who have known

exposures to HCV, such as

health-care workers after

needlesticks involving HCV-

positive blood and recipients of

blood or organs from donors

who later tested HCV-positive

• All persons who have HIV

infection

continued

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22 HEPATITIS AND LIVER CANCER

Hepatitis B Hepatitis C

Persons at risk • Health-care and public-

safety workers at risk for

occupational exposure to

blood or blood-contaminated

body ﬂuids

• Residents and staff of

facilities for developmentally

disabled persons

• Persons who have chronic

liver disease

• Hemodialysis patients

• Travelers to countries that

have intermediate or high

prevalence of HBV infection

• Patients who have signs or

symptoms of liver disease (for

example, abnormal liver-enzyme

tests)

• Children born to HCV-positive

mothers (to avoid detecting

maternal antibody, these

children should not be tested

before the age of 18 months)

Potential for

chronic infection

Among newly infected,

unimmunized persons, chronic

infection occurs in:

• >90% of infants

• 25–50% of children aged

1–5 years

• 6–10% of older children and

adults

75–85% of newly infected persons

develop chronic infection

Clinical outcomes • 15–25% of chronically

infected persons will die from

cirrhosis, liver failure, or

hepatocellular carcinoma

• 3,000 deaths each year are

due to hepatitis B-related

liver disease in the United

States

• 60–70% of chronically infected

persons develop chronic liver

disease

• 5–20% develop cirrhosis over a

period of 20–30 years

• 1–5% will die from cirrhosis or

hepatocellular carcinoma

• 12,000 deaths each year are

due to hepatitis C-related liver

disease in the United States

Abbreviations: HBV, hepatitis B virus; HCV, hepatitis C virus; HBsAg, hepatitis B surface

antigen.

SOURCE: Adapted from CDC, 2009a.

TABLE 1-1 Continued

PREVALENCE AND INCIDENCE OF

HEPATITIS B AND HEPATITIS C WORLDWIDE

Worldwide, about 1 in 12 persons (480–520 million people) are chroni-

cally infected with HBV or HCV (Lavanchy, 2008; WHO, 2009). An

estimated 78% of cases of primary liver cancer (HCC) and 57% of cases

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INTRODUCTION 23

of liver cirrhosis are caused by chronic HBV or HCV infection (Perz et

al., 2006). Chronic liver disease due to coinfection with HBV or HCV has

become a major cause of death in persons infected with HIV (Sulkowski,

2008), and coinfection presents additional treatment challenges (Kumar

et al., 2008). It is estimated that HBV and HCV infections cause nearly a

million deaths each year (Perz et al., 2006).

Chronic viral hepatitis is a silent killer. Without testing for infection,

many chronically infected persons are not aware that they have been in-

fected until symptoms of advanced liver disease appear. Advanced liver

cancer has a 5-year survival rate of below 5% (American Cancer Society,

2009). Although much progress has been made in reducing the morbidity

and mortality through effective treatment of chronic viral hepatitis, there

is no global program to provide chronically infected persons with access to

affordable treatment.

HBV is 50–100 times more infectious than HIV (WHO, 2009). Acute

HBV infection in adults, although often asymptomatic, can cause severe ill-

ness and is associated with a 0.5–1% risk of death from liver failure (CDC,

2007). Chronic HBV infection, which occurs when the acute infection is not

cleared by the immune system, is associated with a 15–25% risk of prema-

ture death from liver cancer or end-stage liver disease (Beasley and Hwang,

1991; WHO, 2009). The World Health Organization (WHO) estimates that

up to 2 billion people worldwide have been infected with HBV; about 350

million people live with chronic HBV infection, and about 600,000 people

die from HBV-related liver disease or HCC each year (WHO, 2009).

The major transmission routes and prevalence of chronic HBV infec-

tion vary by age and geography. Primary HBV infection acquired at an

early age (through vertical transmission from an infected mother to her

newborn or horizontal transmission during early childhood) is associ-

ated with the highest risk of chronic infection and is common in people

born in or residing in the highly endemic countries of the western Paciﬁc

region, Asia, and sub-Saharan Africa (Shepard et al., 2006). In countries

with a low prevalence of HBV carriers, primary infection usually occurs

during adolescence or young adulthood as a result of unsafe injections and

unprotected sexual activity. An estimated 21 million new HBV infections

each year are due to unsafe injections in health-care settings (Hauri et al.,

2004). Hepatitis B is also a major basis for social injustice in some endemic

countries. For example, myths and misinformation about modes of HBV

transmission have resulted in widespread discrimination against chronically

infected persons in some endemic countries, such as China, the country

with the world’s largest population of chronically infected people, who are

not allowed to work in the food industry, are often required to undergo

routine pre-employment HBV testing, and can be expelled from school or

work because of a positive test (The Economist, 2006).

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24 HEPATITIS AND LIVER CANCER

An estimated 130–170 million people live with chronic HCV infection

worldwide, and an estimated 350,000 die of HCV-related liver disease

each year (Perz et al., 2006). There are about 2.3–4.7 million new HCV

infections each year from nosocomial transmission alone (Lavanchy, 2009).

Unsafe mass immunization has led to exceedingly high HCV prevalence in

some areas, such as Egypt, where 14–20% of the population has HCV anti-

bodies (Frank et al., 2000; Lavanchy, 2008). In most populations in Africa,

North America, South America, Europe, and Southeast Asia, the prevalence

in the general population is less than 3% (Lavanchy, 2008).

HCV is efﬁciently transmitted via direct percutaneous exposure to in-

fectious blood. Hepatitis C became a global epidemic in the 20th century as

blood transfusions, hemodialysis, and the use of injection needles to admin-

ister licit and illicit drugs increased throughout the world (Drucker et al.,

2001; Pybus et al., 2007). For example, the extremely high prevalence of

HCV in Egypt is due to a schistosomiasis-eradication campaign that began

in the 1960s, when more than 35 million injections were administered to

about 6 million Egyptians (Deufﬁc-Burban et al., 2006; Frank et al., 2000;

Lehman and Wilson, 2009). The identiﬁcation of the virus in 1989 led to

measures to reduce health-care–related exposure to HCV, particularly in

industrialized nations. However, more than six billion unsafe injections are

given worldwide each year (Hutin et al., 2003).

With the reduction in health-care–related exposures to HCV and the

recent introduction of the practice of illicit-drug injection in new regions

of the world, HCV infection through injection-drug use has become the

major source of exposure to HCV worldwide. Explosive increases in HCV

infection have occurred in regions of Asia and central and eastern Europe

because of poor access to sterile injection equipment and lack of drug

treatment. A recent meta-analysis reported that HCV prevalence was 84%

in injection-drug users (IDUs) surveyed in the Guangxi region bordering

the Golden Triangle in China (Xia et al., 2008). In that region, drug use

is highly stigmatized, which reduces community support for prevention ef-

forts and inhibits IDUs’ access to prevention services. Antiviral treatments

for chronic HBV and HCV infections can effectively reduce the associated

morbidity and mortality from liver disease. However, access to treatment

is often limited by high costs of care and by the asymptomatic nature of

chronic HBV and HCV infections. Therefore, many infected people are not

identiﬁed in time to beneﬁt from antiviral treatment.

Global eradication or elimination of new HBV infections is plausible

because the infections can be prevented with the hepatitis B vaccine. No

vaccine to prevent hepatitis C has been licensed. Given the limitations of

the scope of the committee’s work, it did not assess global prevention and

control efforts for hepatitis B and hepatitis C and did not consider the in-

ternational effects of its recommendations.

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INTRODUCTION 25

PREVALENCE AND INCIDENCE OF HEPATITIS B

AND HEPATITIS C IN THE UNITED STATES

HBV and HCV infections pose a major public-health problem in the

United States and are major causes of chronic liver disease. Three to ﬁve

times more people are living with chronic viral hepatitis infections than

with HIV infection. Table 1-2 presents the burden of HBV, HCV, and

HIV infections in the United States. The US Centers for Disease Control

and Prevention (CDC) estimates that 3.5–5.3 million people in the United

States—1–2% of the population—are living with chronic HBV or HCV

infection—about 800,000 to 1.4 million people with chronic hepatitis B

and an additional 2.7–3.9 million people with chronic hepatitis C (CDC,

2009d). However, an accurate estimate is difﬁcult to obtain because there

is no national chronic-hepatitis surveillance program. Each year, about

15,000 deaths are caused by HBV- or HCV-associated liver cancer or end-

stage liver disease (CDC, 2009d). Almost half the liver transplantations in

the United States are necessitated by end-stage liver disease associated with

HBV or HCV infection (Kim et al., 2009).

The annual costs of HBV and HCV infections are difﬁcult to determine.

The direct medical cost associated with HBV infection has been estimated

at $5.8 million based on the number of new cases in 2000 among persons

5–24 years old (Chesson et al., 2004). An estimated $1.8 billion in medical

care costs was associated with HCV infections in 1997 (Leigh et al., 2001).

Indirect costs, such as lost productivity, add to the HCV-associated cost

burden. Because of the aging of people now infected (including some people

with asymptomatic infections who will become symptomatic), HCV-related

illnesses, deaths, and costs are all expected to rise substantially during the

next two decades (Pyenson et al., 2009; Wong et al., 2000).

Hepatitis B

The national strategy for preventing new HBV infection in infants and

children—including routine screening of pregnant women for hepatitis

B surface antigen (a blood marker for chronic HBV infection), universal

infant hepatitis B immunization, and catchup vaccination of unvaccinated

children and adolescents—has resulted in a dramatic reduction in chronic

HBV infection in infants and acute HBV infection in children of all eth-

nicities (CDC, 2004; Mast et al., 2005, 2006). Despite those achievements,

the goal of eliminating perinatal HBV transmission has not been achieved,

largely because coverage of newborns with a birth dose of hepatitis B vac-

cine is incomplete (CDC, 2008c). As a result, CDC estimates that each year

about 1,000 newborns develop chronic HBV infection, which puts them at

risk for premature death from HBV-related liver disease (Ward, 2008b).

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TABLE 1-2 Burden of Selected Serious Chronic Viral Infections in the United States

Virus Prevalence

a,b

Percentage of

Population

Unaware

of Infection

Status

c,d,e

Deaths in 2006

Related to

Infection

a,b

Vaccine-

Preventable

Transmission

Routes

Percentage of CDC

NCHHSTP FY 2008

Budget

HBV 0.8–1.4 million About 65% 3,000 Yes Birth, blood, sex

2% combined

HCV 2.7–3.9 million About 75% 12,000 No Birth, blood, sex

HIV/AIDS 1.1 million About 21% 14,016 No Birth, blood, sex 69% (domestic

activities)

Abbreviations: CDC NCHHSTP, Centers for Disease Control and Prevention National Center for HIV/AIDS, Viral Hepatitis, Sexually Transmitted

Disease, and Tuberculosis Prevention; HBV, hepatitis B virus; HCV, hepatitis C virus; HIV/AIDS, human immunodeﬁciency virus/acquired immu-

nodeﬁciency syndrome.

SOURCES:

CDC, 2009b;

CDC, 2009d;

Lin et al., 2007;

Hagan et al., 2006;

CDC, 2008b;

Ward, 2008a.

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INTRODUCTION 27

Based upon surveillance data and modeling, CDC estimates that there

has been an 82% decline in incidence of acute HBV infection since 1990

with the total number of new infections in 2007 estimated at 43,000

(Daniels et al., 2009). Because many children have been vaccinated against

HBV, most reported cases of acute HBV infection are in adults. The national

strategy for preventing HBV transmission in adults—by recommending

hepatitis B vaccination selectively for high-risk adults (including men who

have sex with men, IDUs, and correctional-facility inmates)—has had only

little success in reducing the incidence of acute HBV infection in US adults

(Mast et al., 2006). Acute HBV infections are often asymptomatic or have

symptoms similar to those of other common illnesses, such as inﬂuenza, so

there is a high probability of underreporting.

In the United States, data on reported cases of acute HBV infection in

2007 indicate that the highest rate of infection is in non-Hispanic black

men: 2.3 per 100,000. The incidence is substantially lower in other popu-

lations: 0.9 per 100,000 Asians and Paciﬁc Islanders (APIs) and 1.0 per

100,000 non-Hispanic whites and Hispanics. There also appear to be geo-

graphic variations in incidence; the highest rates of acute HBV infection are

in the South

(Daniels et al., 2009).

Although the incidence of acute HBV infection is declining in the United

States, the number of people who are living with chronic HBV infection

may be increasing as a result of immigration from highly endemic countries

(that is, the hepatitis B surface antigen prevalence is ≥ 2%). On the basis

of immigration patterns in the last decade, it is estimated that every year

40,000–45,000 people enter the United States legally from HBV-endemic

countries (Mast et al., 2006; U.S. Department of Homeland Security, 2009).

Some populations are at higher risk for chronic HBV infection, including

API Americans, who make up only 4.5% of the general US population (U.S.

Census Bureau, 2008) but account for more than 50% of Americans who

are living with chronic HBV infection (CDC, 2009c). The prevalence of

chronic HBV infection in API Americans is as high as 15% in some studies

and constitutes an important health disparity (CDC, 2006). Having been

born in an HBV-endemic country appears to be the major risk factor for

chronic HBV infection in the API population (Lin et al., 2007).

Recent studies suggest that routine HBV testing of all adult API Ameri-

cans is cost-effective (Hutton et al., 2007), but almost two-thirds of chroni-

cally infected API Americans are unaware of their infection status because

they have not been tested for HBV (CDC, 2006; Lin et al., 2007).

CDC’s southern region includes Alabama, Arkansas, Delaware, the District of Columbia,

Florida, Georgia, Kentucky, Louisiana, Maryland, Mississippi, North Carolina, Oklahoma,

South Carolina, Tennessee, Texas, Virginia, and West Virginia.

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28 HEPATITIS AND LIVER CANCER

Hepatitis C

Persons likely to have chronic HCV infection include those who re-

ceived a blood transfusion before 1992 and past or current IDUs. US

veterans who use the Department of Veterans Affairs (VA) health-care sys-

tem have a higher prevalence of HCV infection (4–35%) than the general

population (about 2%) (Cheung, 2000; Dominitz et al., 2005; Groom et al.,

2008; Sloan et al., 2004), so VA has established a program to test all VA

patients for HCV infection and to manage HCV-positive patients clinically

(Kussman, 2007). As is the case with HBV infection, most patients who

have acute or chronic HCV infection are asymptomatic, and their disease

remains undiagnosed (Kamal, 2008).

In the United States, most IDUs have serologic evidence of HCV in-

fection, but the prevalence is highly variable. For example, in a study of

young IDUs in four US cities, the prevalence of HCV antibody was 35%

overall but varied from 14% in Chicago and 27% in Los Angeles to 51%

in Baltimore and New York City (Amon et al., 2008). Prevalence is strongly

associated with time engaged in risky behaviors, rising as the number of

years of drug-injecting accumulates and reaching 65–90% in longer-term

injectors (Hagan et al., 2008). HCV prevalence in IDUs in industrialized

nations has fallen in recent years. For example, in IDUs injecting for less

than 1 year, HCV prevalence fell from 46% before 1995 to 32% in a more

recent period and in IDUs injecting for 5 years or more, prevalence fell from

67% before 1995 to 53% in the period after 1995 (Hagan et al., 2008).

Most of the estimates of HCV incidence rates in IDUs in the United States

have been between 15 and 30 per 100 person years at risk, with higher

incidence found in recent-onset injectors (Garfein et al., 1998; Hagan et

al., 2001, 2008; Hahn et al., 2002; Maher et al., 2006; Smyth et al., 2000;

Thorpe et al., 2002).

The prevalence of HCV infection in the incarcerated population has

been reported to vary from 12% to 35% (Boutwell et al., 2005; Weinbaum

et al., 2003). Although some HCV transmission occurs within correctional

settings (Hunt and Saab, 2009; Macalino et al., 2004), the vast majority of

HCV-infected inmates became infected by injection-drug use in the com-

munity and not while incarcerated (Weinbaum et al., 2003).

Although reporting of acute HCV infection does not accurately reﬂect

the underlying incidence in the United States, the number of acute HCV

infections peaked in the late 1980s and declined throughout the 1990s

(Armstrong et al., 2006; Shepard et al., 2005). The decline observed in

the 1990s may reﬂect changes in IDUs’ behavior and practices, including

greater participation in needle-exchange programs (Wasley et al., 2008). It

is consistent with results of studies summarized previously that suggest that

HCV seroconversion rates in IDUs have declined since 1995 (Armstrong

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INTRODUCTION 29

et al., 2006; Shepard et al., 2005). The decline slowed and then leveled off

starting in 2003, and there was a slight increase in reported acute cases in

2006 (Wasley et al., 2008). Interpretation of those trends is complicated,

however, inasmuch as reporting is related to access to health care and di-

agnosis of acute infection; many IDUs, who often have limited access to

health care and no symptoms from infection, are not included in the trend

analysis.

LIVER CANCER AND LIVER DISEASE FROM CHRONIC

HEPATITIS B VIRUS AND HEPATITIS C VIRUS INFECTIONS

Both chronic HBV and HCV infections can lead to HCC, a type of liver

cancer, and liver disease (But et al., 2008; McMahon, 2004, 2008; Tan et

al., 2008). The two most important risk factors for HCC are chronic HBV

and HCV infections. As stated above, an estimated 78% of HCC cases and

57% of liver cirrhosis cases are caused by chronic HBV and HCV infections

(Perz et al., 2006).

In the United States, an estimated 3,000 people die each year from

HCC or chronic liver disease caused by HBV infection (CDC, 2008a).

However, risks of those outcomes vary and are higher in men and in people

who are older, ingest large amounts of alcohol, and are coinfected with HIV

(McMahon, 2004; Pungpapong et al., 2007). Outcomes of HBV infections

occur much more often in those with high blood concentrations of HBV

DNA, in persons over 40 years old, and in persons infected with HBV

genotype C (Chen et al., 2006; Dehesa-Violante and Nuñez-Nateras, 2007;

McMahon, 2004; Pungpapong et al., 2007). There are an especially high

prevalence of chronic HBV infection and a high risk of HCC in the API

American population, who make up the largest pool of chronically infected

persons in the United States and are most commonly infected with HBV

genotype C (Chang et al., 2007). HCC incidence tripled in the United States

from 1975 through 2005, and the highest incidence is in API Americans

who immigrated to the United States (Altekruse et al., 2009). American

Indian and Alaska Native peoples have been found to have the highest rate

of liver-related death of ethnic groups in the United States (Vong and Bell,

2004). The age-speciﬁc rate of death in American Indian and Alaska Native

peoples due to chronic liver disease is much higher than that in any other

population and chronic HBV infection and increasing rates of chronic HCV

infection play a large role (Vong and Bell, 2004).

In the United States, about 12,000 people die from complications of

chronic hepatitis C each year (CDC, 2008a). Deaths related to hepatitis

C have increased; the highest number of deaths are in middle-aged men,

non-Hispanic blacks, and American Indians (Wise et al., 2008). As is the

case with chronic hepatitis B, complications occur more often in men and

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30 HEPATITIS AND LIVER CANCER

in people who are older, have metabolic syndrome secondary to obesity,

ingest large amounts of alcohol, and are coinfected with HIV (Ghany et

al., 2009; Missiha et al., 2008; Pradat et al., 2007). There are also impor-

tant ethnic and racial differences in the burden of chronic hepatitis C. The

prevalence of HCV infection is higher in blacks than in whites (Armstrong

et al., 2006; Thomas et al., 2000). Blacks also are less likely to respond

to interferon-alpha-based treatment for chronic hepatitis C; this seems to

be explained to a large extent by differences in DNA sequences near the

interferon lambda 3 gene (Ge et al., 2009; Jeffers et al., 2004; Muir et al.,

2004; Thomas et al., 2009). Likewise, there appears to be a greater burden

of chronic hepatitis C and reduced response to treatment in Hispanic whites

than in non-Hispanic whites (Armstrong et al., 2006; Bonacini et al., 2001;

Rodriguez-Torres et al., 2009). In both Hispanics and blacks, HCC risk is

increasing, in large part because of chronic hepatitis C (Altekruse et al.,

2009). However, there is less evidence than in the case of HBV infection

that different HCV genotypes or higher blood HCV concentrations increase

the risk of long-term disease outcomes. Health-care use trends from 1994

to 2001 show a 20–30% yearly increase in HCV-related hospitalizations,

length of hospital stays, total hospitalization costs, and hospital deaths

(Grant et al., 2005).

THE COMMITTEE’S TASK

CDC has developed recommendations for the prevention and control of

hepatitis B (Mast et al., 2005, 2006; Weinbaum et al., 2008) and hepatitis C

(CDC, 1998, 2001). The National Institutes of Health (NIH) has developed

consensus documents on the management of hepatitis B (NIH, 2008) and

hepatitis C (NIH, 2002). WHO has published guidelines related to hepatitis

B vaccination of children (WHO, 2001). A number of not-for-proﬁt organi-

zations have also worked to increase awareness of the diseases, educate the

public about prevention, and advocate for those chronically infected with

HBV and HCV. Although government and nongovernment efforts have

led to a decline in the number of cases, chronic hepatitis B and hepatitis C

continue to be serious public-health problems in the United States. For that

reason, CDC in conjunction with the National Viral Hepatitis Roundtable,

a not-for-proﬁt coalition of public, private, and voluntary organizations;

the Department of Health and Human Services Ofﬁce of Minority Health;

and VA sought guidance from the Institute of Medicine (IOM) in identi-

fying missed opportunities related to the prevention and control of HBV

and HCV infections. IOM was asked to focus on hepatitis B and hepatitis

C because they are common in the United States and can lead to chronic

disease. This report does not address hepatitis A virus, hepatitis E virus, or

hepatitis D virus (also called the hepatitis delta virus) infections.

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INTRODUCTION 31

The speciﬁc charge to the committee follows:

The IOM will form a committee to determine ways to reduce new HBV

and HCV infections and the morbidity and mortality related to chronic

viral hepatitis. The committee will assess current prevention and con-

trol activities and identify priorities for research, policy, and action. The

committee will highlight issues that warrant further investigations and

opportunities for collaboration between private and public sectors. In

conducting its work, the committee might want to consider:

Strategies for preventing new HBV and HCV infections:

• Improving vaccine coverage among vulnerable populations to reach

national transmission elimination goals.

• Increasing the proportion of persons aware of their chronic infection

status.

• Identifying barriers to the identiﬁcation, counseling, and testing of

persons at risk for chronic hepatitis, and ways they can be reduced

and eliminated.

• Promoting prevention among adolescents and adults who engage in

risky behaviors, particularly those known to have screened positive for

HCV and HBV infection.

• Determining optimal ways to identify, develop, and implement preven-

tion programs among at-risk populations.

• Development of an effective HCV vaccine.

Strategies for reducing morbidity and mortality from chronic HBV and

HCV infections:

• Providing appropriate medical referral, evaluation, and management of

chronically infected persons.

• Assessing health-care utilization and outcomes for persons with chronic

infections, and opportunities for prevention and care to reduce health-

care-related costs.

• Reducing health disparities in morbidity and mortality from viral

hepatitis.

• Improving clinical surveillance of markers of disease progression and

stage of hepatocellular carcinoma associated with chronic viral hepatitis

and associated cirrhosis.

Assess the type and quality of data needed from state and local viral hepa-

titis surveillance systems to guide and evaluate prevention services:

• Assess the role of acute disease surveillance in monitoring new infec-

tions, detecting outbreaks, identifying vaccine failures and documenting

the elimination of HBV transmission.

• Assess the role of state and local chronic disease surveillance in describ-

ing the burden of morbidity and mortality related to chronic hepatitis

B and hepatitis C and related liver cirrhosis and cancer, the extent of

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32 HEPATITIS AND LIVER CANCER

ongoing risk behaviors, and the impact of HIV co-infection and other

cofactors.

• Assess the role of state and local disease registries in the delivery of

prevention and care services for persons with chronic hepatitis B and

persons with hepatitis C.

• Assess the role of laboratory testing strategies for the identiﬁcation of

markers for acute HCV infection.

• Assess laboratory testing strategies for identiﬁcation of antiviral resis-

tance for HBV and HCV.

Finally, the committee should pay attention to addressing the special needs

of speciﬁc subpopulations at high risk, such as Asian Americans, African

Americans, and persons born in HBV-endemic countries.

THE COMMITTEE’S APPROACH TO ITS TASK

To address its charge, the committee ﬁrst reviewed available evidence on

a variety of topics related to the prevention of hepatitis B and hepatitis C,

management of these diseases, and surveillance activities related to viral

hepatitis. The evidence was drawn from the published literature and from

open-session presentations by recognized experts in the ﬁeld (see Appen-

dix B). Oral testimony presented by members of the public during the open

sessions was also taken into account. Additional information was obtained

from written testimony submitted to the committee (available from the

National Academies’ Public Access Records Ofﬁce, public[email protected]du).

A comprehensive review and evaluation of treatments for HBV and

HCV infections (for example, which medications to use) is beyond the

scope of this report. However, treatment information can be found in guide-

lines published by the American Association for the Study of Liver Diseases

(Ghany et al., 2009; Lok and McMahon, 2009) and in NIH consensus

statements on the management of hepatitis B (NIH, 2008) and hepatitis C

(NIH, 2002).

The committee also has not been tasked with comprehensively review-

ing information about the safety of the hepatitis B vaccine. Safety issues

surrounding this vaccine were reviewed in the IOM report Immunization

Safety Review: Hepatitis B Vaccine and Demyelinating Neurological Dis-

orders (IOM, 2002). The committee that wrote that report concluded that

the evidence favored rejection of a causal relationship between hepatitis B

vaccine administered to adults and incident multiple sclerosis and multiple-

sclerosis relapse. It also found the evidence inadequate for accepting or

rejecting a causal relationship between hepatitis B vaccine and the ﬁrst

episode of a central nervous system demyelinating disorder, acute dissemi-

nated encephalomyelitis, optic neuritis, transverse myelitis, Guillain-Barré

syndrome, or brachial neuritis. IOM has undertaken another review of the

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INTRODUCTION 33

safety of the hepatitis B vaccine, and the ﬁndings are expected to be avail-

able in 2011.

The committee that wrote the present report met ﬁve times in the period

December 2008–August 2009. During the meetings, the committee evalu-

ated the evidence and deliberated on issues relevant to its charge. Types of

evidence taken into consideration included international, federal, state, and

community guidelines, programs, and other activities aimed at preventing

new cases of HBV and HCV infection, identifying chronic cases of hepa-

titis B and hepatitis C, and managing those cases. It also explored federal

and state surveillance mechanisms for identifying and tracking hepatitis B

and hepatitis C cases. The committee began by identifying problems with

and gaps in the current prevention and control systems. It also examined

model programs for other infectious diseases, such as those covered under

the Ryan White CARE Act (Health Resources and Services Administration,

2009). The committee developed evidence-based recommendations to ad-

dress the problems with the current systems to reduce the numbers of new

HBV and HCV infections, to manage the care of chronically infected people

more effectively by reducing morbidity and mortality, and to improve sur-

veillance of chronic hepatitis B and hepatitis C cases.

The committee focused on making recommendations that could be

implemented with existing knowledge and available tools to advance pre-

vention and control of chronic viral hepatitis in a timely manner. Although

the committee recognizes the importance of basic research in this ﬁeld,

it believes that given the scope of the problem and the lack of available

resources, its focus should be on improving prevention and control ser-

vices. As a result, the committee did not address basic-research questions

in the ﬁeld extensively. Nor did it conduct cost–beneﬁt analyses of its

recommendations.

The committee’s general approach is presented in Figure 1-2. After

deﬁning the scope of the problem and reviewing the available evidence,

the committee identiﬁed the primary underlying factors that impede cur-

rent efforts to prevent and control hepatitis B and hepatitis C. The com-

mittee believes that a lack of awareness about viral hepatitis among both

the general public and health-care and social-service providers is leading

to continued high rates of morbidity and mortality from hepatitis B and

hepatitis C. Consistent themes were found in all the materials reviewed

by the committee; as a result, this report is organized according to four

principal categories:

• Improved disease surveillance (Chapter 2).

• Improved knowledge and awareness on the part of health-care and

social-service providers and the public (Chapter 3).

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FIGURE 1-2 The committee’s approach to its task.

The Problem

• 0.8–1.4 million people are chronically infected with hepatitis B virus (HBV) in United States

— 3,000 deaths each year are due to hepatitis B-related liver disease

• 2.7–3.9 million people are chronically infected with hepatitis C virus (HCV) in United States

— 12,000 deaths each year are due to hepatitis C-related liver disease

• Over 150,000 deaths due to hepatitis B and hepatitis C are projected to occur in next 10 years

Underlying issues

Lack of Public Awareness Lack of Provider Awareness

Lack of Public Resource Allocation

Consequences

• At-risk people do not know that they are at risk or how to prevent becoming infected

• At-risk people may not have access to preventive services

• Chronically infected people do not know that they are infected

• Many medical providers do not screen people or know how to manage those infected

• Infected people often have inadequate access to testing and medical management

• Inadequate disease-surveillance systems underreport both acute and chronic infections

Recommendations

Improved Disease

Surveillance

Improved Provider and

Community Education

Integration and Enhancement

of Viral Hepatitis Services

Outcomes

• Screening is widely used as a part of good primary care

• At-risk people and communities actively seek testing, preventive services, and appropriate medical management

• Better information leads to

— Improved understanding of hepatitis B and hepatitis C

— More effective and targeted prevention programs

— More research on effective vaccination and treatment options

• Infected people have better health outcomes

• Decreased transmission leads to fewer carriers of HBV and HCV and fewer cases of hepatitis B and hepatitis C

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INTRODUCTION 35

• Increased hepatitis B vaccination rates in various populations

(Chapter 4).

• Improved integration and enhancement of viral hepatitis services

for speciﬁc at-risk populations and in health-care and other settings

(Chapter 5).

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Surveillance

ublic-health surveillance is an essential tool in the prevention and con-

trol of infectious and chronic diseases and the medical management of

people who have the diseases. Surveillance data are used to estimate

the magnitude of a health problem, to describe the natural history of a

disease, to detect epidemics, to document the distribution and spread of a

health event or disease, to evaluate control and prevention measures, and

to aid in public-health planning (Thacker, 2000). Public-health surveillance

requires standardized, systematic, continuing collection and management

of data. In addition, surveillance should encompass timely analysis and

dissemination to allow public-health action (CDC, 2001a; Thacker, 2000).

Through those steps, federal agencies and state and local health depart-

ments are able to inform stakeholders by providing reliable information

that can be used to reduce morbidity and mortality through public policy,

appropriate resource distribution, and programmatic and educational inter-

ventions. The committee has deﬁned (see Box 2-1) the role of surveillance

for hepatitis B virus (HBV) and hepatitis C virus (HCV) that is within the

scope of its study.

This chapter describes how surveillance data are used or could be used

to determine the focus and scope of viral hepatitis prevention and control

efforts. The committee reviewed the weaknesses of the current surveillance

system for hepatitis B and hepatitis C, including the timeliness, accuracy,

and completeness of data collection, analysis, and dissemination. It found

that there were few published sources of information about viral hepatitis

surveillance. To obtain a clearer picture of the activities that were taking

place at state and local levels, the committee gathered information from

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various sources. Its ﬁndings are based on its review of the literature and on

information gathered through surveys of and direct contact with profes-

sionals working in this ﬁeld.

Much of the information gathered through surveys involved state-level

and city-level public-health department staff who were working on programs

funded by the Centers for Disease Control and Prevention (CDC). Forty-

nine states have a cooperative agreement with CDC that funds a coordina-

tor who conducts viral-hepatitis prevention activities, such as health-care

provider and consumer education, integration of viral-hepatitis prevention

services into health-care and public-health settings, and development of

state viral-hepatitis prevention plans. Although the cooperative agreements

do not include funds for viral-hepatitis surveillance, the coordinators are

good sources of information about surveillance activities being conducted

in each jurisdiction. CDC’s Division of Viral Hepatitis (DVH) performed a

brief survey of the CDC-funded hepatitis C coordinators in 2006 to gather

information about viral-hepatitis surveillance activities. At the request of

the committee, CDC again surveyed the coordinators (now called adult

viral-hepatitis prevention coordinators, AVHPCs) in April 2009. As part of

a national assessment of viral-hepatitis surveillance initiatives, the National

BOX 2-1

Role of Disease Surveillance

1. Identify acute hepatitis B virus (HBV) and hepatitis C virus (HCV)

outbreaks and individual acute cases and measure incidence

 • Respond to outbreaks by

  o Identifying cases

  o Mobilizing appropriate resources to provide preventive services

to eliminate or minimize further transmission

 • Develop accurate estimates of the burden of acute hepatitis B and

hepatitis C in United States

2. Identify chronic cases of hepatitis B and C and measure prevalence

 • Develop accurate estimates of the burden of chronic disease in

United States

 • Prevent secondary cases

  o Hepatitis B: Education, vaccination, and screening

  o Hepatitis C: Education, harm reduction, and screening

3. Link cases to appropriate services, including medical management

4. Evaluate current practices and prevention efforts

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Alliance of State and Territorial AIDS Directors interviewed staff involved

in enhanced viral-hepatitis surveillance projects funded through CDC’s

Emerging Infections Programs early in 2009 (the programs are described

in more detail later in this chapter). Committee members also contacted

several AVHPCs directly in April and May 2009 to discuss their work.

The recommendations for surveillance based on the committee’s ﬁnd-

ings focus on the development of a model designed to improve the quality

and accuracy of information by developing systems to collect, analyze,

and disseminate data on acute and chronic HBV and HCV infections. The

recommendations call for a two-part system: core surveillance activities,

building the capacity of state and local health departments to conduct

standard disease surveillance on newly diagnosed acute and chronic HBV

and HCV infections, and targeted surveillance to obtain data on speciﬁc

populations that are not represented fully in the collection of core surveil-

lance data. Core surveillance means those activities in which all jurisdic-

tions must engage to provide accurate, complete, and timely information to

monitor incidence, prevalence, and trends in disease diagnoses. Data from

other activities, such as targeted surveillance, supplement information from

core surveillance, and are necessary to provide accurate incidence estimates,

given the challenges of conducting hepatitis B and C surveillance, as de-

tailed in this chapter. The recommendations also include guidance regarding

the interpretation and dissemination of surveillance data.

APPLICATIONS OF SURVEILLANCE DATA

Surveillance data are used in a variety of ways by a broad base of

state health-department staff, researchers, clinicians, policy-makers, and

private industry. Federal and state health-department surveillance systems

provide population-based information that can be used to improve the

public’s health. They also offer an opportunity for public-health interven-

tion at the individual level by linking infected people to appropriate care

and support services (Klevens et al., 2009). Overall, surveillance data are

critical in estimating incidence and prevalence of HBV and HCV infections

(CDC, 2008c), and they provide a basis for studying and understanding the

mechanisms of diverse outcomes in the natural history of these infections

(Thacker, 2000).

Public health surveillance generally involves name-based reporting of

cases of speciﬁed diseases to state and local health departments. As such,

it requires the gathering of information that some people consider private.

Public health ofﬁcials and state legislatures have weighed the costs and

beneﬁts of public health surveillance and have required name-based report-

ing of speciﬁc diseases with conﬁdentiality safeguards in place to protect

private information (Fairchild et al., 2008). Conﬁdential name-based re-

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porting is standard practice for infectious diseases surveillance, including

HIV surveillance (CDC, 2008d). Acute HBV infections are reportable in

all states and acute HCV infections are reportable in all but one state. All

states report the cases to CDC. Chronic HBV infections are reportable in

all but six states and chronic HCV infections are reportable in all but seven

states (CSTE, 2009).

Outbreak Detection and Control

Accurate and timely surveillance data are necessary to identify out-

breaks of acute HBV and HCV infection in the health-care and community

settings. The data can assist in recognizing and addressing breaches in in-

fection control, and they can help to mitigate the size of outbreaks. There

have been several outbreaks of hepatitis B and hepatitis C in health-care

settings in recent years (CDC, 2003b, 2003d, 2005b, 2008a, 2009c; Fabrizi

et al., 2008; Thompson et al., 2009). Research on those outbreaks has

shown that they typically occurred in dialysis units, medical wards, nursing

homes, surgery wards, and outpatient clinics and resulted from breaches in

infection control (Lanini et al., 2009). In a 2009 study, researchers found

evidence of 33 outbreaks in nonhospital health-care settings in the United

States in the last 10 years. Transmission was primarily patient to patient

and was caused by lapses in infection control and aseptic techniques that

allowed contamination of shared medical devices, such as dialysis machines.

The authors stated that successful outbreak control depended on systematic

case identiﬁcation and investigation, but most health departments did not

have the time, funds, personnel resources, or legal authority to investigate

health-care–associated outbreaks (Thompson et al., 2009).

Hepatitis B and hepatitis C surveillance data can be used to identify or

quantify new trends in the transmission of HBV and HCV. For example,

surveillance data can help epidemiologists to determine whether sexual

transmission of HCV reported among some cohorts of HIV-positive men

who have sex with men (Matthews et al., 2007; van de Laar et al., 2009)

is statistically signiﬁcant on a population level. Surveillance data have also

been used to identify clusters of newly acquired cases of hepatitis C in ado-

lescents and young adults and to direct appropriate interventions to persons

in the clusters (CDC, 2008f). Those ﬁndings can help public-health ofﬁcials

to target their resources at emerging populations being affected by HBV and

HCV, such as racial and ethnic populations or geographically linked active

injection-drug users (IDUs).

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Resource Allocation

Surveillance data are often used to determine how to use resources most

effectively. For example, estimates of disease burden are commonly used

to provide guidance to policy-makers on the level of funding required for

disease-related programs. If surveillance data are not available or understate

the disease burden, legislators and public-health ofﬁcials will not allocate

sufﬁcient resources to mount an appropriate public-health response.

Information on disease burden is only one factor that guides policy-

makers in allocating public-health resources. Priorities in public funding

are also driven by public awareness and advocacy. Therefore, it is im-

portant to communicate surveillance trends and disease burden clearly to

policy-makers and community advocates. For example, estimates of trends

indicate that mortality from HCV may soon exceed that from HIV (Deufﬁc-

Burban et al., 2007). However, despite the large number of individuals and

communities affected by hepatitis B and hepatitis C, the resources available

for addressing viral hepatitis are only a small fraction of those available

for addressing HIV. CDC’s National Center for HIV/AIDS, Viral Hepatitis,

Sexually Transmitted Diseases, and Tuberculosis Prevention had a budget

of almost $1 billion for 2008, and only 2% of it was allocated to hepatitis

B and hepatitis C (Ward, 2008). Sixty-nine percent of the budget was al-

located for HIV, 15% for sexually transmitted diseases (STDs), and 14%

for tuberculosis.

Programmatic Design and Evaluation

Public-health organizations use surveillance data to design programs

that target appropriate populations. For example, CDC requires states to

set priorities among populations for HIV prevention according to data

generated by HIV/AIDS surveillance programs and community-services

assessments (CDC, 2003a). Surveillance data can also be used to evaluate

systems for delivery of prevention and care service. A key potential role of

hepatitis surveillance programs is to evaluate the effect of HBV vaccination

programs (Wasley et al., 2007).

Linking Patients to Care

For some diseases, it is desirable to have a surveillance system closely

involved in ensuring the linkage of persons who have new diagnoses to

health-care services, often called case management (Fleming et al., 2006).

For viral-hepatitis surveillance, linking patients who have recent diagnoses

to comprehensive viral-hepatitis programs may be indicated to ensure ac-

cess to appropriate services, including clinical evaluation, regular followup

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46 HEPATITIS AND LIVER CANCER

visits, referral to drug-treatment and harm-reduction programs, education

about liver health, and prevention of transmission to others. Chapter 5 will

discuss the components of viral-hepatitis services.

DISEASE-SPECIFIC ISSUES RELATED TO

VIRAL-HEPATITIS SURVEILLANCE

Many of the difﬁculties that surveillance systems face in identifying and

tracking cases of hepatitis B and hepatitis C are related to the complexity

of the infections and their associated progression (see Figures 2-1 and 2-2).

This section highlights some of those challenges. Chapter 5 will provide

more detail on issues related to screening and identiﬁcation.

Figure 2-1, fixed image

FIGURE 2-1 Natural progression of hepatitis B infection.

Abbreviations: HBeAg, hepatitis B e antigen; anti-HBe, antibody to hepatitis B e

antigen; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; HCC, hepato-

cellular carcinoma.

Transmission occurs in 90% of infants of HBsAg+/HBeAg+ mothers and 15%

of infants of HBsAg+/anti-HBe+ mothers.

30% of those infected from the age of 1–5 years and under 7% of those infected

at the age of 6 years or older.

About 50% of patients by 5 years and 70% of patients by 10 years will sero-

convert to anti-HBe.

15-25% risk of premature death from cirrhosis and HCC.

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Identifying Acute Infections

Several factors contribute to the difﬁculty in identifying acute HBV

and HCV infections. Many newly acquired cases are asymptomatic, or

they may have symptoms similar to those of other common illnesses and

so do not prompt health-care providers to conduct serologic testing for

HBV and HCV, or the serologic tests that are conducted are inadequate

to distinguish between acute and chronic cases. About 90% of acute HBV

infections in children under 5 years of age and 70% of HBV infections in

adults are asymptomatic (McMahon et al., 1985); 75–95% of acute HCV

infections are asymptomatic (Chen and Morgan, 2006; Guerrant et al.,

2001), so few infected patients seek care for the acute illness; and there

is a very high probability of underreporting even when care is obtained

(Chen and Morgan, 2006; Cox et al., 2005; Hagan et al., 2002). Clinicians

Figure 2-2, fixed image

FIGURE 2-2 Natural progression of hepatitis C infection.

Abbreviations: HCV, hepatitis C virus; RNA, ribonucleic acid; HCC, hepatocellular

carcinoma.

SOURCE: Adapted from Chen and Morgan, 2006. Reprinted with permission from

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48 HEPATITIS AND LIVER CANCER

often are not fully aware of reporting requirements in connection with

other reportable diseases and do not initiate reports routinely (Allen and

Ferson, 2000). In addition, some persons with chronic HBV infection can

experience sudden increases in alanine aminotransferase (ALT) that may be

associated with jaundice or liver decompensation. That change may have a

variety of causes, including infection with another hepatitis virus; alcohol,

drug, or medication use; or sudden hepatitis B disease reactivation that can

be associated with the period of seroconversion from a hepatitis B e antigen

(HBeAg) state to an antibody to hepatitis B e (anti-HBe) state or reversion

from an anti-HBe state back to an HBeAg-positive state (Koff, 2004).

Therefore, in investigating acute symptomatic infections, it is important

to identify outbreaks so that preventive measures can be undertaken and,

in the case of hepatitis B, to identify and screen close contacts who might

beneﬁt from the hepatitis B vaccine. Such information is needed if surveil-

lance staff is to determine which cases are newly diagnosed, the result of

recent exposure, or chronic (Fleming et al., 2006).

Classifying acute cases of hepatitis B and hepatitis C requires a complex

integration of clinical data, positive and negative laboratory data, and prior

or repeat testing (see Boxes 2-2 and 2-3). Many of the test results—for

BOX 2-2

CDC Acute Hepatitis B Case Definition

Clinical case deﬁnition:

An acute illness with

• discrete onset of symptoms

and

• jaundice or elevated serum aminotransferase levels

Laboratory criteria for diagnosis:

• IgM antibody to hepatitis B core antigen (anti-HBc) positive

• hepatitis B surface antigen (HBsAg) positive

• IgM anti-HAV negative (if done)

Case classiﬁcation:

Conﬁrmed: a case that meets the clinical case deﬁnition and is labora-

tory conﬁrmed

Abbreviations: CDC, Centers for Disease Control and Prevention; HAV, hepatitis A virus; HBV,

hepatitis B virus.

SOURCE: CDC, 2009a.

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BOX 2-3

CDC Acute Hepatitis C Case Definition

Clinical case deﬁnition:

An acute illness with a discrete onset of any sign or symptom consistent

with acute viral hepatitis (e.g., anorexia, abdominal discomfort, nausea,

vomiting), and either jaundice or serum alanine aminotransferase (ALT)

levels >400 IU/L.

Laboratory criteria for diagnosis:

One or more of the following three criteria:

1) Antibodies to hepatitis C virus (anti-HCV) screening test positive

with a signal to cut-off ratio predictive of a true positive as determined

for the particular assay as deﬁned by CDC, OR

2) Hepatitis C Virus Recombinant Immunoblot Assay (HCV RIBA)

positive, OR

3) Nucleic Acid Test (NAT) for HCV RNA positive

and, meets the following two criteria:

1) IgM antibody to hepatitis A virus (IgM anti-HAV) negative, AND

2) IgM antibody to hepatitis B core antigen (IgM anti-HBc) negative

Case classiﬁcation:

Conﬁrmed: A case that meets the clinical case deﬁnition, is laboratory

conﬁrmed, and is not known to have chronic hepatitis C.

Abbreviations: CDC, Centers for Disease Control and Prevention; HAV, hepatitis A virus; HCV,

hepatitis C virus; RIBA, recombinant immunoblot assay; RNA, ribonucleic acid.

NOTE: URL for the signal-to-cutoff ratios: http://www.cdc.gov/ncidod/diseases/hepatitis/c/

sc_ratios.htm.

SOURCE: CDC, 2009a.

example, for ALT, aspartate transaminase, immunoglobulin M (IgM) an-

tibody to the hepatitis A virus, and IgM antibody to the hepatitis B core

antigen (HBcAg)—are difﬁcult for health departments to obtain, particu-

larly because negative test results often are not automatically reported to

health departments (Fleming et al., 2006). Because auxiliary test results are

not systematically reported to health departments, surveillance staff must

actively follow up with health-care providers to obtain them and other

clinical indicators of acute disease. If the data cannot be obtained, either

because the proper tests were not ordered or because there is insufﬁcient

staff to conduct followup, cases will be classiﬁed ambiguously as nonacute

infections.

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Furthermore, current CDC case deﬁnitions may miss a substantial frac-

tion of clinically apparent acute cases because they lack clinical markers

that could improve case identiﬁcation and help to distinguish between acute

and chronic cases. Using data from electronic medical records, Klompas et

al. (2008) found that CDC’s case deﬁnition of acute HBV had a positive

predictive value of only 47.2% (that is, out of 1,000 people identiﬁed as

having acute hepatitis B with the CDC case deﬁnition, only 472 of them

were found to truly have acute hepatitis B). When patients with prior

positive tests for HBV infection (or International Classiﬁcation of Diseases,

revision 9, codes for chronic HBV infection) were excluded, the positive

predictive value increased to 68.4%. However, the positive predictive value

was raised to above 96% by adding the requirement for peak ALT over

1,000 or total bilirubin over 1.5. Most important, when applying the most

sensitive algorithm (the algorithm that detected the greatest number of

cases of acute hepatitis B), the study found that only four of the eight cases

of acute hepatitis B were in the state’s surveillance system and only one of

the four was correctly classiﬁed as acute; this suggests that 88% of acute

hepatitis B cases may be missed if current reporting algorithms are used

(Klompas et al., 2008).

Similarly, detection of acute hepatitis C can be challenging because no

single case deﬁnition is either sensitive or speciﬁc for it. HCV seroconver-

sion may be missed, and there is no IgM-based assay that reliably distin-

guishes acute hepatitis C from chronic hepatitis C, unlike the situation with

hepatitis A virus or HBV infection. Relatively low HCV ribonucleic acid

(RNA) concentrations and more than one log ﬂuctuation in HCV RNA

concentration are features of acute HCV infection that may be useful for

the development of more dynamic diagnostic algorithms, but the accuracy

of these algorithms has not been validated (Cox et al., 2005; McGovern et

al., 2009; Villano et al., 1999).

In summary, the identiﬁcation of acute hepatitis infection is inherently

ﬂawed because the vast majority of cases are asymptomatic and patients

do not seek medical care or testing. Such persons would be identiﬁed only

in prospective studies that include routine serial testing of liver enzyme

concentrations, such as those previously conducted to identify the incidence

of transfusion-associated hepatitis. Underreporting of diagnosed cases and

misclassiﬁcation of reported cases seriously limit the accuracy of data on

cases of acute viral hepatitis collected by state and territorial surveillance

programs and transmitted to CDC. Thus, the estimates of the incidence of

acute hepatitis in the United States are based solely on symptomatic cases.

The majority of those cases may be missing from the surveillance system

because of poor access to health care, underreporting, and misclassiﬁca-

tion. Taken together, published surveillance summaries of reported cases of

acute viral hepatitis substantially underestimate the number of cases; these

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summaries may give misleading impressions of the incidence of disease to

policy-makers and program planners.

Identifying Chronic Infections

Given that both hepatitis B and hepatitis C infections are largely

asymptomatic, most people do not receive a diagnosis until the infection is

chronic. For hepatitis B, the chance of developing a chronic infection varies

with age at the time of infection.

In persons over 6 years old, the vast majority of acute HBV infections

are self-limited (Hyams, 1995). However, hepatitis B infections become

chronic in over 90% of infants who are infected at birth or in the ﬁrst year

of life and in 30% of children who are infected at the age of 1–5 years

(Pungpapong et al., 2007). Although hepatitis B surface antigen (HBsAg)

is detectable within 4–10 weeks after infection, it is indicative of chronic

HBV infection only if it persists for more than 6 months (Koff, 2004). An

accurate diagnosis of chronic hepatitis B may therefore require the report-

ing of multiple serologic markers at more than one time (Koff, 2004).

For disease-surveillance purposes, it can be challenging for health de-

partments to obtain the complete laboratory results that are necessary to

classify a chronic hepatitis B case according to CDC’s case deﬁnitions (see

Box 2-4). In general, a full hepatitis B panel (including any negative results

for IgM anti-HBc) is required or two HBsAg results at least 6 months

apart. Although states govern laboratory-reporting requirements in their

jurisdictions, negative test results are generally not reportable and must be

actively obtained. CDC’s Guidelines for Viral Hepatitis Surveillance and

Case Management recommend that only positive HBsAg-test results be

reported, but this test alone is inadequate to distinguish acute from chronic

infection. Automated systems attached to electronic medical records may

help to address surveillance for chronic HBV cases in the future, but in the

meantime many diagnoses of chronic HBV infection probably will not be

correctly captured and classiﬁed as conﬁrmed cases (CDC, 2005a).

Surveillance for chronic HCV infection also presents challenges (see

Box 2-5). In adults, about 15–25% of acute hepatitis C infections resolve

spontaneously (Villano et al., 1999). That may increase to about 45% in

children and young adults (Vogt et al., 1999). The presence of HCV RNA

is generally detected within 1 week of infection (Mosley et al., 2005), but

antibodies to HCV (anti-HCV) can be detected in only 50–70% of infected

persons at the onset of symptoms; this increases to more than 90% after 3

months (NIH, 2002). A chronic infection is characterized by the persistent

presence of HCV RNA for at least 6 months (NIH, 2002).

Typically, when a patient presents for HCV testing, the ﬁrst test that

is conducted is for the presence of anti-HCV. This test is generally an en-

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BOX 2-4

CDC Chronic Hepatitis B Case Definition

Clinical description

Persons with chronic HBV infection may have no evidence of liver dis-

ease or may have a spectrum of disease ranging from chronic hepa-

titis to cirrhosis or liver cancer. Persons with chronic infection may be

asymptomatic.

Laboratory criteria

• IgM antibodies to anti-HBc negative

and

• a positive result on one of the following tests: hepatitis B surface an-

tigen HBsAg, HBeAg, or hepatitis B virus (HBV) DNA,

• HBsAg positive or HBV DNA positive or HBeAg positive two times

at least 6 months apart (Any combination of these tests performed 6

months apart is acceptable.)

Case classiﬁcation

Conﬁrmed: a case that meets either laboratory criteria for diagnosis

Probable: a case with a single HBsAg positive or HBV DNA positive or

HBeAg positive lab result when no IgM anti-HBc results are available

Comment

Multiple laboratory tests indicative of chronic HBV infection may be

performed simultaneously on the same patient specimen as part of a

“hepatitis panel.” Testing performed in this manner may lead to seemingly

discordant results, e.g., HBsAg-negative and HBV DNA-positive. For

the purposes of this case deﬁnition, any positive result among the three

laboratory tests mentioned above is acceptable, regardless of other test-

ing results. Negative HBeAg results and HBV DNA levels below positive

cutoff level do not conﬁrm the absence of HBV infection.

Abbreviations: CDC, Centers for Disease Control and Prevention; anti-HBc, hepatitis B core

antigen; HBsAg, hepatitis B surface antigen; HBeAg, hepatitis B e antigen; HBV, hepatitis B

virus; DNA, deoxyribonucleic acid.

SOURCE: CDC, 2009a.

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BOX 2-5

CDC Hepatitis C Virus Infection Case Definition

(Past or Present)

Clinical description:

Most HCV-infected persons are asymptomatic. However, many have

chronic liver disease, which can range from mild to severe including cir-

rhosis and liver cancer.

Laboratory criteria for diagnosis:

• Anti-HCV positive (repeat reactive) by EIA, veriﬁed by an additional

more speciﬁc assay (e.g., RIBA for anti-HCV or nucleic acid testing

for HCV RNA),

• HCV RIBA positive,

• Nucleic acid test for HCV RNA positive,

• Report of HCV genotype,

• Anti-HCV screening-test-positive with a signal to cut-off ratio predic-

tive of a true positive as determined for the particular assay (e.g., ≥3.8

for the enzyme immunoassays) as determined and posted by CDC.

Case classiﬁcation:

Conﬁrmed: a case that is laboratory conﬁrmed and that does not meet

the case deﬁnition for acute hepatitis C.

Probable: a case that is anti-HCV positive (repeat reactive) by EIA and

has ALT or SGPT values above the upper limit of normal, but the anti-

HCV EIA result has not been veriﬁed by an additional more speciﬁc

assay or the signal to cutoff ratio is unknown.

Abbreviations: CDC, Centers for Disease Control and Prevention; HCV, hepatitis C virus; EIA,

enzyme immunoassay; RIBA, recombinant immunoblot assay; RNA, ribonucleic acid; ALT or

SGPT, alanine aminotranferase.

SOURCE: CDC, 2009a.

zyme immunoassay (EIA). A repeatedly reactive EIA is followed by a more

speciﬁc assay to detect viremia, such as the recombinant immunoblot assay

(RIBA) for anti-HCV, or by nucleic acid testing for HCV RNA. In some

cases, an EIA with a high signal-to-cutoff ratio predictive of a true positive

will be used in the place of a conﬁrmatory RIBA. However, all conﬁrmed

anti-HCV test results should be followed by a test for the presence of HCV

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54 HEPATITIS AND LIVER CANCER

RNA (Alter et al., 2003; Ghany et al., 2009). The difﬁculty in identifying

chronic cases often revolves around the need for two separate tests (or

other supplemental antibody tests) and the 6-month timeframe required for

a diagnosis of chronic HCV infection. Many infected people are tested at

public or nonclinical testing sites—such as drug-treatment facilities, sites for

testing for HIV or STDs, or community-based organizations—that conduct

only the less expensive anti-HCV tests. Persons tested at those sites might

not have access to an HCV RNA test, or the laboratory conducting the

initial EIA test might not routinely test for HCV RNA when an EIA has

been positive. The process leads to incomplete diagnoses and inaccurate

reporting of the number of chronic cases.

The CDC-recommended case deﬁnition of nonacute HCV infection

also poses some problems in interpreting the collected data. Although it is

assumed that the majority of nonacute hepatitis C cases represent chronic

infections, this case deﬁnition also includes acute cases that do not meet the

conﬁrmed acute case classiﬁcation (CDC, 2005a). However, a case deﬁned

only by the presence of anti-HCV could be a late acute infection, a chronic

infection, a resolved infection, or a false-positive assay result. It is therefore

essential that anti-HCV testing be supplemented by testing for HCV RNA

and by followup samples to classify cases correctly and to use the data for

program-planning purposes.

Identifying Perinatal Hepatitis B

Since 1992, CDC has awarded funds to 64 grantees to support peri-

natal hepatitis B prevention programs through its Immunization Services

Division’s cooperative agreements with health departments. The funds sup-

port perinatal hepatitis B coordinators, who are charged with identifying all

HBsAg-positive pregnant women, ensuring the administration of appropri-

ate immunoprophylaxis to all infants born to these women, ensuring the

completion of postvaccination serologic testing of the infants, and ensuring

the completion of the hepatitis B vaccine series. Most coordinator programs

also include ensuring vaccination of household contacts and sexual partners

of HBsAg-positive women in their mission (CDC, 2009g).

In an economic analysis of immunization strategies to prevent hepatitis

B transmission in the United States, Margolis et al. (1995) found that pre-

vention of perinatal infection and routine infant vaccination would reduce

the lifetime risk of HBV infection by at least 68%. They estimated that

prevention of perinatal HBV infections would save $41.8 million in medi-

cal and work-loss costs. Routine hepatitis B vaccination of infants would

provide additional savings of $19.7 million. Both strategies were found to

be cost-effective, with estimated costs per year of life saved of $164 for

preventing perinatal HBV infection and of $1,522 for infant vaccination.

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In 1992, the Connecticut Department of Public Health found that

hiring a state-level perinatal coordinator led to signiﬁcantly better compli-

ance with the recommendation to administer hepatitis B immune globulin

(HBIG) than followup by local health departments. They also found that

completion of the three-dose vaccination series was higher in cases followed

by the state coordinator than in those followed by local public-health of-

ﬁcials (CDC, 1996).

Two major problems occur in the identiﬁcation and management of

possible cases (see Box 2-6). The ﬁrst involves linking pregnancy status

with positive HBsAg laboratory reports on females of child-bearing age in

a timely manner. In 2005, the Advisory Committee on Immunization Prac-

tices called for improving prevention of perinatal and early childhood HBV

transmission by improving laws and regulations to improve identiﬁcation

of HBsAg-positive and HBsAg-undetermined mothers (Mast et al., 2005).

BOX 2-6

CDC Perinatal Hepatitis B Virus Infection Case Definition

Clinical description

Perinatal hepatitis B in the newborn may range from asymptomatic to

fulminant hepatitis.

Laboratory criteria

HBsAg positive

Case classiﬁcation

HBsAg positivity in any infant aged >1–24 months who was born in the

United States or in US territories to an HBsAg-positive mother

Comment: Infants born to HBsAg-positive mothers should receive hepa-

titis B immune globulin (HBIG) and the ﬁrst dose of hepatitis B vaccine

within 12 hours of birth, followed by the second and third doses of vac-

cine at 1 and 6 months of age, respectively. Postvaccination testing for

HBsAg and anti-HBs (antibody to HBsAg) is recommended from 3 to 6

months following completion of the vaccine series. If HBIG and the initial

dose of vaccine are delayed for >1 month after birth, testing for HBsAg

may determine if the infant is already infected.

Abbreviations: CDC, Centers for Disease Control and Prevention; HBsAg, hepatitis B surface

antigen; anti-HBs, antibody to HBsAg; HBIG, hepatitis B immune globulin.

SOURCE: CDC, 2009a.

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56 HEPATITIS AND LIVER CANCER

Implementation of automated electronic systems can greatly increase the

speed with which cases can be identiﬁed (LaPorte et al., 2008), but they

are not available in most states. The second problem involves a lack of

resources to follow up on all potential and known cases and their contacts

in a timely manner. Followup of an infant can take up to 2 years. In addi-

tion, a substantial number of HBsAg-positive mothers are not identiﬁed in

time to ensure the required followup of the mothers and their infants (see

Chapter 4).

Other Challenges for Hepatitis B and Hepatitis C Surveillance Systems

Repeat testing in high-risk populations can confuse the number of sus-

pected acute versus chronic infections. Members of some populations, such

as IDUs, may repeatedly incur HCV infection that resolves spontaneously

without ever becoming chronic (Mehta et al., 2002). Those cases could mis-

takenly be classiﬁed as chronic infections based on antibody results alone.

Many of the people affected by hepatitis B and hepatitis C have limited

access to health care (for example, active IDUs, homeless people, some

Paciﬁc Islanders, legal immigrants living in poverty, and undocumented

immigrants) and are less likely to be diagnosed appropriately, to provide

complete and accurate demographic and behavioral information, or to

access followup care. Structural and political barriers, stigma, and fear

of legal repercussions contribute to the limitations on their access. Each

HBV-infected or HCV-infected person who does not enter into appropriate

medical care represents a missed opportunity for secondary prevention and

may contribute to the collection of inaccurate and less detailed surveillance

data. Finding ways to ensure that patients receive comprehensive and cul-

turally appropriate care and referrals not only would increase the likelihood

of improving their health outcomes but is likely to affect surveillance-data

collection favorably.

Finally, because of the chronic nature of viral hepatitis, it is important

that surveillance staff communicate well between jurisdictions. Persons

with chronic disease can be misclassiﬁed as having acute cases if earlier

diagnoses made in other jurisdictions are not identiﬁed. Not infrequently,

a previous diagnosis has been reported in another state or jurisdiction. The

ability of state and local surveillance-program staff to track cases across

jurisdictions is hampered by various factors, including inadequacy of staff

resources, nonstandardized surveillance software systems, and the lack of a

national database that could be used to identify potential matches in other

jurisdictions.

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INFRASTRUCTURE AND PROCESS-SPECIFIC

ISSUES WITH SURVEILLANCE

Current public-health surveillance systems for hepatitis B and hepati-

tis C are poorly developed and are inconsistent among jurisdictions. As a

result, surveillance data do not provide accurate estimates of the current

burden of disease, are insufﬁcient for program planning and evaluation,

and do not provide the information that would allow policy-makers to al-

locate sufﬁcient resources to address the problem. The AVHPCs, funded by

CDC in state and territorial health departments, are tasked with identifying

mechanisms for educating the public, at-risk populations, and medical-

service and social-service providers about viral hepatitis; for managing and

coordinating viral-hepatitis prevention activities; and for integrating viral-

hepatitis screening programs and related services into health-care settings

and public-health programs that serve at-risk adults. In most cases, how-

ever, CDC funding covers only the AVHPC’s salary. No funding is provided

for viral-hepatitis testing, hepatitis B immunizations, or other services.

Most important, AVHPCs are not funded to conduct surveillance activities,

although many of them provide technical assistance for such programs.

In addition, CDC’s DVH has scant resources for providing funding and

guidance to local and state health departments to perform surveillance for

viral hepatitis. The resources provided for viral-hepatitis surveillance con-

trast sharply with the resources that CDC provides for HIV surveillance.

For example, CDC has speciﬁc cooperative agreements with the states and

territories to conduct core HIV/AIDS surveillance activities. The coopera-

tive agreements are accompanied by dedicated funding, speciﬁc CDC proj-

ect ofﬁcers and epidemiologists, regular technical-assistance meetings and

training, and a help desk that has trained staff to answer database-related

questions. The guidance for HIV/AIDS surveillance is a three-volume set

containing more than 500 pages of detailed instructions, standards, and

guidelines. In contrast, CDC’s cooperative agreements with state and ter-

ritorial health departments for viral hepatitis do not include surveillance

activities. In addition, although CDC’s DVH has produced guidelines for

viral-hepatitis surveillance for state and territorial health departments, they

are presented in fewer than 50 pages (CDC, 2005a). Given that the guide-

lines cover three distinct and complex diseases (hepatitis A, hepatitis B, and

hepatitis C), they lack the detail necessary to create surveillance practices

that are consistent among jurisdictions. As a result of the deﬁciency of

resources dedicated to hepatitis surveillance, data are incomplete, variable,

and inaccurate. Inconsistency between jurisdictions seriously undermines

the validity of the data provided at the state, regional, and national levels.

The inability of health departments to track all diagnosed cases also se-

riously undermines case-management and prevention efforts. For example,

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58 HEPATITIS AND LIVER CANCER

studies have shown that vaccinating close contacts of persons chronically

infected with HBV (that is, ring vaccination) is cost-effective (Hutton et al.,

2007). The strategy remains cost-effective even in populations in which the

prevalence of chronic HBV infection is as low as 2%. However, without

funding and stafﬁng for surveillance and identiﬁcation of new cases of HBV,

ring vaccination is not a public-health activity that is typically supported

by most health departments.

CDC has funded seven enhanced projects through the Viral Hepatitis

Surveillance Emerging Infections Programs (EIPs). The projects began in

2004 and were scheduled to end in 2009. CDC plans to extend the pro-

gram for 2 more years (personal communication, J. Eﬁrd, CDC, May 18,

2009). They are in Colorado, Connecticut, Minnesota, New York state,

New York City, Oregon, and San Francisco. Although the projects focus on

surveillance for hepatitis A, hepatitis B, and hepatitis C, they all take differ-

ent approaches, including multiple approaches in individual jurisdictions.

Project funding supports epidemiologic and data-entry stafﬁng. Methods

used in the seven programs include veriﬁcation of diagnoses with medical

providers, chart review, followup calls to infected persons that focus on

education or data collection, educational mailings (for example, letters

and booklets), followup with persons that are household or close contacts

(especially acute HBV cases), sampling for followup of cases of chronic

HBV and HCV, review of all data, and matching with HIV and STD pro-

grams. There is no uniform evaluation of the projects.

In February and March 2009, staff of the National Alliance of State

and Territorial AIDS Directors (NASTAD) interviewed the coordinators of

the seven EIPs. From those interviews, staff identiﬁed additional program-

matic issues that affect reporting. They include resource issues, such as

the varied capacity of county and city health departments (which leads to

inconsistencies in data collection and data systems, in some instances in the

same state); the stafﬁng requirements needed to collect, process, and man-

age data; and the staff and time needed to investigate health-care–related

outbreaks adequately. Other issues are the need to educate medical provid-

ers better on which laboratory tests are needed for appropriate diagnosis

(also noted by Fleming et al., [2006]), and the difﬁculty that staff face in

obtaining demographic data (including data on race, ethnicity, and country

of origin) and data on risk history (Klevens et al., 2009; NASTAD, 2009).

Funding Sources

Funding for hepatitis surveillance is highly fragmented. No federal

funds are dedicated to chronic-hepatitis surveillance except for the seven

jurisdictions that receive funds from CDC’s DVH to perform enhanced

surveillance activities. State, territorial, or city health-department viral-

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hepatitis surveillance units, where they exist, often receive no dedicated fed-

eral funding for this activity. Others may receive funding directly from their

state or city, or they may be integrated into or receive funding from other

programs or units that receive federal funding from CDC programs whose

missions are related to epidemiology or viral hepatitis. The CDC programs

include the Immunization Services Division (related to perinatal hepatitis

B), the Epidemiology and Laboratory Capacity for Infectious Diseases pro-

gram (acute hepatitis B), EIPs, and the DVH. Funding may also be avail-

able through private organizations or foundations. Some surveillance units

receive funding from multiple sources. Each funding source may require

different activities and may provide varied guidance on the receiving unit’s

activities. The recent survey of AVHPCs conducted by NASTAD found that

fewer than one-fourth of the 43 responding jurisdictions reported receiving

funding for surveillance for either chronic HBV or chronic HCV infection

(NASTAD, 2009).

Program Design

Variability among jurisdictions is also due to a wide array of program

structures. In a 2006 survey, 33% of the 52 hepatitis C coordinators funded

by CDC reported being in their jurisdictions’ communicable-diseases or epi-

demiology programs, 25% in HIV–STD programs, 14% in HIV programs,

and the remainder in the immunization or STD programs (CDC, 2006). The

hepatitis C coordinators’ locations within public health departments may

or may not correspond with the health department program responsible

for conducting surveillance, which can lead to reduced involvement and

oversight by the coordinator of viral hepatitis surveillance activities.

In a later survey of the (renamed) AVHPCs by CDC in April 2009,

only 32 states reported having state viral-hepatitis plans. Of the 32, 29

included surveillance as a component. However, fewer than two-thirds of

the program coordinators reported being able to implement the surveillance

components. The reasons listed for not implementing plan components

were lack of staff and lack of funding (CDC, 2009h).

Reporting Systems and Requirements

Reporting of surveillance data to CDC by state and territorial health

departments is voluntary, and in general little federal funding is provided

for HBV and HCV surveillance activities (Klein et al., 2008). Chronic

hepatitis B is reportable in 42 states, but only 38 states conduct surveil-

lance and maintain systems, and only 20 report cases to CDC (George,

2004). Chronic hepatitis C is reportable in 40 states, but only 20 report

cases to CDC (George, 2004). CDC collects data from states that report

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60 HEPATITIS AND LIVER CANCER

chronic HBV and HCV infections (and received data on 133,520 cases of

HCV infection in 2007 alone), but these data are not presented routinely

in Morbidity and Mortality Weekly Report, which is published by CDC, or

elsewhere (Klevens et al., 2009). Although all states but one perform some

degree of surveillance for acute HBV and HCV (Daniels et al., 2009b),

much of this surveillance is passive at best.

There are signiﬁcant barriers to implementing more comprehensive

surveillance activities. In the previously mentioned survey conducted by

NASTAD in 2009, it was reported that of the 43 responding jurisdictions,

almost half received between 1,000 and 10,000 HBV laboratory results

annually, and over 70% reported the same range for the number of HCV

laboratory results received annually (NASTAD, 2009). Many states do not

have the stafﬁng or systems to keep up with such a high volume of informa-

tion received and are often unable to follow up with medical providers to

address underreporting or to obtain demographic and risk-history informa-

tion, such as race, ethnicity, and drug-use details (Klein et al., 2008). The

lack of funding to hire adequate staff is the fundamental barrier to complete

and accurate surveillance.

Although CDC provides case-reporting forms for the collection of

viral-hepatitis surveillance data, the forms do not have required elements,

and they ask for data that are often difﬁcult to obtain. Moreover, the use

of the forms is inconsistent among states and local jurisdictions. Of the 43

health departments that responded to inquiries from the present commit-

tee, 26 have developed their own HBV case-reporting form, and 21 have

developed an HCV case-reporting form. The forms were created to capture

behavioral-risk information not included on CDC’s form or to improve

data collection and entry into the separate jurisdictions’ speciﬁc software

systems. For example, the CDC case-reporting form does not collect risk-

behavior information speciﬁc to chronic HBV. Finally, 8 states do not use a

case-reporting form at all for reporting HBV, and 12 states do not use one

for HCV; these jurisdictions rely solely on the reporting of laboratory-test

results.

Paradoxically, efforts to modernize and enhance public-health surveil-

lance systems have led to greater inconsistency in data collection. In 1984,

CDC began work on the Epidemiologic Surveillance Project. The goal of

the project was to develop computer-based transmission of public-health

surveillance data between states and CDC. By 1989, all 50 states were

participating in the reporting system for certain acute infectious diseases,

and the system was renamed the National Electronic Telecommunications

System for Surveillance (NETSS) (CDC, 2009f). Data were transmitted

weekly to CDC in a standard record format. However, the system quickly

became dated with advances in information and surveillance technology,

such as electronic laboratory reporting and electronic medical records.

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Moreover, other surveillance systems and software were used for reporting

of HIV/AIDS, STDs, tuberculosis, and some vaccine-preventable diseases.

In 1999, CDC developed the concept of the National Electronic Disease

Surveillance System (NEDSS), which was designed to promote the develop-

ment of interoperable surveillance systems (that is, the Public Health Infor-

mation Network, or PHIN) at federal, state, and local levels (CDC, 2009e).

The NEDSS initiative describes information-system standards to which all

systems must adhere but does not require use of CDC-produced software.

CDC provides the NEDSS Base System, a software system that may be used,

but only 16 jurisdictions have opted to use it. Most jurisdictions use PHIN-

compliant systems, which are either purchased from a commercial vendor

or developed speciﬁcally for a particular jurisdiction. A few jurisdictions

continue to use the NETSS system while their PHIN-compliant systems are

being developed (personal communication, J. Eﬁrd, CDC, April 1, 2009).

The result is that CDC no longer provides a standardized database for in-

putting and reporting data on viral hepatitis. Consequently, there is a wide

array of state systems with an even wider array of capabilities. The lack of

standardization makes it difﬁcult for states to share information efﬁciently.

In addition, creating and modifying their systems can lead to substantial

expenses for states and jurisdictions (CDC, 2009i).

Even states and jurisdictions that have PHIN-compliant systems in

place may not have the staff to enter the high volume of viral-hepatitis data

received. Four of the 43 states that responded to the recent questionnaire

for this committee reported not having any staff to enter data. They do

not include states that may not be able to enter all received data fully. In

the 2009 NASTAD survey of AVHPCs, it was reported that 27 of the 43

reporting jurisdictions had backlogs of HCV data, with an average of 6,200

cases that needed to have data entered (NASTAD, 2009).

Capturing Data on At-Risk Populations

As discussed previously, current surveillance systems do not adequately

capture cases of acute and chronic HBV and HCV infections. That is par-

ticularly true for members of marginalized populations. IDUs are at high

risk for both HBV and HCV infections. The incidence of HCV infection

in IDUs ranges from 2% to 40% per year, with most rates in the range of

15–30% per year

(Maher et al., 2006; Mathei et al., 2005; van den Berg et

al., 2007), and the incidence of HBV infection from 10% to 12% per year

(Ruan et al., 2007). A study of IDUs in Seattle looked at those who became

infected with HBV or HCV during the 12-month study period. The study

matched study participants who had become infected to those identiﬁed in

HCV prevalence is calculated in percentages from person years.

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62 HEPATITIS AND LIVER CANCER

the health department’s surveillance database. Of the 113 study participants

who became infected, only two cases of those identiﬁed in the study were

picked up by the state’s surveillance system (Hagan et al., 2002). None of

the 65 acute HCV infections in IDUs was reported.

Enhanced sero-surveillance studies, such as the National Health and

Nutrition Examination Survey (NHANES), which are often used to provide

supplemental data and prevalence estimates when surveillance systems are

inadequate or incomplete, have serious limitations when addressing viral

hepatitis. For example, NHANES, the study most commonly used to es-

timate the disease burden of chronic HBV and HCV infections, excludes

or underrepresents populations that are most at risk for HBV and HCV

infections. Those populations include homeless persons, institutionalized

and incarcerated persons, and persons of Asian and Paciﬁc Island descent.

About 1.5 million people are in state or federal prisons in the United States

(Department of Justice, 2009). CDC estimated chronic HBV prevalence

in the adult prison population to be around 1–3.7%, and the prevalence

of chronic HCV infection has been reported to vary from 12–35% (CDC,

2003c). Thus, the national estimate of 2.7–3.9 million people chronically

infected with HCV (CDC, 2009b; Daniels et al., 2009a) potentially excludes

several hundred thousand cases. Similarly, Asians, Paciﬁc Islanders, Ameri-

can Indian, and Alaska Native people are undersampled among NHANES

participants (Coleman et al., 1998). Given the higher prevalence of HBV

in those populations, NHANES underreports the number of chronic HBV

cases in the national estimates (Kim, 2007).

A supplemental HIV surveillance project funded by CDC’s Division of

HIV/AIDS Prevention is the National HIV Behavioral Surveillance System.

The system surveys persons at high risk for HIV infection in cities with high

rates of AIDS diagnoses to determine their risk behavior, testing behavior,

and use of prevention services. Even though IDUs are one of the targeted

populations studied through the system (CDC, 2009d), HCV testing has

not been included systematically as part of the study design, and this leads

to missed opportunities to deﬁne the injection and injection-related behav-

iors as they apply to HCV and HCV prevention.

Case Evaluation, Followup, and Partner Services

The reporting of a case of hepatitis B or hepatitis C by a public test site

or private clinic provides an opportunity for public-health followup. Part of

the followup generally involves ensuring that the persons with the reported

diagnoses and their partners receive proper medical evaluation, counseling,

vaccination, and referrals to support services as needed (Fleming et al.,

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2006). An inability of a health department to identify a case becomes a

missed opportunity to prevent future cases and to ensure that HBV-infected

and HCV-infected people receive the care that they need.

In 2007, the Massachusetts Department of Public Health piloted the

use of STD disease intervention specialists (DISs) to follow up on cases

of HCV infection in people 15–25 years old. The DISs were tasked with

collecting risk-history data and providing partner-notiﬁcation services for

drug-sharing partners of the infected people. There was some success in

reaching a small sample of the high volume of infected people, but no

funding was available to support the staff. In addition, the DISs had com-

peting priorities that kept the department from being able to implement

its methods fully so that they could be appropriately evaluated (Onofrey

et al., 2008).

Given the demands on staff, most state health-department surveillance

units indicated that they were barely able to keep up with the basics of

data collection. The 2009 NASTAD survey found that only 18 of the 43

jurisdictions conducted any type of followup; in the ones that did conduct

followup, there was wide variation in what that comprised (NASTAD,

2009). Followup can consist of making calls to providers or cases to collect

demographic, clinical, or risk-history data and contacting infected people

by mail, by telephone, or in person to provide education or referral to medi-

cal services. For the most part, even the best resourced surveillance units are

able to conduct only very limited case management (Fleming et al., 2006).

Furthermore, the utility and cost effectiveness of conducting partner

services for persons who test positive for HBV or HCV is yet to be deter-

mined. Currently, states conduct partner notiﬁcation for HIV and some

STDs. Services include notifying sex or needle-sharing partners of exposure

to disease and testing, counseling, and referrals for other services. Newly

revised CDC guidelines on partner services strongly recommend partner

services for persons reported to have HIV or early syphilis; services for

gonorrhea and chlamydial infection are recommended for high-priority

cases as resources allow (CDC, 2008e). Recommendations for persons

who have viral hepatitis were not included in the HIV and STD integrated

guidelines.

Recommendations

Recommendation 2-1. The Centers for Disease Control and Prevention

should conduct a comprehensive evaluation of the national hepatitis B

and hepatitis C public-health surveillance system.

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64 HEPATITIS AND LIVER CANCER

The evaluation should, at a minimum,

• Include assessment of the system’s attributes, including complete-

ness, data quality and accuracy, timeliness, sensitivity, speciﬁcity,

predictive value positive, representativeness, and stability.

• Be consistent with CDC’s Updated Guidelines for Evaluating Public

Health Surveillance Systems.

• Be used to guide the development of detailed technical guidance

and standards for viral hepatitis surveillance.

• Be published in a report.

The committee found little published information on or systematic

review of viral-hepatitis surveillance in the United States. Speciﬁc informa-

tion was obtained from a series of surveys of the AVHPCs. In contrast,

the history and status of national HIV surveillance is well reviewed and

documented (CDC, 1999; Glynn et al., 2007; Nakashima and Fleming,

2003).

In July 2001, CDC published updated guidelines for evaluating public-

health surveillance systems (CDC, 2001b). According to the guidelines,

the evaluation should “involve an assessment of system attributes, includ-

ing simplicity, ﬂexibility, data quality, acceptability, sensitivity, predictive

value positive, representativeness, timeliness, and stability.” The lack of

sensitivity of state hepatitis-surveillance systems is well documented for

acute cases, and many states do not perform surveillance for chronic HBV

or chronic HCV infections. Moreover, the movement of CDC away from

NETSS, a CDC-provided system, and toward a national network of PHIN-

compliant systems has left state and territorial health departments with a

wide array of software systems and capabilities (CDC, 2009i). A compre-

hensive review is needed to document the current systems and capacities

of public-health jurisdictions. The evaluation should focus on developing

guidance to improve consistency of data, guide the development of detailed

technical guidance and standards for hepatitis-surveillance programs, and

allow CDC to improve understanding and description of the limitations of

the data collected. Completion of this task should not delay the implemen-

tation of other components of the surveillance-related recommendations

in this report.

Recommendation 2-2. The Centers for Disease Control and Prevention

should develop speciﬁc cooperative viral-hepatitis agreements with all

state and territorial health departments to support core surveillance for

acute and chronic hepatitis B and hepatitis C.

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The agreements should include

• A funding mechanism and guidance for core surveillance activities.

• Implementation of performance standards regarding revised and

standardized case deﬁnitions, speciﬁcally through the use of

 o Revised case-reporting forms with required, standardized

components.

 o Case evaluation and followup.

• Support for developing and implementing automated data-collection

systems, including

 o Electronic laboratory reporting.

 o Electronic medical-record extraction systems.

 o Web-based, PHIN-compliant reporting systems.

CDC should provide more comprehensive guidance to states on sur-

veillance for viral hepatitis. The committee suggests that CDC use the HIV

surveillance system as a model. The committee focused on that surveillance

model as an alternative to the current model because of its organization,

availability of technical assistance, and provision of detailed guidelines. The

strength of the model is in its centralized guidance, mandatory process and

outcome standards, and oversight at a national level, all of which provide

consistency in data among jurisdictions (Hall and Mokotoff, 2007).

CDC is able to oversee its national effort through separate cooperative

agreements with each state and territory for speciﬁc core HIV surveillance

activities (CDC, 2007). The agreements not only provide funding for enough

dedicated staff to provide followup directly with providers and to conduct

active surveillance but commit states and territories to speciﬁc methods and

performance expectations. States are also provided with detailed guidance

on case investigation, classiﬁcation, and followup requirements (CDC/

CSTE, 2006). To ensure consistency, CDC holds required disease-speciﬁc

technical-assistance meetings for all grantees. Project ofﬁcers and epide-

miologists are assigned to each grantee. As of April 2008, all states and

territories had implemented the conﬁdential, name-based reporting method

used for all other reportable infectious diseases (CDC, 2008d). The national

HIV surveillance system will soon be able to achieve case counts with no

duplicates among jurisdictions through an interstate reciprocal notiﬁcation

system wherein CDC provides quarterly reports on cases that might be

duplicated between states on the basis of matching soundex codes,

dates

A soundex code is a coded last name index based on the way a surname sounds rather

than the way it is spelled. It is a census coding system developed so you can ﬁnd a surname

even if it may have been recorded under various spellings. A soundex code consists of a letter

and three numbers (CDC/CSTE, 2006).

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66 HEPATITIS AND LIVER CANCER

of birth, race, and sex. There is also guidance and sufﬁcient stafﬁng to be

able to investigate cases of public-health importance, including clusters of

unusual clinical, laboratory, or geographic occurrences; cases with unusual

modes of transmission; cases without detectable antibody response; and

cases with unusual strains of HIV, such as HIV-2 and non-B subtypes.

Another aspect of the HIV surveillance model is that all jurisdictions

use standardized HIV/AIDS case-report forms. Speciﬁc information must

be completed before the software system will classify an entry as a case;

this information includes laboratory or provider diagnosis conﬁrmation,

and patient’s date of birth, race, ethnicity, and sex. The case-report form

includes the collection of behavioral-risk information, measures of immu-

nologic function (CD4+ cell count and percentage), and viral load.

Most important, the HIV model includes process and outcome stan-

dards that all jurisdictions must strive to achieve (CDC, 1999). The outcome

standards include completeness, timeliness, accuracy, risk ascertainment,

and collection of ﬁrst CD4+ cell count. Because the new software system is

document-based, it will enable evaluation of the completeness of national

case ascertainment with a capture-recapture method (Hall et al., 2006). The

resulting information can be used to determine weaknesses in the reporting

system and to help interpret data appropriately.

Finally, the process and outcome standards have been incorporated into

CDC’s updated framework for evaluating public-health surveillance sys-

tems (Hall and Mokotoff, 2007). CDC assesses national HIV surveillance

data against the required outcome standards annually. The HIV/AIDS sur-

veillance evaluation framework promotes continuous improvement in the

quality of data through technical guidance, measurement of performance,

reporting of assessment results to state and local health departments, and

adjustments in guidance, training, or technical assistance according to as-

sessment results.

The cooperative agreement and the associated funding have allowed the

development of the national HIV surveillance system. Both are imperative

for the development of an accurate, timely, and complete hepatitis surveil-

lance system that will provide accurate incidence and prevalence data to

inform proper resource allocation, program development and evaluation,

and policy-making.

The following section details the committee’s recommended model for

structuring surveillance for hepatitis B and hepatitis C.

MODEL FOR SURVEILLANCE

The committee recommends that a two-tiered model be developed:

core surveillance and targeted surveillance. The initial focus of the program

should be the development and implementation of standardized systems

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among all states to maximize their capacity to perform core surveillance for

acute and chronic HBV and HCV infection. Standardization will be accom-

plished through cooperative agreements, improved guidance, and adequate

and consistent funding. Systems should be integrated into existing HIV or

other disease surveillance infrastructure where feasible. Complementary

efforts need to be made in building enhanced supplemental surveillance

systems to describe trends in underrepresented at-risk populations better

and to address the gaps identiﬁed in the current surveillance system. Both

types of surveillance activities will provide better information to policy-

makers and service-delivery systems to improve care for people who are at

risk for or living with HBV or HCV infection. Changes should be phased

and prioritized, with the ﬁrst step focused on the development and funding

of core surveillance systems for each state.

Core Surveillance

Core surveillance—including collection, processing, analysis, and

dissemination of data on cases of acute and chronic HBV and HCV

infection—is needed in all states. Because of the public-health importance

of quick identiﬁcation of outbreaks and nosocomial transmission, acute-

disease surveillance has had the highest priority in surveillance programs

in the past. However, chronic-disease surveillance is also critical in that, if

funded appropriately, it will assist in the recognition of acute cases, aid in

moving people with recent diagnoses into appropriate care, contribute to an

increased understanding of disease burden, allow evaluation of prevention

efforts, and, given appropriate case management, save on costs associated

with treatment of patients who have cirrhosis, hepatocellular carcinoma, or

liver transplantation. Proper chronic-disease surveillance can also improve

acute-disease surveillance by enhancing the accuracy and efﬁciency of re-

lated data collection. Evaluation of the core surveillance system should be

ongoing to ensure that it is meeting emerging needs.

Funding Mechanism

In the proposed model, the state would be the primary unit of surveil-

lance. Funding should be earmarked for viral-hepatitis surveillance through

cooperative agreements with the states. CDC should ensure that all states

have sufﬁcient infrastructure to identify and appropriately investigate all

suspected cases of acute and chronic HBV and HCV infection. Cooperative

agreements should require reporting of standardized viral-hepatitis sur-

veillance data within 3 years of implementation. The agreements should

include funding for states to hire staff to process laboratory results, enter

data, and follow up cases of acute and chronic HBV and HCV infections.

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68 HEPATITIS AND LIVER CANCER

Case Deﬁnitions

CDC should revise and standardize deﬁnitions and methods. Revised

case deﬁnitions should reﬂect active and resolved hepatitis C infection (for

example, a case should not be conﬁrmed if only antibody test results are

available). Recommended testing for hepatitis C should include, where pos-

sible, HCV RNA tests to determine whether a person is actively infected.

The case deﬁnition for acute HBV and HCV infection should be revised

to remove the need for symptoms for classiﬁcation as a conﬁrmed case.

Classiﬁcation as a suspected case of acute HCV infection should be used

to encourage active followup of likely recent infections (for example, in

adolescents and young adults) (CDC, 2008f).

Case-Reporting Form

The case-reporting form should be standardized, and core components

of it should be required of all jurisdictions to permit better capture of

information on cases of acute and chronic HCV and HBV infection. The

required elements should be such that they could reasonably be found in a

patient’s medical record. For example, the current CDC form requests the

number of sexual partners in a given period. That information is not typi-

cally found in a medical record or known by a medical provider. Additional,

more comprehensive epidemiologic studies could be funded to provide for

patient interviews and a detailed assessment of risk factors (see Recom-

mendation 2-3). Furthermore, the case-reporting form should collect more

detailed demographic data on racial and ethnic populations to identify and

address disparities among populations. For example, the case-reporting

form should include categories for different ethnicities and should disag-

gregate Asians and Paciﬁc Islanders (for example, Chinese, Vietnamese,

Japanese, and Marshallese).

Automated Data-Collection Systems

Automated or passive methods of accessing and processing test results

should be supported and improved. Enhancing and expanding automated

methods of collecting data (for example, Web-based disease-reporting sys-

tems, electronic laboratory reporting, and electronic medical records) reduce

staff time, increase timeliness and completeness, and minimize data-entry

errors (Klevens et al., 2009; Klompas et al., 2008; Lazarus et al., 2001;

Panackal et al., 2002; Vogt et al., 2006; Wurtz and Cameron, 2005). Given

the volume of viral-hepatitis data, automated systems clearly are indicated

(Hopkins, 2005). However, it has been noted that although electronic

laboratory reporting can greatly increase the timeliness and accuracy of

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reporting, it does not remove the need for health departments to conduct

additional followup to obtain information not contained in laboratory

reports, such as symptoms, race and ethnicity, and risk history (Hopkins,

2005; Klevens et al., 2009).

A pilot study of a surveillance system based on electronic medical re-

cords in Massachusetts found a 39% increase in reported cases of chlamydia

and a 53% increase in reported cases of gonorrhea over a 12-month period

compared with cases reported through the existing passive surveillance

system. The system was also able to identify 81 instances of pregnancy not

identiﬁed by passive surveillance in patients with chlamydia or gonorrhea

(CDC, 2008b). The system was shown to identify cases of acute HBV in-

fection reliably, including cases that had not yet been reported to state au-

thorities (Klompas et al., 2008). Other studies have found a similar beneﬁt

of improving surveillance for infectious diseases via automatic notiﬁcation

with electronic medical records (Allen and Ferson, 2000; Hopkins, 2005).

CDC should promote the use of surveillance systems based on electronic

medical records and open-source platforms that will enable the extraction

and transmission of data to state and local health departments.

Standardized Laboratory Reporting It is essential that laboratory data be

standardized and that health departments have automated access to them.

Automated electronic laboratory reporting improves the completeness and

timeliness of disease surveillance (Efﬂer et al., 1999, 2002; Overhage et

al., 2008; Panackal et al., 2002; Ward et al., 2005). Currently, many

laboratory-data collection systems do not integrate or link the multiple

laboratory tests needed to satisfy a case deﬁnition (CDC, 2008b). That

could be more easily addressed with electronic laboratory reporting. CDC

should work with states and laboratories to develop and standardize elec-

tronic systems. In addition, it may be useful for CDC to document and

monitor which laboratory tests are reportable in each state, as is done for

the HIV surveillance system.

Identifying Pregnant Women There is a strong need to identify pregnant

women who have chronic HBV to ensure that appropriate followup of

the newborn is conducted with regard to receipt of HBIG and hepatitis B

vaccine. Currently, most health departments lack an automated means of

determining whether the subject of a reported positive HBsAg test was a

pregnant woman. Local health departments have to investigate all positive

hepatitis B tests in women of childbearing age, and this creates a substantial

workload. CDC should work with national laboratory vendors to identify

ways of reporting whether positive HBV tests are linked with prenatal pan-

els. Web-based surveillance systems may be useful for improving capture of

data on pregnant women who have HBV infection (LaPorte et al., 2008).

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70 HEPATITIS AND LIVER CANCER

PHIN-Compliant Systems CDC needs to contribute to more timely de-

velopment of PHIN-compliant systems in all jurisdictions. A review of the

literature evaluating the timeliness of reporting of infectious diseases found

that reporting lag and the variability among states limit the usefulness of

data. The inconsistency in reporting limits CDC’s ability to identify and

respond to multistate outbreaks in a timely manner. The review called for

a more standardized approach in evaluating and describing surveillance-

system timeliness (Jajosky and Groseclose, 2004). Although it did not look

speciﬁcally at hepatitis B or hepatitis C, its conclusions are relevant to the

present report.

Electronic Medical Records The reporting of relevant infectious-disease

test results should be a component of electronic medical-record systems.

CDC should support state and local jurisdictions in working with clinical

and community health-center partners to develop algorithms for auto-

matic viral-hepatitis disease reporting based on electronic medical records.

It has already been shown to be effective in enhancing acute-HBV report-

ing without adding to the burden on medical providers (Klompas et al.,

2008).

Case Investigation and Followup

Standards for case investigation and followup should be developed

and implemented to ensure that newly diagnosed patients receive ad-

equate information and referrals. An effective surveillance system should

identify most of the diagnosed cases of both acute and chronic HBV and

HCV infections. Identiﬁcation of infected people by health departments

should be the ﬁrst step in getting them into appropriate care. Because

of resource and system inadequacies, it is not. Most health departments

indicated that they were unable to do more than follow up on potentially

pregnant HBV-positive women (personal communication, Adult Viral

Hepatitis Prevention Coordinators, May 2009). If state health depart-

ments had appropriate funding to follow up recently diagnosed cases of

HBV and HCV infection directly, more people would be able to receive

appropriate education and referral into the array of medical and social-

service care that may be indicated.

Analyzing, Reporting, and Disseminating Findings

Once the capacity for state health departments to conduct HBV and

HCV surveillance is improved, CDC should report accurate results that are

based on the improved data. As discussed earlier in this chapter, there are

important concerns about underreporting, particularly of the incidence of

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acute HCV infection. Until the quality of the data collected has improved,

reports should clearly indicate the limitations of the data. For example,

• Trends in acute HBV and HCV infections should be interpreted

with caution because of systematically missing cases that represent

the burden of disease in particular risk groups.

• Discussions of data on acute HBV and HCV infections should

reﬂect the issue of the large number of chronic infections to ensure

appropriate understanding of the scope of the problem.

• Reported incidences should be presented as ranges rather than

single numbers to reﬂect the uncertainty of the estimates.

Targeted Surveillance

Once core hepatitis B and hepatitis C surveillance activities are well

established, supplemental or pilot projects should be tested. CDC should

develop and support innovative supplemental surveillance programs.

Recommendation 2-3. The Centers for Disease Control and Preven-

tion should support and conduct targeted active surveillance, including

serologic testing, to monitor incidence and prevalence of hepatitis B

virus and hepatitis C virus infections in populations not fully captured

by core surveillance.

• Active surveillance should be conducted in speciﬁc (sentinel) geo-

graphic regions and populations.

• Appropriate serology, molecular biology, and followup will allow for

distinction between acute and chronic hepatitis B and hepatitis C.

Enhanced Surveillance

Supplemental surveillance projects should be funded or conducted by

CDC and should include serosurveillance among targeted populations.

Serosurveillance projects will provide data for improved estimation of

the scope of the problem in underrepresented populations such as certain

racial and ethnic groups, and at-risk populations, including institutional-

ized, homeless, immigrant, and refugee populations. Enhanced surveillance

projects should be structured to obtain information in both rural and urban

regions of the United States. Serosurveillance programs should be ﬂexible

and allow researchers to focus on emerging behavioral risks, for example,

in adolescents and young adults and in HIV-positive men who have sex with

men (Klevens et al., 2009). Conducting serosurveillance or screening among

at-risk populations in correctional facilities may provide opportunities to

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72 HEPATITIS AND LIVER CANCER

collect more detailed data and to refer people directly into appropriate

medical care, including treatment for acute HCV infection (McGovern et

al., 2006). Other enhanced surveillance projects should include

• Determining the level of care that patients receive after diagno-

sis, including medical and social-service referrals and treatment

(Fleming et al., 2006).

• Following subsets of cases to improve understanding of natural

history (Global Burden of Hepatitis C Working Group, 2004).

• Matching data on chronic hepatitis B and hepatitis C with cancer

registries (Global Burden of Hepatitis C Working Group, 2004).

• Matching data on chronic HBV and HCV infections with HIV/AIDS

data to determine the burden of coinfection in communities.

• Measuring the vaccination status of acute HBV infection cases and

identifying missed opportunities for vaccination.

• Ensuring that viral hepatitis is addressed and integrated with ap-

propriate projects for the National HIV Behavioral Surveillance

System.

• Measuring HBV and HCV seroconversion rates in selected

populations.

Partner Services

Partner services have been found to be effective in identifying un-

diagnosed cases of HIV (Hogben et al., 2007). Similar programs could

potentially be useful identifying cases of hepatitis B and hepatitis C (CDC,

2008e; Hogben and Niccolai, 2009; Marcus et al., 2009). State and local

health departments should be funded to pilot and evaluate partner-services

programs for suspected acute and chronic cases of HBV infection and acute

cases of HCV infection, especially in young people. Integration with exist-

ing partner service programs should be explored. Evaluation should focus

on the efﬁcacy of referral into care services and on screening of exposed

partners—sexual partners for hepatitis B and drug-sharing partners for

hepatitis B and hepatitis C (CDC, 2007).

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Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C

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Knowledge and Awareness About

Chronic Hepatitis B and Hepatitis C

n estimated 0.8–1.4 million people in the United States are chroni-

cally infected with hepatitis B virus (HBV) and 2.7–3.9 million peo-

ple are chronically infected with hepatitis C virus (HCV). However,

there is relatively poor awareness about these infections among health-care

providers, social-service providers, and the general public. Lack of aware-

ness about the prevalence of chronic viral hepatitis in the United States and

about the proper methods and target populations for screening and medical

management of chronic hepatitis B and hepatitis C probably contributes to

continuing transmission; missing of opportunities for prevention, including

vaccination; missing of opportunities for early diagnosis and medical care;

and poor health outcomes in infected people.

As discussed in Chapters 1 and 2, surveillance data on the numbers of

people acutely and chronically infected with HBV and HCV are imprecise

and can be difﬁcult to interpret. The prevalence of chronic infections remains

high for several reasons, and the aging of the chronically infected population

has contributed to the tripling of liver-cancer incidence during the last three

decades (Altekruse et al., 2009; McGlynn et al., 2006). The persistently high

prevalence of chronic HBV infection can be attributed in part to immigra-

tion of chronically infected people from HBV-endemic regions—including

East Asia, Southeast Asia, and sub-Saharan Africa—to the United States.

The high prevalence of chronic HCV infection is due in part to the lack of

access to preventive measures, such as harm-reduction programs, and lack

of access to antiviral treatments in high-risk populations.

This chapter is divided into two sections. The ﬁrst addresses knowledge

and awareness about hepatitis B and hepatitis C in health-care providers

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80 HEPATITIS AND LIVER CANCER

and social-service providers; the second addresses the topic with reference

to the general population and at-risk populations. Each section begins by

describing what is known about the levels of knowledge and awareness

about hepatitis B and hepatitis C and how gaps in education about these

diseases are affecting prevention, screening and testing, and treatment op-

portunities. Those summaries are followed by the committee’s recommen-

dations for addressing the gaps and the rationale and supportive evidence

for the recommendations.

KNOWLEDGE AND AWARENESS AMONG

HEALTH-CARE AND SOCIAL-SERVICE PROVIDERS

The committee found that knowledge about chronic hepatitis B and

hepatitis C among health-care providers, particularly primary-care pro-

viders (for example, physicians, physician assistants, and nurse practitio-

ners), and social-service providers (for example, staff of drug-treatment

programs, needle-exchange programs, and immigrant services centers) is

generally poor. Although there have been no large-scale, controlled studies

of health-care providers’ knowledge about chronic hepatitis B and hepatitis

C, it is clear that knowledge has been imperfect among providers in all the

surveys whose results have been published. Subjects of deﬁcient knowledge

include

• The prevalence of chronic hepatitis B and hepatitis C in the general

and high-risk populations in the United States.

• The clinical sequelae of chronic viral hepatitis.

• The characteristics of at-risk persons who should be tested for

chronic HBV and HCV infection and vaccinated to protect them

from hepatitis B.

• The approaches to primary and secondary prevention in addition

to hepatitis B vaccination.

• The proper methods of testing and interpretation of test results.

• The proper followup management for chronic infection.

Provider guidelines for hepatitis screening, prevention, treatment, and

followup have been in place for decades and are updated regularly (CDC,

1991, 1998, 2005, 2008b, 2008c; Ghany et al., 2009; Lok and McMahon,

2009; Mast et al., 2005, 2006). However, current studies of provider

knowledge about chronic viral hepatitis have not identiﬁed why health-care

providers fail to follow national recommended guidelines.

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KNOWLEDGE AND AWARENESS ABOUT CHRONIC HEPATITIS B AND C 81

Hepatitis B

Studies have shown that many primary care providers cannot differenti-

ate between adult populations that should be screened for chronic hepatitis

B because of their high prevalence of chronic infection (for example, people

born in geographic regions with high HBV endemicity; see Box 3-1) and

populations that should be vaccinated against HBV because of their high

risk of becoming newly infected (for example, health-care workers, men

who have sex with men, prison inmates, and household and sexual contacts

of chronically infected individuals) (Euler et al., 2003b; Ferrante et al.,

2008; Lai et al., 2007).

In a survey of primary care providers in San Francisco, all 91 respon-

dents correctly answered that Chinese immigrants have a higher prevalence

of chronic hepatitis B than non-Hispanic white or US-born Chinese people.

However, a portion of the same group incorrectly identiﬁed HIV-infected

BOX 3-1

Geographic Regions That Have Intermediate and

High Hepatitis B Virus Endemicity

Africa: all countries

Asia and Middle East: all countries

South and Western Paciﬁc: all countries and territories but only indig-

enous persons in Australia and New Zealand

Eastern Europe: all countries except Hungary

Western Europe: Greece, Malta, Portugal, and Spain and indigenous

populations of Greenland

North America: Alaska natives and indigenous populations of northern

Canada

Central America: all countries

South America: Argentina, Bolivia, Brazil, Ecuador, Guyana, Suriname,

Venezuela, and Amazonian areas of Colombia and Peru

Caribbean: Antigua and Barbuda, Dominica, Dominican Republic, Gre-

nada, Haiti, Jamaica, Puerto Rico, St. Kitts and Nevis, St. Lucia, St. Vin-

cent and Grenadines, Trinidad and Tobago, and Turks and Caicos

SOURCE: Modiﬁed from Mast et al., 2006.

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82 HEPATITIS AND LIVER CANCER

persons (16%), men who have sex with men (18%), and injection-drug

users (IDUs; 23%) as having a higher prevalence of chronic hepatitis B

than Chinese immigrants (Lai et al., 2007). In the same study, 30% of the

respondents were not able to identify the correct test to use for diagnosing

chronic HBV infection.

A cross-sectional survey conducted among 217 members of the New

Jersey Academy of Family Physicians found that a higher proportion of

family physicians recommended screening for hepatitis B among men who

have sex with men (93%), IDUs (95%), and HIV-infected patients (96%)

than for immigrants from Southeast Asia (68%) or sub-Saharan Africa

(57%)—areas that are highly endemic for HBV with over 8% seropreva-

lence of hepatitis B surface antigen (HBsAg) (Ferrante et al., 2008). Only

50% of survey participants recommended screening household contacts of

persons who had chronic HBV infection—an established high-risk popula-

tion. Finally, 21% of the New Jersey family physicians did not know what

step to take next if a patient tested positive for HBsAg or would refer such

a patient to a specialist for followup (Ferrante et al., 2008). However, 83%

of the respondents were interested in receiving education about chronic

viral hepatitis.

Chu (2009) presented data at the 2009 International Symposium on

Viral Hepatitis and Liver Disease that showed that only 18–30% of Asian

American primary care providers who treat Asian American adult patients

reported routinely testing them for HBV infection in their practice. That

ﬁnding illustrates the incomplete knowledge even among primary care

providers who themselves constitute a group at high risk for chronic HBV

infection.

At the 2007 Society of General Internal Medicine annual meeting,

Dulay et al. (2007) reported on the results of a multiple-choice hepatitis

B knowledge survey completed by 196 attendees at a university-based

continuing-medical-education conference for primary care providers, in-

cluding nurse practitioners and physician assistants. Of the respondents,

55% were not able to identify HBsAg as the determinant for chronic HBV

infection. Knowledge about the appropriate use of the HBsAg test was sub-

stantially higher among primary care providers who were Asian (68%) than

those of other ethnicities (43%), among physicians (56%) than nonphysi-

cians (23%), and among providers who had more years of experience or

more time spent in the clinic. Some 44% of the respondents did not know

that chronic HBV infection could be controlled with medication, and 25%

incorrectly responded that chronic HBV infection is curable.

Given that the probability of developing chronic hepatitis B is highest

when infants are exposed to HBV through their mothers at birth, both the

US Preventive Services Task Force and the US Centers for Disease Control

and Prevention (CDC) recommend testing all pregnant women for HBsAg

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KNOWLEDGE AND AWARENESS ABOUT CHRONIC HEPATITIS B AND C 83

during an early prenatal visit even if they have been previously vaccinated

or tested (CDC, 1991; U.S. Preventive Services Task Force, 2009). Cur-

rently, only 27 states have maternal HBsAg screening laws (CDC, 2008c).

State screening laws do not necessarily translate into higher testing rates,

because they often do not include an enforcement mechanism or sanctions

for noncompliance (Euler et al., 2003b). In a study of family physicians in

New Jersey, a state with a maternal screening law, Ferrante et al. (2008)

found that 22% of respondents indicated that they did not recommend

testing pregnant women for HBV infection.

At the 2009 International Symposium on Viral Hepatitis and Liver

Disease, Chao et al. (2009b) presented results of a study of perinatal

health-care providers’ knowledge about hepatitis B and the management

of HBsAg-positive pregnant patients recommended by the Advisory Com-

mittee on Immunization Practices (ACIP). Questionnaires were mailed or

administered to 100 practicing obstetrician/gynecologists (OB/GYNs) and

31 peripartum nurses in Santa Clara County, CA, an area with one of the

largest annual numbers of HBsAg-positive pregnant women in the United

States. Although most of the OB/GYNs reported that they tested pregnant

women for HBsAg and properly advised HBsAg-positive women that their

newborns should receive the hepatitis B vaccine and hepatitis B immuno-

globulin within 12 hours of birth, overall knowledge about hepatitis B was

low. Only 26% of OB/GYNs and 10% of peripartum nurses knew that the

prevalence of chronic hepatitis B is higher in Asians than in other ethnic

populations; only 33% of OB/GYNs and 17% of peripartum nurses knew

that there is a high risk of HBV infection becoming chronic in exposed

newborns; and only 22% of OB/GYNs and 37% of peripartum nurses

knew about the risk of death conferred by chronic hepatitis B. Only 62% of

the OB/GYNs referred their HBsAg-positive pregnant patients for chronic-

hepatitis management.

Hepatitis C

Health-care providers’ knowledge about hepatitis C appears to be

similarly insufﬁcient, although there is far less published research on this

topic (Ascione et al., 2007; Ferrante et al., 2008; Shehab et al., 1999, 2001;

Strauss et al., 2006).

In the study of New Jersey family physicians described above, Ferrante

et al. (2008) found that although 95% would recommend testing of IDUs

for HCV infection, only 81% would recommend HCV testing for people

who received blood transfusions before 1992, and only 65% would recom-

mend testing of incarcerated persons—all populations that are at high risk

for HCV infection and that fall within national testing guidelines. Although

HCV testing of pregnant women is not supported by any evidence-based

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84 HEPATITIS AND LIVER CANCER

recommendations or guidelines, 34% of family physicians surveyed by

Ferrante et al. would nevertheless recommend it. Of the respondents, 31%

did not know what to do next or would refer a patient to a specialist after

a positive test for HCV antibody, and 2% incorrectly assured patients that

those who tested positive were immune to HCV. Physicians in practice

for more than 20 years were found to have the lowest level of knowledge

about HCV risk factors, whereas those in practice for 5 years or less had

the highest knowledge level.

A survey of 593 fellows of the American College of Obstetricians and

Gynecologists (ACOG), half of whom considered themselves to be primary

care providers, assessed screening and counseling practices for HCV infec-

tion. About half (49%) reported that they tested for HCV infection in all

obstetric and gynecologic patients who self-reported ever having injected il-

licit drugs, and 35% tested all patients who reported having received blood

transfusions before 1992 (Boaz et al., 2003). Nearly half counseled HCV-

infected patients to avoid breastfeeding, and 70% counseled HCV-infected

patients to use condoms with their steady sexual partners; both kinds of

advice are inconsistent with recommendations of CDC (CDC, 1998) and

ACOG (2000, as cited in Boaz et al., 2003). Only 64% recommended that

patients who had HCV infection avoid alcohol, which has been found to

increase the risk of disease progression (Ascione et al., 2007).

An earlier mailed survey of 1,412 primary care providers in the United

States also assessed knowledge about risk factors for HCV infection and

management of hepatitis C (Shehab et al., 2001). Nearly three-fourths

(73%) of the respondents had seen fewer than ﬁve hepatitis C patients

within the preceding year, and almost half (44%) had no experience with

treatment for HCV infection. Almost all knew the most common risk fac-

tors for HCV infection—injection-drug use, blood transfusion during the

1980s, and multiple sex partners. One-fourth incorrectly indicated that

blood transfusion continues to be a risk factor, and 19% erroneously be-

lieved that casual household contact is a major risk factor. Some 50% of the

providers reported that they routinely ask their patients about risk factors

for HCV infection; 78% test for HCV infection among patients who have

increased liver enzymes with or without HCV risk factors, and 70% test

all patients who have risk factors regardless of liver enzyme levels. When

presented with a scenario on how to treat a hypothetical patient for chronic

HCV infection, 27% of the respondents did not know which therapy to use.

A previous study by the same researchers had also found substantial gaps in

primary care providers’ knowledge about hepatitis C (Shehab et al., 1999).

The gaps persisted even though 95% of the respondents in the 2001 study

reported having used at least one educational tool about hepatitis C in the

preceding 2 years; this suggests that primary care providers misreport their

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KNOWLEDGE AND AWARENESS ABOUT CHRONIC HEPATITIS B AND C 85

exposure to educational materials about hepatitis C or that such materials

do not communicate accurate information effectively.

HCV-positive patients perceive that health-care providers are judgmen-

tal toward those with HCV infection because of its association with illicit

drug use (Janke et al., 2008). Numerous studies have shown that health-

care workers have extremely negative views of IDUs and characterize them

as manipulative, unpleasant, and uncooperative (McLaughlin et al., 2000;

Paterson et al., 2007). Such attitudes among health-care providers can have

a number of deleterious effects, including discouraging of at-risk persons

from accessing testing and other services and reducing the effectiveness of

HCV education and counseling messages (Zickmund et al., 2003).

Additional research has examined HCV knowledge among drug-

treatment providers. Research conducted with 104 members of the staffsResearch conducted with 104 members of the staffs

of two drug-free and two methadone-maintenance treatment programs

(MMTPs) in the New York metropolitan area demonstrated that knowl-

edge about hepatitis C is inadequate (Strauss et al., 2006). Five of 20 items

on an HCV knowledge assessment were not answered correctly by the ma-

jority of the participating staff, suggesting that staff may be systematically

misinformed rather than merely uninformed about some important HCV

issues that affect their clients. Total scores on the assessment averaged 70%,

71%, and 45% among the medically credentialed staff, noncredentialed

staff in the MMTPs, and noncredentialed staff in the drug-free programs,

respectively. The majority of those in the latter group had never participated

in training speciﬁcally devoted to HCV; these staff may be sharing incorrect

information with patients or, aware of their limitations in HCV knowledge,

failing to provide patients much needed HCV information. It is critical that

both medically credentialed and noncredentialed staff in the programs re-

ceive effective HCV training so that they can support their patients’ HCV

education and information needs appropriately.

Recommendation

Many providers are not aware of the high prevalence of chronic hepa-

titis B and hepatitis C in some populations. Improved understanding of

risk factors for acute and chronic HBV and HCV infections and collection

of data on them, including country of birth and ethnicity, and the use of

risk-factor screening will lead to increased identiﬁcation of cases, increased

provision of preventive resources, increased vaccination to protect those at

risk for hepatitis B infection, and reduction in disparities in the burden of

chronic viral hepatitis.

On the basis of the evidence described above, the committee concludes

that insufﬁcient provider knowledge leads to critical missed opportunities

for providers to educate patients about prevention of hepatitis B and hepa-

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86 HEPATITIS AND LIVER CANCER

titis C, to identify patients who may be at risk for these infections, and to

test for chronic HBV and HCV infection in patients and their sexual, family,

and household contacts in the case of hepatitis B and in drug-use networks

in the case of hepatitis C. To address that issue, the committee offers the

following recommendation:

Recommendation 3-1. The Centers for Disease Control and Prevention

should work with key stakeholders (other federal agencies, state and

local governments, professional organizations, health-care organiza-

tions, and educational institutions) to develop hepatitis B and hepatitis

C educational programs for health-care and social-service providers.

Educational programs and materials for health-care and social-service

providers should focus on improving provider awareness and adherence to

practice guidelines for hepatitis B and hepatitis C. The educational programs

should be targeted to primary care providers, appropriate social-service

providers (such as staff of drug-treatment facilities and immigrant-services

centers), and licensed and unlicensed alternative-medicine professionals

(such as acupuncturists and traditional Chinese medicine practitioners) that

serve at-risk populations. At-risk populations include foreign-born people

from HBV- or HCV-endemic countries, clients of sexually-transmitted-

disease (STD) clinics and HIV clinics, IDUs, others at risk because of a

history of percutaneous exposures, and close contacts of people who have

chronic hepatitis B and chronic hepatitis C.

The educational programs should include at least the following

components:

• Information about the prevalence and incidence of acute and chronic

hepatitis B and hepatitis C both in the general US population and

in at-risk populations, particularly foreign-born populations in the

case of hepatitis B, and IDUs and incarcerated populations in the

case of hepatitis C.

• Guidance on screening for risk factors associated with hepatitis B

and hepatitis C.

• Information about hepatitis B and hepatitis C prevention, hepatitis

B immunization, and medical monitoring of chronically infected

patients, speciﬁcally,

o Information about methods of testing and interpretation of

results.

o Information about medical management and long-term care:

< How to select candidates for antiviral therapy.

< Importance of liver-cancer screening.

< When to refer patients to a specialist.

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KNOWLEDGE AND AWARENESS ABOUT CHRONIC HEPATITIS B AND C 87

• Information about prevention of HBV and HCV transmission in

hospital and nonhospital health-care settings.

• Information about discrimination and stigma associated with hepa-

titis B and hepatitis C and guidance on reducing them.

• Information about health disparities related to hepatitis B and

hepatitis C.

CDC should examine interventions that target several venues and

types of providers, such as educational institutions, health-care facilities,

substance-abuse service providers, and alternative-care providers.

Educational Institutions

Schools of medicine, nursing, physician assistants, complementary and

alternative medicine, and public health should develop improved curricula

to ensure that their graduates are knowledgeable about chronic hepatitis B

and hepatitis C. The curricula should include information on disease preva-

lence, risk factors, preventive actions, appropriate diagnostics, selection

of persons for testing, and appropriate followup for chronically infected

patients and those susceptible to infection.

Continuing-medical-education courses and activities about viral hepa-

titis conducted online or at provider meetings should be regularly offered

to family-practice physicians, internists, OB/GYNs, pediatricians, nurses,

and physician assistants. Drug-treatment counselors’ education and certiﬁ-

cation examinations should also include hepatitis B and hepatitis C. Ques-

tions about chronic hepatitis B should be included on board-certiﬁcation

or recertiﬁcation examinations for internists, family-practice physicians,

pediatricians, and OB/GYNs; and questions about chronic hepatitis C

should be included in board examinations for internists and family-practice

physicians. Although there has been no systematic effort to determine

whether continuing-medical-education courses and certiﬁcation examina-

tions include questions about hepatitis B and hepatitis C, the shortcomings

in knowledge among health-care providers suggest that current efforts are

insufﬁcient, and that new approaches are needed to improve knowledge.

Educational programs should include targeted outreach to and enroll-

ment of providers who work in high-risk venues (for example, STD and

HIV clinics) and in areas where there are many at-risk foreign-born clients,

such as hospitals, clinics, and community health centers that serve large

populations of Asian and Paciﬁc Islander (API) and foreign-born patients

from other highly endemic regions.

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88 HEPATITIS AND LIVER CANCER

Hospital and Other Health-Care Facilities

Health-care workers and their patients are at risk for exposure to

infected blood and body ﬂuids and therefore vulnerable to infection with

HBV and HCV. As discussed in Chapter 2, there have been several out-

breaks of hepatitis B and hepatitis C in health-care settings in recent years

(CDC, 2003b, 2003c, 2005, 2008a, 2009a; Fabrizi et al., 2008; Thompson

et al., 2009). Hospitals and nonhospital health-care facilities (such as di-

alysis units, endoscopy clinics, and long-term-care facilities) should develop

educational programs to reinforce the importance of adhering to recom-

mended standard precautions and procedures to prevent the transmission of

bloodborne infections in both inpatient and outpatient health-care settings

(Thompson et al., 2009). Health-care workers should be routinely vac-

cinated to protect them from hepatitis B. Although the ACIP recommends

that health-care workers receive the hepatitis B vaccine, and the Occupa-

tional Safety and Health Administration requires employers to offer the

hepatitis B vaccine to all health-care workers who may be exposed to blood

(29 CFR 1910.1030), about 25% of health-care workers remain unvacci-

nated (Simard et al., 2007). Successful interventions to prevent exposures

known to transmit bloodborne infections have included general safety train-

ing; training speciﬁc to prevention of needle-stick injuries; modiﬁcation of

practice, stafﬁng, and workload adjustments; and use of protective devices,

such as needles that automatically retract (Clarke et al., 2002; Holodnick

and Barkauskas, 2000; Hooper and Charney, 2005; Stringer et al., 2002;

Trim, 2004).

Substance-Abuse–Related Service Providers

Staff of drug-treatment programs, needle-exchange programs, and cor-

rectional facilities should be participants in viral-hepatitis educational pro-

grams. Studies have shown that IDUs who used needle-exchange programs

or who had been in drug treatment were more likely than others to report

their HCV-antibody status accurately (Hagan et al., 2006). Very high pro-

portions of IDUs have been in jail or prison (Milloy et al., 2008); therefore,

periods of incarceration may present a prime opportunity for providing

hepatitis C education to this high-risk population. In many communities

that have needle-exchange programs, the majority of IDUs have partici-

pated in them (Hagan et al., 1999; Lorvick et al., 2006). Over the period

during which a person may inject illicit drugs, the likelihood that he or she

has been in a drug-treatment program rises (Galai et al., 2003; Hagan et al.,

1999). Thus, the committee believes that providing standardized education

to staff of drug-treatment and needle-exchange programs and correctional

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KNOWLEDGE AND AWARENESS ABOUT CHRONIC HEPATITIS B AND C 89

facilities will increase the likelihood that at-risk and HCV-infected persons

in these settings receive consistent and accurate information.

Alternative-Care Providers

Alternative-care providers would also beneﬁt from participating in

educational programs about viral hepatitis. In California, four annual

educational symposia, in 2004–2007, were arranged by a collaboration of

academic, professional, and community-based organizations to improve

HBV-related knowledge among traditional Chinese medicine practitioners

and acupuncturists—providers who serve a largely API population, a pa-

tient population that has a high prevalence of chronic hepatitis B and the

associated risk of hepatocellular carcinoma (Chang et al., 2007). A pre-

course survey was administered; about half the participants did not know

ways to prevent HBV transmission, the age group most likely to develop

chronic infection, which blood test to use to diagnose chronic infection, or

the risk of death from liver disease or cancer in people who had chronic

hepatitis B. The postcourse survey showed a statistically signiﬁcant im-

provement in HBV-related knowledge: about 80% of participants were able

to answer questions about prevention and diagnosis of and treatment for

HBV infection correctly.

COMMUNITY KNOWLEDGE AND AWARENESS

The committee has found that knowledge and awareness about hepa-

titis B and hepatitis C are lacking in members of the public and, most im-

portant, in members of speciﬁc at-risk populations. Lack of knowledge and

awareness about hepatitis B and hepatitis C in the community often leads

to misinformation, missing of opportunities for prevention and treatment,

and stigmatization of infected populations. The consequences for members

of at-risk communities are important in that missing opportunities for

prevention can lead to infection of additional people with HBV and HCV.

Once infected, they frequently are unaware of their infection and so run

the risk of unknowingly infecting others and of not receiving appropriate

medical management. Although there have been no large-scale, population-

based, controlled studies of community knowledge about hepatitis B and

hepatitis C, all published surveys have shown that knowledge about these

diseases is sparse.

Hepatitis B

As mentioned earlier, APIs are at high risk for chronic hepatitis B. A

number of studies have assessed awareness and knowledge about hepatitis B

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90 HEPATITIS AND LIVER CANCER

in API populations, including Vietnamese, Cambodian, Korean, and Chinese

Americans, who are known to have a higher prevalence of chronic HBV

infection than the general US population (Hwang et al., 2008; Ma et al.,

2007b, 2008; Taylor, 2006; Taylor et al., 2000, 2002, 2004, 2005a, 2005b;

Thompson et al., 2002; Wu et al., 2007). For example, among Vietnamese

Americans, about 64% had never heard of the hepatitis B vaccine (Ma et

al., 2007b), about 70% were unaware that Asian Americans are at high risk

for chronic hepatitis B (Hwang et al., 2008), most were uninformed about

routes of HBV transmission (Taylor et al., 2000, 2005a, 2005b), and only

one-third had a doctor’s recommendation to undergo HBV testing (Taylor

et al., 2004). In populations of low socioeconomic status, fewer than 10%

had been tested for or vaccinated against HBV (Ma et al., 2007a, 2007b).

In a group of Cambodian Americans, fewer than 50% had ever heard of

or been tested for HBV, and fewer than 25% knew that chronic infection

is lifelong and incurable (Taylor et al., 2002).

Misinformation about HBV transmission creates obstacles for pre-

vention and treatment. In qualitative interviews, most Korean Americans

expressed the belief that sharing of contaminated food and eating utensils

was the most common route of HBV transmission, whereas few mentioned

that HBV can be sexually or parenterally transmitted, and none mentioned

vertical mother-to-child transmission (Choe et al., 2005). Among Chinese

Americans, fewer than half had been tested or vaccinated (Taylor et al.,

2006; Thompson et al., 2002), up to 53% believed HBV could be trans-

mitted by contaminated food (Wu et al., 2007), up to 61% were unaware

that chronic hepatitis B is typically asymptomatic, and 46% believed that

there is a curative treatment for chronic hepatitis B (Wu et al., 2007); about

65% of those who were chronically infected were unaware of their infection

status (Lin et al., 2007).

The committee was unable to ﬁnd studies that looked at hepatitis B

awareness among other foreign-born immigrants from highly endemic re-

gions such as sub-Saharan Africa, the Middle East, and Eastern European

nations (see Box 3-1). Some educational resources have been translated into

a few languages. For example, New York City has translated its hepatitis

B educational materials into Chinese, Korean, Spanish, and French (New

York Department of Health and Mental Hygiene, 2008).

The incarcerated population has a high risk of being infected with HBV.

About 30% of patients who had acute hepatitis B reported a history of

incarceration before HBV infection (Charuvastra et al., 2001; Goldstein et

al., 2002). Knowledge about HBV transmission in this population is poor

and results in missing of opportunities for vaccination and prevention. A

voluntary, anonymous survey of 153 male and female inmates of the Rhode

Island Department of Corrections revealed that over half the 30% who

reported having risk factors for HBV infection did not consider themselves

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KNOWLEDGE AND AWARENESS ABOUT CHRONIC HEPATITIS B AND C 91

to be at risk for hepatitis B (Vallabhaneni et al., 2004), and 44% of the

inmates were not aware that HBV can be transmitted through unprotected

sexual activity.

Several studies have found that knowledge about hepatitis B is low

among men who have sex with men, another population at high risk for

HBV infection (McCusker et al., 1990; Neighbors et al., 1999; Rhodes et

al., 2000). A 1990 study found that 68% of men who have sex with men

and are patients at a community health center reported that they were

aware of the vaccine, and 25% of those who knew about it had been vac-

cinated (McCusker et al., 1990). Most of the participants who knew about

the hepatitis B vaccine had learned about it from newspapers targeting the

gay population (64%); a minority had learned about it from health-care

providers (44%), friends (37%), and brochures from health-care facilities

or gay organizations (36%). A 1999 study had similar ﬁndings: 33% of

the participants were unaware of the hepatitis B vaccine, and 63% had not

been tested for hepatitis B; of those who were aware of the vaccine, only

22% had received the full vaccine series (Neighbors et al., 1999). A simi-

larly low level of hepatitis B knowledge was found among patrons of gay

bars in Birmingham, Alabama, where 32% reported having no information

about hepatitis, 96% reported engaging in high-risk sexual behavior, and

those who had not been vaccinated against HBV (58% of respondents) had

much poorer knowledge about hepatitis B prevention than those who had

been vaccinated (Rhodes et al., 2000).

Stigma

For many people born outside the United States, a cultural stigma is

attached to a diagnosis of chronic hepatitis B. For example, in China, there

is pervasive discrimination against people who are chronically infected

with hepatitis B, who are frequently expelled from schools, ﬁred from jobs,

and shunned by other community members despite the recent passage of

national antidiscrimination laws (China Digital Times, 2009). In a 2007

survey covering 10 major cities in China, hepatitis B was cited as one of

the top three reasons for job discrimination (China Daily, 2007). Given

the deeply ingrained stigma of hepatitis B in some endemic countries, it is

not surprising that many immigrants remain reluctant to undergo testing

and seek medical attention for a positive test result even after moving to

the United States. Because that cultural aversion to hepatitis B testing and

management is due largely to a lack of knowledge about routes of HBV

transmission and means of prevention, any effort to deliver viral-hepatitis

services to the foreign-born population must include an educational com-

ponent to dispel myths (for example, that HBV can be transmitted through

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92 HEPATITIS AND LIVER CANCER

food, water, and casual contact) and to establish facts, particularly ones

that encourage testing, vaccination, and followup.

Education Programs

Several educational programs targeting API communities have been

successful in disseminating hepatitis B awareness and promoting preven-

tion. Successful programs often build on community partnerships and com-

bine educational resources with increased access to testing, prevention, and

care for participants (CDC, 2006; Chao et al., 2009a; Juon et al., 2008; Lin

et al., 2007). The Hepatitis B Initiative is a community-based hepatitis B

outreach program that partnered with nine Korean American and Chinese

American churches in the Baltimore and Washington, DC, metropolitan

area to provide culturally and linguistically tailored, faith-based HBV edu-

cation, testing, and vaccination (Juon et al., 2008). The initiative has gener-

ated community support and awareness through word of mouth, articles in

local Asian ethnic media, educational sessions and luncheons for API com-

munity leaders, and a national conference for API pastors. In 2003–2006,

the program tested 1,775 participants for HBV and found that 2% were

chronically infected and 61% were not vaccinated. Among 924 unvacci-

nated participants, nearly all received the ﬁrst dose of hepatitis B vaccine,

89% received the second, and 79% completed the three-dose series. The

Asian American Hepatitis B Program, a collaboration of community groups

and academic and community health centers in New York City, provides

hepatitis B screening, vaccination, and treatment. The program found that

about 15% of newly tested persons had chronic HBV infection, all of whom

were born outside the United States and half of whom had been in the

country for more than 10 years (CDC, 2006).

The Jade Ribbon Campaign is a program focused on reducing the

nationwide health disparity in hepatitis B. This program sponsors com-

munity HBV screening and education clinics and partners with over 400

community-based organizations and federal and state agencies to provide

culturally and linguistically tailored information and multimedia public-

service announcements about hepatitis B burden, risk factors, transmis-

sion, prevention, detection, treatment, and followup to the API community

and health professionals (Asian Liver Center, 2009; CDC, 2009b). The

program’s clinics have found that about 45% of participants were not

vaccinated against HBV, 9–13% of participants were chronically infected,

and up to two-thirds of those who were chronically infected were unaware

of their infection status. Of those who said that they had been vaccinated

against HBV, 20% were unprotected and 5% chronically infected (Chao et

al., 2009a; Lin et al., 2007). This model has been adapted by a number of

cities around the country (Chang et al., 2009; Fernandez, 2008; Hsu et al.,

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KNOWLEDGE AND AWARENESS ABOUT CHRONIC HEPATITIS B AND C 93

2007; Larkin, 2007; McBride, 2008; San Francisco HepB Free, 2009; Tsai

et al., 2008; Zola et al., 2009).

As discussed in Chapter 4, the ACIP recommends that all newborns,

previously unvaccinated children and adolescents, and previously unvac-

cinated adults at high risk for infection be vaccinated against hepatitis

B (Mast et al., 2005, 2006). The latter group includes adults at risk for

infection by sexual exposure, IDUs, household contacts of chronically

infected persons, developmentally disabled persons in long-term-care fa-

cilities, persons at risk for occupational exposure to HBV, hemodialysis

patients, persons with chronic liver disease, and travelers to HBV-endemic

regions, including Asia, Africa, much of Eastern Europe, the Amazon Basin,

the Caribbean, and the Paciﬁc Islands (see Box 4-1). There is a shortage

of hepatitis B education, vaccine promotion, and awareness programs for

nearly all those at-risk populations, and programs need to be developed to

target HIV-positive people, IDUs, and people from highly HBV-endemic

regions (Rein et al., 2009). Although a handful of studies have evaluated

cross-sectional hepatitis B knowledge levels in some of the populations, the

committee knows of no programs that have demonstrated a quantitative

improvement in knowledge about hepatitis B after the implementation of a

targeted, evidence-based educational program.

A potential model to target at-risk populations is to develop pilot sites

similar to CDC’s Racial and Ethnic Approaches to Community Health,

REACH 2010. The REACH 2010 program provided grants to communi-

ties to address services for speciﬁed illnesses in particular racial and ethnic

populations. The program targeted blacks, American Indians, Alaska Na-

tives, Asian Americans, Hispanics, and Paciﬁc Islanders—all populations

that have a high prevalence or incidence of hepatitis B and some hepatitis C

also. Viral hepatitis was not part of the program (Collins, 2006; Giles et

al., 2004).

Hepatitis C

Although fewer studies have been conducted to assess awareness of

hepatitis C in speciﬁc populations, the literature suggests that knowledge

about this disease is poor. In a cohort of 3,768 women who had or were at

risk for HIV infection, about one-fourth of those with chronic HCV infec-

tion were not aware of their infection status (Cohen et al., 2007). Younger

and black women were less likely to be aware of their HCV infection status,

whereas women who had past alcohol treatment, a history of injection-drug

use, or increased alanine aminotransferase (a liver enzyme) were more likely

to be aware that they were positive for HCV infection. Of those aware of

their chronic HCV infection, the health-care providers of 47% had recom-

mended that they have a liver biopsy, and 56% of these had undergone a

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94 HEPATITIS AND LIVER CANCER

biopsy; 39% of those who were aware of their HCV infection status had

been offered treatment, and 57% of these had received treatment.

Similarly, in the Collaborative Injection Drug User Study Drug User In-

tervention Trial (DUIT), which enrolled 3,004 young IDUs in ﬁve US cities,

72% of anti-HCV-positive and 46% of anti-HCV-negative IDUs were not

aware of their HCV serologic status (Hagan et al., 2006). History of drug

treatment or needle exchange was associated with increased awareness of

HCV serologic status, so these programs may be key locations for provision

of HCV screening in this population. In a questionnaire survey given to 150

patients who were seeking substance-abuse treatment at a Department of

Veterans Affairs medical center, 90% of patients who were HCV-infected

were not aware of their status, and 41% of the IDUs did not know or were

unsure of how HCV is transmitted or about the complications of hepatitis

C (Dhopesh et al., 2000)..

Stein et al. (2001) surveyed 306 former IDUs about their knowledge of

HCV transmission, infection status, and risk of liver disease. They foundThey found

that nearly all the participants knew that HCV is transmitted by sharing

contaminated needles. Among people who had not been tested or did not

know their test results, some 82% were HCV seropositive. One-third of the

people reporting that they were seronegative were actually seropositive—a

demonstration that, as in other surveys, self-reported infection status is

unreliable. Of respondents, 81% estimated their risk of developing liver

disease, speciﬁcally cirrhosis, in the next 10 years at 50% or greater.

The risk associated with the shared use of injection paraphernalia other

than syringes is poorly understood (Rhodes et al., 2004). Among IDUs who

have chronic HCV infection and are aware of their infection, the pattern is

similar: the majority understand that they can transmit their infection by

passing on their used syringes to others, but there is less certainty regarding

the shared use of cookers, cottons, and rinse water (Rhodes and Treloar,

2008; Wright et al., 2005).

There is substantial confusion among IDUs regarding the interpretation

of HCV screening tests. In an Australian study, 42% of IDUs believed that

being antibody-positive meant that they were immune to HCV infection

(O’Brien et al., 2008). Misunderstanding of the meaning of antibody-test

results was also observed in a qualitative study of IDUs in London, England

(Rhodes et al., 2004).

Stigma

A number of studies have examined the psychologic consequences of

HCV infection and concluded that hepatitis C is a highly stigmatized dis-

ease, owing in large part to its association with injection-drug use (Conrad

et al., 2006; Crofts et al., 1997; Dunne and Quayle, 2001; Grundy and

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KNOWLEDGE AND AWARENESS ABOUT CHRONIC HEPATITIS B AND C 95

Beeching, 2004). There is also a public perception that HCV is highly con-

tagious and that it is life-threatening in most cases (Conrad et al., 2006);

this has led to discrimination on the part of people who inappropriately

perceive themselves to be at risk from casual contact with an HCV-positive

person. In a study of patients in a liver clinic in Iowa, 57% of HCV-positive

people reported having experienced stigma associated with their infection

(Zickmund et al., 2003). Many patients who have HCV infection wish to

disclose their HCV status to family, intimate partners, and others in an

effort to protect them from infection and to obtain psychosocial support.

Even in work settings, people have been eager to disclose their HCV status

so that in the event of injury co-workers would take extra care in avoid-

ing exposure to contaminated blood. However, many people report that

informing others of their HCV status has led to inappropriate reactions,

such as “[I’m] not allowed to use the cups because they don’t really know

. . . how to pass it on” (Conrad et al., 2006). In another study, a patient

reported that “they didn’t want me drinking out of the water fountain”

(Zickmund et al., 2003).

Education Programs

Although only a handful of studies have examined the inﬂuence of edu-

cation on HCV-related risk behavior in IDUs, the results are consistent in

showing that enhanced education and counseling are associated with safer

injection practices (Garfein et al., 2007; Latka et al., 2008; Tucker et al.,

2004). In the DUIT study by Garfein et al. (2007), young HIV-seronegative

and HCV-seronegative IDUs were enrolled in a randomized trial of an inter-

vention that sought to train them to be peer educators. The goals of the

peer-education intervention (PEI) were to develop mastery over knowledge

and skills necessary for prevention of HIV and HCV infection so that they

could pass the knowledge on to their peers. Behavior change was measured

in the PEI subjects and in subjects randomized to an equal-attention control

group. Reductions in injection risk behavior were observed in both study

arms, but the PEI group reported signiﬁcantly greater reductions.

A parallel study, the Study to Reduce Intravenous Exposures (STRIVE),

enrolled young HCV-seropositive IDUs (most of whom were chronically

infected) and randomized them into a PEI or control condition. Signiﬁcantly

greater reductions in injection practices that could transmit HCV to other

IDUs were observed in the PEI group (Latka et al., 2008). Thus, enhanced

education and skill-building can lead to safer injection practices and may

contribute to avoidance of infection in susceptible IDUs and reduction in

transmission of infection to other IDUs. That strategy parallels the Preven-

tion for Positives initiatives for HIV (CDC, 2003a).

Patients in drug-treatment programs have considerable needs for educa-

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96 HEPATITIS AND LIVER CANCER

tion about hepatitis C. In spite of the disproportionate prevalence of HCV

infection in drug users, research conducted with 280 patients who never

injected drugs (non-injection-drug users, NIDUs) and past or current IDUs

in 14 US drug-treatment programs showed that many remain uninformed

or misinformed about the disease (Strauss et al., 2007). The 280 partici-

pating patients scored, on the average, 56% on a 20-item true–false HCV

knowledge assessment, demonstrating inadequate knowledge about hepa-

titis C. IDUs scored signiﬁcantly higher, on the average, than did NIDUs

(60% vs 51%), but their scores also suggest many gaps in their knowledge

about hepatitis C. Fewer than half of all the patients correctly endorsed

facts concerning HCV transmission, the duration of hepatitis C treatment,

the potential effectiveness of hepatitis C medication in active drug users,

the course of HCV infection, and the possibility of spontaneous clearance

of the infection.

To address the knowledge gaps, all the programs offered at least one

form of hepatitis C education: all offered one-on-one sessions with staff,

12 of the programs offered hepatitis C education in a group format, and

11 offered education through pamphlets and books. However, only 60% of

all the participating patients used any of their programs’ hepatitis C educa-

tion services. Those who did avail themselves of the hepatitis C education

opportunities generally assessed them favorably. Of all the patients, many

were unaware that hepatitis C education was offered in their programs

through individual sessions with staff, group meetings, and books and pam-

phlets (42%, 49%, and 46% of the patients, respectively), and 22% were

unaware that any hepatitis C education opportunities existed (Strauss et al.,

2007). Thus, efforts need to focus especially on ensuring that all drug-treat-

ment program patients are made aware of and encouraged to use hepatitis

C education services in their programs. Such awareness and encouragement,

however, will be useful only if staff of drug-treatment programs have up-

to-date knowledge about the virus and treatment options so that they can

share hepatitis C information with their patients accurately.

Recommendation

On the basis of the above ﬁndings, the committee offers the follow-

ing recommendation to increase educational and awareness opportunities

about hepatitis B and hepatitis C.

Recommendation 3-2. The Centers for Disease Control and Prevention

should work with key stakeholders to develop, coordinate, and evalu-

ate innovative and effective outreach and education programs to target

at-risk populations and to increase awareness in the general population

about hepatitis B and hepatitis C.

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KNOWLEDGE AND AWARENESS ABOUT CHRONIC HEPATITIS B AND C 97

CDC should work with other federal agencies and state and local

governments to form partnerships with health-care providers, private or-

ganizations (including employers and nonproﬁt organizations), schools,

and appropriate community organizations to develop awareness programs

and campaigns to educate the general public and at-risk populations about

hepatitis B and hepatitis C. The programs should include shared resources

that are linguistically and culturally appropriate and support integration of

education about viral hepatitis and liver health into other health programs

that serve at-risk populations. Successful programs like those discussed

above should serve as models for interventions and existing materials, such

as the American Congress of Obstetricians and Gynecologists patient edu-

cation materials on viral hepatitis (American College of Obstetricians and

Gynecologists, 2007, 2008, 2009), should be used as a basis for producing

linguistically and culturally relevant materials.

Innovative approaches should be developed to address populations that

have access to few educational programs including foreign-born people

from the highly HBV endemic regions, men who have sex with men, IDUs,

and household and sexual contacts of people who are chronically infected

with HBV and HCV.

Programs should be evaluated to ensure that they are effectively tar-

geting the general public and at-risk people and populations. The general

public should be targeted because HBV and HCV infections occur in people

not easily identiﬁable as belonging to an at-risk population or people who

fail to report potential risk factors (Daniels et al., 2009). The results of

evaluation of the programs will inform future initiatives. The programs

should incorporate interventions that meet the following goals:

• Promote better understanding of HBV and HCV infections,

transmission, prevention, and treatment in at-risk and general

populations.

• Promote increased hepatitis B vaccination rates among children

and at-risk adults.

• Educate pregnant women and women of childbearing age about

hepatitis B prevention.

• Reduce perinatal HBV infections and improvement of at-birth im-

munization rates.

• Increase testing rates in at-risk populations.

• Reduce stigmatization of chronically infected people.

• Promote safe injections among IDUs and safe drug use among

NIDUs.

• Provide culturally and linguistically appropriate educational infor-

mation for all persons who have tested positive for chronic HBV or

HCV infections and those who are receiving treatment.

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98 HEPATITIS AND LIVER CANCER

• Encourage notiﬁcation of household and sexual contacts of infected

people to be tested for HBV and HCV and encourage hepatitis B

vaccination of close contacts.

General Public Awareness and Education

Lack of knowledge about HBV and HCV transmission contributes to

the stigma of infection and is a barrier to testing, prevention, and care.

Public HIV-awareness campaigns led to reduced stigma and discrimina-

tion toward patients with HIV infection (Brown et al., 2003). As in the

case of HIV/AIDS, increasing general public knowledge about hepatitis B

and hepatitis C can be expected to reduce discrimination toward infected

people, reduce transmission, and increase early diagnosis and treatment

that ultimately save lives.

Broader community education should include print and multimedia

educational materials about viral hepatitis for the public, large employers,

and health insurers. It should work to mobilize and facilitate a grassroots

movement among community stakeholders, including health-care provid-

ers, employers, mainstream and ethnic media, community-based organiza-

tions, and students. Large employers, such as multinational corporations,

are potentially important partners in hepatitis prevention and control in

that they provide health beneﬁts to about two-thirds of Americans who

have health insurance and are commonly employers of foreign-born people

from HBV-endemic countries both in the United States and overseas.

The lack of knowledge and awareness about hepatitis B and hepatitis

C in the general population suggests that integration of viral-hepatitis and

liver-health education into existing health-education curricula in schools

will help to eliminate the stigma of those chronically infected and improve

prevention of viral hepatitis. There is evidence that adolescents are unaware

of hepatitis B and hepatitis C risks and how to prevent becoming infected

(Moore-Caldwell et al., 1997; Slonim et al., 2005). Many schools already

require health education on HIV, which has transmission routes similar to

those of hepatitis B and hepatitis C (CDC, 2008b). Several school-based

programs have been demonstrated to reduce HIV risk in students and could

serve as models for viral hepatitis education initiatives (Gaydos et al., 2008;

Kennedy et al., 2000).

Community-Based Outreach to Foreign-Born

Immigrants from HBV-endemic countries make up the largest popula-

tion of people who have chronic hepatitis B in the United States, and it is

essential that they receive culturally and linguistically tailored information

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KNOWLEDGE AND AWARENESS ABOUT CHRONIC HEPATITIS B AND C 99

about transmission and risks of HBV infection and that it promote testing,

vaccination, and medical management.

Rein et al. (2009) estimated that there are 55 active community-based

hepatitis B outreach programs in the country that were targeting mostly

APIs, of which they contacted 31. Although those programs have done

much to inform APIs about hepatitis B, there is a need for additional

programs that target APIs, given the burden of hepatitis B within that

population.

There is also a need for education programs that target foreign-born

people from other HBV-endemic regions. The models used by programs de-

signed for APIs could be modiﬁed to address the needs of other populations.

Community-based education and screening programs—including outreach

at cultural festivals, health fairs, and places of worship—have been shown

to be effective in improving APIs’ knowledge about hepatitis B (Chao et

al., 2009a; Hsu et al., 2007; Juon et al., 2008; Lin et al., 2007) and could

potentially be effective with other ethnic populations. Each year, around

20,000 people are tested through those programs, and HBsAg is detected

in about 8% of the tested population (Rein et al., 2009). Some 30% of the

programs were supported by local government funding, 27% by state fund-

ing, and 10% by federal funding. Other sources include pharmaceutical and

insurance companies, research and service grants, community hospitals, and

other private funding sources (Rein et al., 2009).

Rein et al. (2009) also found that there were few or no hepatitis B

outreach programs in most regions of the United States (the Southeast, the

Midwest, and the Southwest outside of California and the Houston area).

Education and prevention programs should be expanded to provide services

in underserved regions of the United States given that the highest rates of

acute hepatitis B incidence are in the south (Daniels et al., 2009).

Correctional Facilities

About 2 million people are incarcerated in the US correctional system.

The major risk factors for viral hepatitis in people in correctional facilities

are injection-drug use, tattooing, and sexual activity (see Chapters 4 and 5

for additional information about incarcerated populations). Because people

in the correctional system are more likely to be infected or to become in-

fected with HBV and HCV than the US general population, it is important

to provide educational opportunities about hepatitis B and hepatitis C in

correctional facilities. Increased knowledge and awareness about the dis-

eases will lead to a greater understanding among inmates about how to

prevent them, the advantages of hepatitis B vaccination, why they should

be tested for chronic hepatitis B and hepatitis C, and what to do about a

positive test result for either infection. Niveau (2006) reviewed risk factors

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100 HEPATITIS AND LIVER CANCER

for acquiring infectious diseases in correctional settings and found that

effective preventive measures included information dissemination and edu-

cation. Inmate peer-based health education has been effective in primary

prevention of HIV (Hammett, 2006). The addition of hepatitis education to

existing peer-based inmate educational programs is feasible and will prob-

ably incur minimal additional cost. Boutwell et al. (2005) called education

of prisoners about hepatitis C as part of a larger program of prevention,

testing, and treatment a “cornerstone of the public health response to the

hepatitis C epidemic in the United States” and recommended research into

program implementation.

Drug-Treatment Facilities and Needle-Exchange Programs

Drug-treatment and needle-exchange programs reach a substantial pro-

portion of active injectors who have HCV infection or are at risk of acquir-

ing it. Because the programs have regular, long-term contact with many

IDUs, there are multiple opportunities to disseminate information about

hepatitis B and hepatitis C, including the beneﬁts of hepatitis B vaccination,

how to avoid reinfection with HCV, and the importance of followup care

for those chronically infected.

Although education programs developed for needle exchange, drug

treatment, and corrections facilities will reach substantial proportions of

those at risk, important segments of IDU populations will not be reached by

them. Women and young people who inject drugs are less likely than others

to attend needle-exchange and drug-treatment programs (Bluthenthal et al.,

2000; Miller et al., 2001). Novel programs are needed that will access the

hidden injectors, and outreach and peer-education programs are potentially

effective ways to achieve this goal.

Perinatal Facilities That Care for Pregnant Women

The risk of chronic infection after exposure to HBV is highest in early

life, and most people who have chronic hepatitis B were infected at birth

or during early childhood. Each year in the United States, about 24,000

HBsAg-positive women give birth and about 1,000 newborns develop

chronic HBV infection (Ward, 2008). The latter occurs largely because of

failure to adhere to ACIP recommendations and timely administration of

the birth dose of the hepatitis B vaccine and hepatitis B immunoglobulin.

Although it is recommended that household contacts be tested because

of high risk of infection, fewer than 50% are tested, and fewer than 50%

of those tested and found to be HBV-negative or of unknown status are

vaccinated (Euler et al., 2003a). Therefore, perinatal-care facilities and their

staffs (including OB/GYNs and their clinic staffs) provide an excellent op-

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KNOWLEDGE AND AWARENESS ABOUT CHRONIC HEPATITIS B AND C 101

portunity to educate pregnant women about the importance of HBsAg test-

ing, interpretation of the results, and the importance of newborn hepatitis

B vaccination. The women should be given culturally and linguistically ap-

propriate educational information about the importance of administration

of the birth dose of the hepatitis B vaccine and hepatitis B immunoglobulin

within 12 hours of birth if needed, completion of the hepatitis B vaccine

series by the age of 6 months, and postvaccination testing. There is a need

to develop a novel program to educate pregnant women in perinatal-care

facilities about hepatitis B to prevent perinatal transmission, to refer women

who are chronically infected for medical care, and to refer family and

household contacts for testing, vaccination, and care if needed.

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109

Immunization

epatitis B is a vaccine-preventable disease for which a safe and ef-

fective vaccine has been available for nearly three decades. The ﬁrst

part of this chapter reviews current federal vaccination recommenda-

tions and state vaccination requirements for hepatitis B. It also summarizes

what is known about hepatitis B vaccination rates in speciﬁc populations

(for example, infants, children, and adults, including subgroups of at-risk

adults, such as incarcerated people and occupationally exposed people).

The committee identiﬁed missed opportunities for hepatitis B vaccination

and makes recommendations to increase the vaccination rate among vari-

ous populations.

A vaccine for hepatitis C does not exist. The second part of this chapter

summarizes current efforts to develop a hepatitis C vaccine and challenges

that have been encountered. The committee makes a recommendation

about hepatitis C vaccine development.

HEPATITIS B VACCINE

The ﬁrst hepatitis B vaccine, a plasma-derived vaccine, was licensed by

the US Food and Drug Administration (FDA) in 1981 (IOM, 1994). By the

late 1980s, the plasma-derived vaccine was replaced with a recombinant

version, which expresses the hepatitis B surface antigen (HBsAg) and is

produced in Saccharomyces cerevisiae (common baker’s yeast). The recom-

binant vaccine was licensed by FDA in 1986 and is the type of hepatitis B

vaccine currently used in the United States. It is an anticancer vaccine: by

preventing hepatitis B, it prevents hepatocellular carcinoma.

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110 HEPATITIS AND LIVER CANCER

Hepatitis B vaccine is available both as single-antigen formulations

and as multiantigen formulations in ﬁxed combination with other vac-

cines (Mast et al., 2005). The two single-antigen vaccines are Recom-

bivax HB

(Merck & Co., Inc., Whitehouse Station, NJ) and Engerix-B

(GlaxoSmithKline Biologicals, Rixensart, Belgium). Of the three licensed

combination vaccines, Twinrix

(GlaxoSmithKline Biologicals, Rixensart,

Belgium) is used for vaccination of adults, and Comvax

(Merck & Co.,

Inc., Whitehouse Station, NJ) and Pediarix

(GlaxoSmithKline Biologicals,

Rixensart, Belgium) are used for vaccination of infants and young children.

Twinrix contains recombinant HBsAg and inactivated hepatitis A virus.

Comvax contains recombinant HBsAg and Haemophilus inﬂuenzae type

b (Hib) polyribosylribitol phosphate conjugated to Neisseria meningitidis

outer-membrane protein complex. Pediarix contains recombinant HBsAg,

diphtheria and tetanus toxoids and acellular pertussis adsorbed (DTaP),

and inactivated poliovirus.

The hepatitis B vaccine is administered in a three-dose series: two

priming doses administered 1 month apart and a third dose administered 6

months after the second (Mast and Ward, 2008). Alternative schedules have

been used successfully. Administration of the three-dose series results in

protective concentrations of anti-HBs in more than 95% of healthy infants,

children, and adolescents and in more than 90% of healthy adults aged 40

years old and younger. Immunogenicity drops below 90% in adults over

the age of 40 years. The hepatitis B vaccine has a pre-exposure efﬁcacy of

80–100% and a postexposure efﬁcacy of 70–95%, depending on whether

hepatitis B immune globulin (HBIG) is given with the vaccine. The duration

of immunity appears to be long-lasting, and booster doses of the vaccine

are not routinely recommended (Mast and Ward, 2008).

HBIG is derived from plasma and is used prophylactically to prevent

infection with the hepatitis B virus (HBV). It provides passively acquired

antibody to hepatitis B surface antigen (anti-HBsAg) and temporary protec-

tion (3–6 months). HBIG is typically used as an adjunct to hepatitis B vac-

cine for postexposure immunoprophylaxis to prevent HBV infection (Mast

et al., 2005). HBIG administered alone is the primary means of protection

after an HBV exposure for people who do not respond to hepatitis B vac-

cination. It is also used after liver transplantation for end-stage hepatitis B

to prevent recurrence of the disease in the transplanted liver.

Current Vaccination Recommendations, Requirements, and Rates

The Advisory Committee on Immunization Practices (ACIP) provides

advice and guidance to the US Department of Health and Human Services

and the US Centers for Disease Control and Prevention (CDC) on the con-

trol of vaccine-preventable diseases. It develops written recommendations

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IMMUNIZATION 111

for the routine administration of vaccines to children and adults in the

civilian population. The ACIP recommendations for who should receive

the hepatitis B vaccine are summarized in Box 4-1. The American Academy

of Pediatrics in its Report of the Committee on Infectious Diseases follows

the ACIP recommendations for the hepatitis B vaccine (American Academy

of Pediatrics, 2009).

Perinatal Vaccination

ACIP ﬁrst recommended universal hepatitis B vaccination of infants in

1991 (ACIP, 1991). Despite the recommendation, each year about 1,000

newborns in the United States acquire chronic HBV infection (Ward, 2008),

a number that has not declined in the last decade. That constitutes an im-

portant gap that needs to be addressed in future prevention efforts.

ACIP currently recommends that the ﬁrst dose—that is, the birth

dose—be administered before hospital discharge in infants born to HbsAg-

negative women and within 12 hours of birth in infants born to women

who are HbsAg-positive or of unknown status (Mast et al., 2005). It also

recommends that infants born to HBsAg-positive mothers should be given

HBIG within 12 hours of birth. There is no evidence of appreciable ben-

eﬁt if HBIG is administered more than 72 hours after birth. The timely

identiﬁcation of HBsAg-positive mothers to prevent perinatal transmis-

sion underscores the need for rapid hepatitis B tests (discussed further in

Chapter 5). The hepatitis B vaccine series should be completed by the age

of 18 months (see Table 4-1). Depending on which type of vaccine (single-

antigen or combination) is administered, the series can consist of three or

four vaccinations.

Current ACIP hepatitis B vaccine recommendations for preterm infants

who weigh less than 2,000 g are summarized in Table 4-2. For preterm

infants, the ﬁrst dose of the vaccine is given within 12 hours of birth if the

mother is HBsAg-positive or is of unknown status. If the mother is known

to be HbsAg-negative, the ﬁrst dose is administered at the age of 1 month

or at hospital discharge (Mast et al., 2005). The preterm-infant schedule is

based on the recognition that preterm infants have a decreased response to

hepatitis B vaccine administered before the age of 1 month.

Data from National Immunization Surveys demonstrate that national

newborn hepatitis B vaccination coverage did not change appreciably after

implementation of the 2005 ACIP hepatitis B vaccination recommenda-

tion (CDC, 2009b). Using National Immunization Survey data that were

collected before implementation of the 2005 ACIP hepatitis B vaccination

recommendation, CDC estimated that the national newborn hepatitis B

vaccination coverage was 46%, 47.9%, and 42.8% at the age of 1 day

in the 2004, 2005, and 2006 surveys (CDC, 2008c, 2009b). Using data

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112 HEPATITIS AND LIVER CANCER

BOX 4-1

Summary of ACIP Hepatitis B Vaccination Recommendations

Vaccination of infants

At birth

• Infants born to mothers who are HbsAg-positive should receive hepa-

titis B vaccine and HBIG within 12 hours of birth.

• Infants born to mothers whose HBsAg status is unknown should re-

ceive hepatitis B vaccine within 12 hours of birth. The mother should

have blood drawn as soon as possible to determine her HBsAg status;

if she is HbsAg-positive, the infant should receive HBIG as soon as

possible (no later than the age of 1 week).

• Full-term infants who are medically stable, weigh over 2,000 g, and

are born to HBsAg-negative mothers should receive single-antigen

hepatitis B vaccine before hospital discharge.

• Preterm infants weighing less than 2,000 g and born to HbsAg-

negative mothers should receive the ﬁrst dose of vaccine 1 month

after birth or at hospital discharge.

After the birth dose

• All infants should complete the hepatitis B vaccine series with either

single-antigen vaccine or combination vaccine according to a recom-

mended vaccination schedule.

• Infants born to HBsAg-positive mothers should be tested for HBsAg

and antibody to HBsAg after completion of the hepatitis B vaccine

series at the age of 9–18 months.

Vaccination of children and adolescents

• All unvaccinated children and adolescents less than 19 years old

should receive the hepatitis B vaccine series.

Vaccination of adults

Persons at risk for infection by sexual exposure

• Sex partners of HbsAg-positive persons.

• Sexually active persons who are not in a long-term, mutually mo-

nogamous relationship (for example, persons with more than one sex

partner during the previous 6 months).

• Persons seeking evaluation or treatment for a sexually transmitted

disease.

• Men who have sex with men.

Persons at risk for infection by percutaneous or mucosal exposure to

blood

• Current or recent injection-drug users.

• Household contacts of HBsAg-positive persons.

• Residents and staff of facilities for developmentally disabled

persons.

• Health-care and public-safety workers who have a reasonably antici-

pated risk of exposure to blood or blood-contaminated body ﬂuids.

• Persons with end-stage renal disease, including predialysis, hemodi-

alysis, peritoneal-dialysis, and home-dialysis patients.

• Incarcerated persons.

Others

• International travelers to regions that have high or intermediate levels

(HBsAg prevalence of at least 2%) of endemic HBV infection.

• Persons who have chronic liver disease.

• Persons who have HIV infection.

• All other persons who are seeking protection from HBV infection.

Abbreviations: ACIP, Advisory Committee on Immunization Practices; HBsAg, hepatitis B

surface antigen; HBIG, hepatitis B immune globulin.

SOURCE: Adapted from Mast et al., 2005, 2006.

from the 2007 National Immunization Survey, which were collected after

implementation of the 2005 ACIP recommendation, CDC estimates that

the national newborn hepatitis B vaccine coverage was 46% at the age of

1 day (CDC, 2009b).

As noted above, despite the ACIP recommendation to vaccinate all

newborns, about 1,000 newborns each year become chronically infected

with HBV. Even with the ACIP recommendation, birth doses of the hepati-

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IMMUNIZATION 113

BOX 4-1

Summary of ACIP Hepatitis B Vaccination Recommendations

Vaccination of infants

At birth

• Infants born to mothers who are HbsAg-positive should receive hepa-

titis B vaccine and HBIG within 12 hours of birth.

• Infants born to mothers whose HBsAg status is unknown should re-

ceive hepatitis B vaccine within 12 hours of birth. The mother should

have blood drawn as soon as possible to determine her HBsAg status;

if she is HbsAg-positive, the infant should receive HBIG as soon as

possible (no later than the age of 1 week).

• Full-term infants who are medically stable, weigh over 2,000 g, and

are born to HBsAg-negative mothers should receive single-antigen

hepatitis B vaccine before hospital discharge.

• Preterm infants weighing less than 2,000 g and born to HbsAg-

negative mothers should receive the ﬁrst dose of vaccine 1 month

after birth or at hospital discharge.

After the birth dose

• All infants should complete the hepatitis B vaccine series with either

single-antigen vaccine or combination vaccine according to a recom-

mended vaccination schedule.

• Infants born to HBsAg-positive mothers should be tested for HBsAg

and antibody to HBsAg after completion of the hepatitis B vaccine

series at the age of 9–18 months.

Vaccination of children and adolescents

• All unvaccinated children and adolescents less than 19 years old

should receive the hepatitis B vaccine series.

Vaccination of adults

Persons at risk for infection by sexual exposure

• Sex partners of HbsAg-positive persons.

• Sexually active persons who are not in a long-term, mutually mo-

nogamous relationship (for example, persons with more than one sex

partner during the previous 6 months).

• Persons seeking evaluation or treatment for a sexually transmitted

disease.

• Men who have sex with men.

Persons at risk for infection by percutaneous or mucosal exposure to

blood

• Current or recent injection-drug users.

• Household contacts of HBsAg-positive persons.

• Residents and staff of facilities for developmentally disabled

persons.

• Health-care and public-safety workers who have a reasonably antici-

pated risk of exposure to blood or blood-contaminated body ﬂuids.

• Persons with end-stage renal disease, including predialysis, hemodi-

alysis, peritoneal-dialysis, and home-dialysis patients.

• Incarcerated persons.

Others

• International travelers to regions that have high or intermediate levels

(HBsAg prevalence of at least 2%) of endemic HBV infection.

• Persons who have chronic liver disease.

• Persons who have HIV infection.

• All other persons who are seeking protection from HBV infection.

Abbreviations: ACIP, Advisory Committee on Immunization Practices; HBsAg, hepatitis B

surface antigen; HBIG, hepatitis B immune globulin.

SOURCE: Adapted from Mast et al., 2005, 2006.

tis B vaccine are being missed or delayed, which the committee believes is

due to the lack of a delivery-room policy for hepatitis B vaccination. Miss-

ing or delaying the birth dose for infants born to HBsAg-positive women

substantially increases the risk that they will develop chronic hepatitis B.

To reduce the incidence of perinatal HBV infections, the committee offers

the following recommendation:

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114 HEPATITIS AND LIVER CANCER

TABLE 4-1 Hepatitis B Vaccine Schedules for Newborns, by Maternal

HBsAg Status—ACIP Recommendations

Maternal

HbsAg Status

Single-Antigen (Stand-alone)

Vaccine

Single Antigen (Stand-alone) +

Combination Vaccine

Dose Age Dose Age

Positive

Birth (up to 12 hours) 1

Birth (up to 12 hours)

HBIG

Birth (up to 12 hours) HBIG Birth (up to 12 hours)

2 1–2 months 2 2 months

6 months 3 4 months

6 months (Pediarix)

or 12–15 months

(Comvax)

Unknown

Birth (up to 12 hours) 1

Birth (up to 12 hours)

2 1–2 months 2 2 months

6 months 3 4 months

6 months (Pediarix)

or 12–15 months

(Comvax)

Negative 1

a,e

Birth (before

discharge)

a,e

Birth (before

discharge)

2 1–2 months 2 2 months

6–18 months 3 4 months

6 months (Pediarix)

or 12–15 months

(Comvax)

Recombivax HB or Engerix-B should be used for the birth dose. Comvax and Pediarix

cannot be administered at birth or before the age of 6 weeks.

HBIG (0.5 mL) administered intramuscularly in a separate site from vaccine.

Final dose in vaccine series should not be administered before the age of 24 weeks.

Mothers should have blood drawn and tested for HBsAg as soon as possible after admis-

sion for delivery; if mother is found to be HbsAg-positive, infant should receive HBIG as soon

as possible but no later than the age of 7 days.

On a case-by-case basis and only in rare circumstances, ﬁrst dose may be delayed until after

hospital discharge for an infant who weighs ≤2,000 g and whose mother is HbsAg-negative,

but only if physician’s order to withhold birth dose and copy of mother’s original HBsAg-

negative laboratory report are documented in infant’s medical record.

Abbreviations: HBsAg, hepatitis B surface antigen; ACIP, Advisory Committee on Immuniza-ACIP, Advisory Committee on Immuniza-

tion Practices; HBIG, hepatitis B immune globulin. HBIG, hepatitis B immune globulin.

SOURCE: Mast et al., 2005.

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IMMUNIZATION 115

Recommendation 4-1. All infants weighing at least 2,000 grams and

born to hepatitis B surface antigen-positive women should receive

single-antigen hepatitis B vaccine and hepatitis B immune globulin in

the delivery room as soon as they are stable and washed. The recom-

mendations of the Advisory Committee on Immunization Practices

should remain in effect for all other infants.

Administration of prophylaxis in the delivery room is not novel. In

the United States, vitamin K prophylaxis for vitamin K–deﬁciency bleeding

and tetracycline or erythromycin for prophylaxis of neonatal gonococcal

infections are routinely given to infants in the delivery room (American

Academy of Pediatrics, 1961, 1980; Workowski and Berman, 2006). The

World Health Organization recommends that the birth dose of the hepatitis

B vaccine be administered as soon after birth as possible (WHO, 2006).

A pilot project in The Lao People’s Democratic Republic demonstrated

almost 100% coverage when the hepatitis B vaccine was administered in

TABLE 4-2 Hepatitis B Immunization Management of Preterm Infants

Who Weigh Less Than 2,000 g, by Maternal HBsAg Status—ACIP

Recommendations

Maternal

HBsAg Status Recommendation

Positive HBIG + hepatitis B vaccine (within 12 hours of birth)

Continue vaccine series beginning at age of 1–2 months according

to recommended schedule for infants born to HBsAg-positive

mothers (see Table 4-1)

Do not count birth dose as part of vaccine series

Test for HBsAg and antibody to HBsAg after completion of vaccine

series at age of 9–18 months (that is, next well-child visit)

Unknown HBIG + hepatitis B vaccine (within 12 hours of birth)

Test mother for HBsAg

Continue vaccine series beginning at age of 1–2 months according

to recommended schedule based on mother’s HBsAg result (see

Table 4-1)

Do not count birth dose as part of vaccine series

Negative Delay ﬁrst dose of hepatitis B vaccine until age of 1 month or

hospital discharge

Complete vaccine series (see Table 4-1)

Abbreviations: ACIP, Advisory Committee on Immunization Practices; HBIG, hepatitis B im-

mune globulin; HBsAg, hepatitis B surface antigen.

SOURCE: Mast et al., 2005.

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116 HEPATITIS AND LIVER CANCER

the delivery room (WHO, 2006). When mothers were asked to take their

newborns to a vaccination room for their hepatitis B vaccine birth dose,

vaccine coverage was low.

Childhood Vaccination

ACIP recommends that unvaccinated children and adults under 19

years old be given the hepatitis B vaccine series (Mast et al., 2005). Stud-

ies have found racial and ethnic disparities in childhood vaccination rates:

Asian and Paciﬁc Islander (API), Hispanic, and black children had lower

vaccination rates than non-Hispanic white children (CDC, 2000; Darling

et al., 2005; Jenkins et al., 2000; Morita et al., 2008; Szilagyi et al., 2002).

However, when poverty was controlled for, the estimates did not remain sig-

niﬁcantly lower for any racial or ethnic population than for non-Hispanic

white children (CDC, 2009c).

Studies have also found geographic variability in vaccination cover-

age (Darling et al., 2005; Morita et al., 2008; Szilagyi et al., 2002). The

disparities are seen state by state and within regions. For instance, in 2008,

Maryland had the highest percentage of children who were up to date

their vaccinations with a rate of 82.3%, compared with Montana with a

rate of 59.2% (CDC, 2009c). Szilagyi et al. (2002) looked at the use of

reminder and recall interventions by primary-care providers to increase

immunization rates for children under 2 years old. Before the intervention,

the baseline geographic disparity was an 18% difference between inner-

city children (55%) and suburban children (73%). Within 3 years of the

establishment of the intervention, the vaccination rates had increased in all

areas, including 84% in the inner city and 88% in the suburbs.

All but three states—Alabama, Montana, and South Dakota—have

a childhood hepatitis B vaccination mandate for daycare or school en-

try (Immunization Action Coalition, 2009). A retrospective cohort study

of Chicago public-school children found that the hepatitis B vaccination

school-entry mandate led to an increase in the vaccination rate among all

children and substantially decreased the disparity in the vaccination rate

between white children and black and Hispanic children (Morita et al.,

2008). Before the school-entry mandate, the study found immunizations

rates in non-Hispanic white, black, and Hispanic children of 89%, 76%,

and 74%, respectively. After the mandate was enacted, the rates changed to

The immunization series used in these data includes the following vaccinations—4 or more

doses of DTaP, 3 or more doses of poliovirus vaccine, 1 or more dose of any measles-contain-

ing vaccine, 3 or more doses of Hib vaccine, 3 or more doses of hepatitis B vaccine, as well

as 1 or more dose of varicella vaccine (CDC, 2009c).

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IMMUNIZATION 117

88%, 81%, and 87%, respectively. Although a disparity in the vaccinations

rates persisted, the gap was narrowed (Szilagyi et al., 2002).

Other studies also have found that school-entry mandates are effec-

tive in increasing hepatitis B vaccination rates (CDC, 2001b; Koff, 2000;

Olshen et al., 2007; Zimet et al., 2008) although such mandates may

not be as effective in children in daycare (Stanwyck et al., 2004). CDC

(2007) found that about 75% of states reported at least 95% hepatitis B

vaccination coverage of children in kindergarten in 2006–2007. Another

study reported that hepatitis B vaccine series coverage for children 19–35

months old in 2000–2002 ranged from 49% to 82%, depending on the

state (Luman et al., 2005).

Special attention needs to be given to vaccination coverage of foreign-

born children from countries that have a high prevalence of hepatitis B;

because of their high risk of prior infection, laboratory testing is indicated

to determine HBV-infection status.

Recommendation 4-2. All states should mandate that the hepatitis B

vaccine series be completed or in progress as a requirement for school

attendance.

Parents of foreign-born children from HBV-endemic countries should

be given information about testing for HBV and should have their children

tested before vaccination.

Adult Vaccination

Hepatitis B vaccination for adults is recommended to high-risk

populations—people at risk for HBV infection from infected household

contacts and sex partners, from occupational exposure to infected blood

or body ﬂuids, and from travel to regions with high or intermediate levels

of endemic HBV infection (Mast et al., 2006). The estimated chance that

an acute HBV infection will become chronic decreases with increasing age

(see Table 4-3). The probability that an acute HBV infection in a 1-year-old

will become chronic is 88.5%, but only 9.0% in a 19-year-old (Edmunds et

al., 1993). Universal hepatitis B vaccination for adults is not recommended

(that is, people born before 1991 do not need to receive the hepatitis B vac-

cine unless they are at risk for HBV infection). It is not cost-effective; that

is, the health beneﬁts achieved do not justify the cost compared with other

potential health-care interventions (Gold et al., 1996). Interventions in the

United States that cost less than $100,000 per quality adjusted life year

(QALY) gained are generally considered to be cost-effective (Owens, 1998;

WHO, 2009). Universal hepatitis B vaccination is not cost-effective even in

adult Asians and Paciﬁc Islanders, who have a higher prevalence of HBV

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118 HEPATITIS AND LIVER CANCER

infection than the general US population (Hutton et al., 2007). However,

ring vaccination—vaccination of the close contacts of people found to be

chronically infected with HBV—is cost-effective (Hutton et al., 2007).

Figure 4-1 shows estimated cost effectiveness of hepatitis B vaccination

for different age groups and different incidences of acute hepatitis B. The

leftmost line of the graph represents a recent estimate of acute HBV inci-

dence in the general US population (Hutton et al., 2007). This estimate is

expressed as the annual percentage of people in the population who acquire

acute HBV infection. At that incidence, hepatitis B vaccination of adults

in the general US population costs more than $100,000 per QALY gained,

and is not considered to be cost-effective.

In 2004, just over half (54.6%) the adults at high risk for HBV infection

had received the hepatitis B vaccine, including about 75% of health-care

workers and 64% of public-safety workers for whom vaccination is recom-

mended (CDC, 2006; Simard et al., 2007). Of adults with acute hepatitis

B, 61% reported having missed an opportunity for vaccination (Williams

et al., 2005). Low coverage of high-risk adults is attributed to the lack of

dedicated vaccine programs, limited vaccine supply, inadequate funding,

and noncompliance by the involved populations (Mast et al., 2006).

TABLE 4-3 Estimated Chance That an Acute Hepatitis B

Infection Becomes Chronic with Age

Age (years)

Estimated Chance That Acute HBV Infection

Becomes Chronic (%)

1 88.5

2 52.5

3 41.3

4 34.6

5 29.8

6 26.1

7 23.3

8 20.9

9 19.0

10 17.3

11 15.9

12 14.7

13 13.6

14 13.0

15 11.7

16 11.0

17 10.3

18 9.6

19 9.0

NOTE: Calculated using a formula from Edmunds et al., 1993.

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IMMUNIZATION 119

0.0050%

0.0150%

0.0250%

0.0350%

0.0450%

0.0550%

0.0650%

0.0750%

Annual Incidence of Acute HBV Infection

Age of Person

Vaccinated

$150,000-$200,000

$100,000-$150,000

$50,000-$100,000

$0-$50,000

>$200,000

Cost per QALY Gained

Figure 4-1, editable

FIGURE 4-1 Estimated cost of adult hepatitis B vaccination per quality adjusted life

year (QALY) gained for different age groups and different rates of acute hepatitis

B virus (HBV) infection incidence. Incidence is expressed as the annual percentage

of the population becoming acutely infected with HBV (for example, incidence of

0.005% means that 5 persons per 100,000 are acutely infected with HBV each year,

and incidence of 0.075% means that 75 persons per 100,000 are acutely infected

with HBV each year). Shadings show different levels of cost per QALY gained. In-

terventions are more cost-effective as one moves down (lower age) and to the right

(higher incidence). Interventions that cost less than approximately $100,000 per

QALY gained are generally considered cost-effective in the United States (Owens,

1998; WHO, 2009). The leftmost line, incidence of 0.0050%, is based on a recent

estimate of acute hepatitis B incidence in the general US population (Hutton et al.,

2007). Analysis performed by D. Hutton using the model developed in Hutton et

al., 2007.

Adults at Risk from Sexual Exposure In a national sample of 500 sexually-

transmitted-disease (STD) clinics, the percentage that offered the hepatitis

B vaccine increased from 25% to 45% (p = 0.02) from 1997 to 2001, and

the percentage of the clinics that considered all patients eligible for the vac-

cine rose from 9% to 26% (p = 0.023) during the same period (Gilbert et

al., 2005). However, declining hepatitis B vaccination rates were reported

in a study of six STD clinics in the United States (Harris et al., 2007). The

researchers collected data on patient visits and hepatitis B vaccinations for

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120 HEPATITIS AND LIVER CANCER

the period 1997–2005 and found that vaccination rates declined during the

later years. Possible reasons for the decline include ﬁscal constraints and

increasing rates of prior vaccination.

Several studies have reported that when STD clinics offered the hepa-

titis B vaccine, many patients at high risk for HBV infection opted to be

vaccinated. A study of 194 STD clinic patients found that 62% had not

previously been vaccinated for hepatitis B, and 50% of the 62% elected to

receive the vaccination (Samoff et al., 2004). A national program to vacci-

nate adults at STD clinics for hepatitis B is likely to be cost saving to society

(Miriti et al., 2008). In an anonymous HIV-testing program in Madison,

WI, 86% of patients were considered to be at high risk for HBV infection;

51% of the 86% initiated hepatitis B vaccination, and 80% who initiated

vaccination completed the vaccine series (Savage et al., 2000).

Foreign-born people from HBV-endemic countries who reside in the

United States are at risk for HBV infection from sexual exposures. Con-

tinuing sexual transmission of HBV in these communities is likely. Thus,

foreign-born adults may be at high risk for acquiring hepatitis B, and

women may transmit the virus to their newborns. Foreign-born adults

would beneﬁt from laboratory testing to determine their infection status

and subsequent hepatitis B vaccination of susceptible people.

Adults at Risk from Injection-Drug Use CDC estimates that injection-

drug users (IDUs) account for 15% of acute HBV infections in the United

States (Daniels et al., 2009). The incidence of HBV infection in susceptible

IDUs ranges from 10 to 30 per 100 person-years (Des Jarlais et al., 2003;

Hagan et al., 1999). Hepatitis B vaccine coverage rates in IDUs are low and

estimated to be 3–20% (Altice et al., 2005; Kuo et al., 2004; Lum et al.,

2008) (see Table 4-4). The highest reported vaccination rate in US IDUs

was 22%, in new injectors studied in 2000–2002 (Lum et al., 2003). In a

study conducted in San Francisco, only 13% of IDUs over 30 years old had

ever been offered hepatitis B vaccination compared with 25% of younger

injectors (Seal et al., 2000).

On-site hepatitis B vaccination achieves higher success rates in IDUs

than referral to other locations (summarized in Table 4-4). In a multisite

study of IDUs in ﬁve US cities, IDUs participating in a randomized clinical

trial to reduce HIV and HCV transmission were offered hepatitis B vaccina-

tion under a variety of conditions. Vaccine uptake was highest when it was

provided on site and during the initial study visit (Campbell et al., 2007).

A New Haven mobile health van at a needle-exchange program found that

66% of those initially offered the hepatitis B vaccine completed all three

doses (Altice et al., 2005). Des Jarlais et al. (2001) reported a 31% comple-

tion rate in Alaskan IDUs given an off-site referral compared with 83% in

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IMMUNIZATION 121

IDUs offered on-site vaccination and a $5–10 incentive at a New York City

needle-exchange program.

The committee believes that the hepatitis B vaccination rate in the

high-risk IDU population is unacceptably low. Studies of vaccine protocols

show that completion rates are substantially higher when vaccination is

offered at such a location as a needle-exchange program. Using a modeling

approach, Hu et al. (2008) found that hepatitis B vaccination of IDUs who

participate in needle-exchange programs in the United States is likely to be

cost-saving to society.

Incarcerated Populations Hennessey et al. (2009) reported that only 12%(2009) reported that only 12%

of inmates at three jails in Chicago, Detroit, and San Francisco had sero-

logic evidence of hepatitis B vaccination compared with a 25% self-reported

vaccination rate in the US population. The study also found an unexpect-

edly high rate of chronic hepatitis B infections (3.6%) and the lowest rate

of hepatitis B vaccination (10%) among Hispanic inmates.

Twenty states require that inmates receive at least some immunizations,

including the hepatitis B vaccine (CDC, 2008a). Four of those states require

vaccination of all inmates, and 16 require only that juvenile inmates be

vaccinated. Several studies reported that if offered the hepatitis B vaccine,

most inmates (60–93%) would agree to be vaccinated (Rotily et al., 1997;

Vallabhaneni et al., 2004). Alternative vaccination schedules may be effec-

tive for inmates. In a study of inmates in Denmark, 63% completed the

hepatitis B vaccination series on an accelerated 3-week schedule compared

with 20% of those on a 6-month schedule (Christensen et al., 2004).

According to CDC, 28.8% of patients who had acute hepatitis B re-

ported a history of incarceration before HBV infection (Goldstein et al.,

2002). Thus, immunization of incarcerated people could potentially prevent

nearly one-third of all acute hepatitis B cases in the United States. Although

most prison systems in the United States do not provide universal hepatitis

B vaccination for inmates, Charuvastra et al. (2001) noted that 25 of 26

states that responded to a survey reported that they would routinely vac-

cinate their inmates against HBV infection if funding for vaccination were

available.

Although the length of stay is shorter in jails than in prisons, offering

hepatitis B vaccination to jail inmates is feasible and provides a beneﬁt to

the community after the inmates are released. Using an accelerated schedule

increases the completion rate (Christensen et al., 2004). Substantial protec-

tion is provided after even one or two of the three doses of the series. It is

important to have a health-record system that tracks immunizations so that

the vaccine series can be continued if later incarcerations occur. Ideally, im-

munizations administered in jails will be captured in an adult immunization

registry (see discussion on immunization-information systems below) so

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122 HEPATITIS AND LIVER CANCER

TABLE 4-4 Studies of Hepatitis B Vaccination Rates in Injection-Drug

Users

Reference Location Sample; Design

Percentage Previously

Vaccinated

Percentage Ever Offered

Vaccination

Percentage Completed

Vaccination Series

Cross-sectional studies of vaccination rates

Seal et al., 2000 San Francisco, CA 135 under 30 years old, 96 at

least 30 years old

Cross-sectional

25% under 30 years old,

13% at least 30 years old

Lum et al., 2008 San Francisco, CA 831 young IDUs

Cross-sectional

22%; 18% among HCV

positive

Kuo et al., 2004 Baltimore, MD 324 IDUs, NIDUs

Cross-sectional

10% IDUs; 14% NIDUs

Additional vaccination studies

Campbell et al., 2007 5 US cities 3,181

Cohort; vaccination protocol

varied by city

Vaccination highest where

available on site (83% had at

least one dose); incentives did

not affect vaccination rates

Altice et al., 2005 New Haven, CT; mobile

health van at SEP

134 HBV-negative IDUs

Observational

3% 94% had one dose; 77% had

two doses; 66% had three

doses

Des Jarlais et al., 2001 Anchorage, AK;

New York City

AK cohort referred to clinic

(350); New York City cohort

offered on-site vaccination

at SEP (36) + small cash

incentives

Cohort

30/36 (83%) offered on site

had all three doses vs 31% of

those referred to clinic

Hutchinson et al., 2004 Glasgow, Scotland, prison

vaccination, community

assessment

In 1999, offered HBV

vaccination to all inmates;

surveyed new injectors (within

5 years)

1993, 16%

1994, 19%

1999, 15%

2002, 52%

(56% received hepatitis B

vaccine while in prison)

Abbreviations: HBV, hepatitis B virus; IDU, injection-drug user; NIDU, non-injection-drug

user; SEP, syringe-exchange program.

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IMMUNIZATION 123

TABLE 4-4 Studies of Hepatitis B Vaccination Rates in Injection-Drug

Users

Reference Location Sample; Design

Percentage Previously

Vaccinated

Percentage Ever Offered

Vaccination

Percentage Completed

Vaccination Series

Cross-sectional studies of vaccination rates

Seal et al., 2000 San Francisco, CA 135 under 30 years old, 96 at

least 30 years old

Cross-sectional

25% under 30 years old,

13% at least 30 years old

Lum et al., 2008 San Francisco, CA 831 young IDUs

Cross-sectional

22%; 18% among HCV

positive

Kuo et al., 2004 Baltimore, MD 324 IDUs, NIDUs

Cross-sectional

10% IDUs; 14% NIDUs

Additional vaccination studies

Campbell et al., 2007 5 US cities 3,181

Cohort; vaccination protocol

varied by city

Vaccination highest where

available on site (83% had at

least one dose); incentives did

not affect vaccination rates

Altice et al., 2005 New Haven, CT; mobile

health van at SEP

134 HBV-negative IDUs

Observational

3% 94% had one dose; 77% had

two doses; 66% had three

doses

Des Jarlais et al., 2001 Anchorage, AK;

New York City

AK cohort referred to clinic

(350); New York City cohort

offered on-site vaccination

at SEP (36) + small cash

incentives

Cohort

30/36 (83%) offered on site

had all three doses vs 31% of

those referred to clinic

Hutchinson et al., 2004 Glasgow, Scotland, prison

vaccination, community

assessment

In 1999, offered HBV

vaccination to all inmates;

surveyed new injectors (within

5 years)

1993, 16%

1994, 19%

1999, 15%

2002, 52%

(56% received hepatitis B

vaccine while in prison)

Abbreviations: HBV, hepatitis B virus; IDU, injection-drug user; NIDU, non-injection-drug

user; SEP, syringe-exchange program.

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124 HEPATITIS AND LIVER CANCER

that the vaccine series can be completed at other sites, such as drug-treat-

ment centers and STD clinics.

Hepatitis B vaccination of inmates costs the correctional system $415

per HBV infection averted, but it provides additional postincarceration

savings to society as a whole (Pisu et al., 2002).

Other At-Risk Adults

HIV-infected people. At a clinic that serves primarily HIV-infected pa-

tients in Jacksonville, FL, 45% of 1,576 HIV-infected patients were consid-

ered to be at risk for HBV infection (Bailey et al., 2008), and 30% of those

at risk were not offered hepatitis B vaccine by their health-care providers.

Routine hepatitis B vaccination at HIV clinics is highly cost-effective, with

a cost of $4,400 per QALY gained (Kim et al., 2006). Similarly, hepatitis B

vaccination at STD testing, counseling, and treatment sites has been dem-

onstrated to be highly cost-effective (Miriti et al., 2008).

Institutionalized populations. Vellinga et al. (1999) reviewed the litera-

ture and reported that among institutionalized developmentally disabled

people in the United States, the prevalence of anti-HBs antibody ranged

from 36% to 63% in residents who had Down syndrome and from 48%

to 69% in people who had other intellectual disabilities. HBsAg prevalence

was very high—27–51% in people who had Down syndrome and 6–9% in

people who had other intellectual disabilities—and this suggests that many

residents of institutions are immunized by natural infection rather than by

vaccination. The committee did not ﬁnd data on rates of hepatitis B vac-

cination of institutionalized developmentally disabled people. Because they

are at risk for hepatitis B, they would beneﬁt from vaccination.

Occupational exposure to hepatitis B virus. Only 75% of health-care

workers (HCWs) in the United States—a population at high risk for HBV

infection—have received the three-dose vaccine series in 2002-2003 (Simard

et al., 2007). The vaccination rate was highest in physicians and nurses

(81%) and lowest among black HCWs (67.6%).

Identifying At-Risk Adults

As discussed above, recommendations regarding childhood hepatitis B

vaccination are aimed at achieving universal coverage, and recommenda-

tions regarding adult vaccination focus on the identiﬁcation of risk popula-

tions for targeted immunization efforts. The identiﬁcation of at-risk adults

has proved problematic (CDC, 2006), and current CDC recommendations

have emphasized both site-based and individual-based risk assessment to

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IMMUNIZATION 125

improve hepatitis B vaccine coverage (Mast et al., 2006). A key to the suc-

cess of such an approach is the routine availability of hepatitis B vaccine in

settings where a high proportion of persons who have risk factors are seen

(such as STD clinics), in primary-care and specialty-care medical settings,

and in occupational-health programs.

Identiﬁcation of at-risk people is particularly challenging in medical

settings in that risks must be assessed in individual patients. In many

health-care settings, physicians and other providers might not be comfort-

able in asking direct questions to elicit risk history with respect to sexual or

percutaneous exposures (Ashton et al., 2002; Bull et al., 1999; Maheux et

al., 1995). Time constraints during medical appointments and inadequate

provider education in the assessment of risk histories also might lead to

insufﬁcient assessment of risk history. In addition, there may be discrepan-

cies between a patient’s self-assessment of risk and a health-care provider’s

documented assessment (Fishbein et al., 2006). Therefore, the ACIP recom-

mends that hepatitis B vaccination be offered to any adult who requests it,

regardless of a provider’s assessment of risk (Mast et al., 2006).

Recommendation

In 2007, there were more than 40,000 new acute HBV infections in

adults (Daniels et al., 2009). To reduce the incidence of HBV infection in

adults, the committee offers the following recommendation:

Recommendation 4-3. Additional federal and state resources should be

devoted to increasing hepatitis B vaccination of at-risk adults.

• Correctional institutions should offer hepatitis B vaccination to all

incarcerated persons. Accelerated schedules for vaccine administra-

tion should be considered for jail inmates.

• Organizations that serve high-risk people should offer the hepatitis

B vaccination series.

• Efforts should be made to improve identiﬁcation of at-risk adults.

Health-care providers should routinely seek risk histories from

adult patients through direct questioning and self-assessment.

• Efforts should be made to increase rates of completion of the vac-

cine series in adults.

• Federal and state agencies should determine gaps in hepatitis B

vaccine coverage among at-risk adults annually and estimate the

resources needed to ﬁll the gaps.

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126 HEPATITIS AND LIVER CANCER

Immunization-Information Systems

Immunization registries are databases that allow the collection and

consolidation of vaccination data from multiple health-care providers.

They also make it possible to generate reminder and recall notiﬁcations

and assess vaccination coverage in deﬁned geographic areas. Immunization-

information systems (IISs) are registries that have additional capabilities,

such as vaccine management, adverse-event reporting, lifespan vaccination

histories, and linkages with electronic data (CDC, 2005). According to a

report of the National Vaccine Advisory Committee (NVAC), IISs have been

demonstrated to improve immunization coverage, support vaccine safety,

increase timeliness of immunization, and help in the study of immuniza-

tion effectiveness in children (Hinman et al., 2007). IISs can also prevent

unnecessary immunizations by giving providers a single source for patients’

immunization histories (Yawn et al., 1998), reduce “no-show” rates, reduce

vaccine waste, save staff costs by avoiding manual review of multiple re-

cords, aid in the establishment of Healthcare Effectiveness Data and Infor-

mation Set (HEDIS) performance measures, and avoid costs associated with

the National Immunization Survey (NIS) (Bartlett et al., 2007).

The development of IISs began in 1993 when CDC started to award

planning grants to develop registries in every state (CDC, 2001a). President

Clinton established the national Childhood Immunization Initiative by

directing the secretary of health and human services to work with states

to build “an integrated immunization registry system.” That initiative led

to the Initiative on Immunization Registries, which was spearheaded by

the NVAC with support from CDC’s National Immunization Program and

the Department of Health and Human Services National Vaccine Program

Ofﬁce (Bartlett et al., 2007). Since 1994, CDC’s National Center for Im-

munization and Respiratory Diseases (formerly the National Immunization

Program) has provided funding to 64 grantees (all 50 states, 6 cities, and

the US territories) through Section 317 of the Public Health Service Act for

the development of IISs. From 1994 through 2001, $181.3 million was al-

located by CDC, and an additional $20 million was provided by the Robert

Wood Johnson Foundation (CDC, 2001a). Only one state had reported no

efforts to develop and implement an IIS as of December 31, 2005 (Hinman

et al., 2007). However, three other states did not report to CDC in 2005

the percentage of children younger than 6 years old who participated in an

IIS, and this might indicate inadequacy of IISs in those states.

CDC has indicated a commitment to support the continued develop-

ment and expansion of state and community IISs (CDC, 2008b) and has a

goal of including more than 95% of children under 6 years old in grantee

IISs by 2010. To address wide variation in the performance of IISs na-

tionally, CDC required detailed business plans from grantees in 2006 to

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IMMUNIZATION 127

describe operational and ﬁnancial objectives of the systems. In addition, a

technical work group was established to develop approaches to measuring

performance of the systems against 12 functional standards (Hinman et al.,

2007). There are also plans to develop an IIS certiﬁcation process.

As the state and community IISs develop, they are increasingly used for

broader purposes, such as emergency preparedness and response (Boom et

al., 2007), monitoring the impact of vaccine shortages (Allred et al., 2006),

and monitoring the use of new vaccines. There have also been calls to

integrate IISs with other child-information systems—such as vital registra-

tion, newborn dried-blood spot screening, and early hearing detection and

intervention (Saarlas et al., 2004)—and to expand the systems to include

adolescents and adults. The NVAC reported that as of 2005, 87% of CDC

grantees included adolescents in their IISs, and 75% included information

on persons 50 years old and older (Hinman et al., 2007).

In 2009, the NVAC issued new recommendations for federal adult im-

munization programs (HHS, 2009).One recommendation was that CDC

and the Health Resources and Services Administration (HRSA) devote

resources to the inclusion of adult immunization records in all grantee

IISs, and another was that all grantees be required to implement adult im-

munization activities and adopt ACIP recommendations for routine adult

immunization.

Recommendation 4-4. States should be encouraged to expand

immunization-information systems to include adolescents and adults.

• Systems should allow the sharing of information between states so

that immunization status can be tracked when people move from

state to state.

• Vaccine registries should include adult populations, such as incar-

cerated persons, IDUs, and people who have STDs.

• Data sharing on vaccination status should be established between

correctional facilities and public-health departments.

Barriers to Hepatitis B Vaccination

Mistrust of Vaccination

Like other childhood vaccinations, hepatitis B vaccination is some-

times refused because patients or parents of children have concerns about

the safety of a vaccine (Allred et al., 2005; Gust et al., 2008; Smith et al.,

2006a). The committee is unaware of credible evidence of serious harms

caused by the hepatitis B vaccine in its many forms. In a 2002 scientiﬁc

review by the Institute of Medicine, the hepatitis B vaccine was not found

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128 HEPATITIS AND LIVER CANCER

to be associated with adverse health outcomes (IOM, 2002). The commit-

tee believes that it is one of the safest vaccines available. The efforts of

groups opposed to vaccination present a serious obstacle to comprehensive

vaccination coverage, which is essential for the prevention and control of

hepatitis B in the United States.

Payment for Vaccines

Insurance Coverage

Health-insurance coverage for the nonelderly population (less than

65 years old) is provided by employers (63%) and public programs (11%

by the Medicaid/Children’s Health Insurance Program and 2% by other

public programs) or is acquired by individuals in the private market (5%)

(Holahan and Cook, 2008). Some 17% of Americans under 65 years old

were reported as chronically uninsured in 2007, but as many as one-third

of Americans were uninsured for at least some of the time in 2007–2008

(Families USA, 2009b). Robust coverage for vaccinations, including hepa-

titis B vaccination, is provided by public insurance plans (Table 4-5). Pri-

vate insurance plans have variable coverage for vaccinations and various

degrees of cost-sharing. Insurance coverage for vaccinations also varies

substantially with age: children under 5 years old and people 65 years old

and over have high rates of private or public coverage (89% and nearly

100%, respectively). People 18–64 years old have much lower rates (50%)

because of lack of insurance, inadequate insurance, and the absence of a

public safety net for recommended adult vaccinations (IOM, 2003).

Insurance coverage has been demonstrated to have an important impact

on access to preventive and other health services and on health outcomes

(IOM, 2009). Studies in children involving various vaccine series, including

hepatitis B vaccine, and in adults transitioning to Medicare have shown

notable increases in vaccination rates in those with insurance coverage

(IOM, 2009). In an NIS sample of children 19–24 months old, recom-

mended vaccination completion rates were found in 76% of the children

covered by private insurance, 70% of the children covered by Medicaid or

the Children’s Health Insurance Program (CHIP), and 53% of uninsured

children (Smith et al., 2006b).

Public Vaccine Programs and Insurance

Vaccines for Children program. Children with no private insurance

may be covered up to the age of 18 years by the Vaccines for Children

(VFC) program administered by CDC (CDC, 2003). The VFC program

was created by the Omnibus Budget Reconciliation Act of 1993 as a new

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IMMUNIZATION 129

entitlement program to be a required part of each state’s Medicaid plan.

The program began in October 1994. The Ofﬁce of Management and

Budget approves funding for the VFC program. Funding is through the

Centers for Medicare and Medicaid Services to CDC, and awards are made

to eligible grantees. The VFC program provides a vaccination entitlement

for Medicaid-eligible, uninsured, American Indian and Alaska Native, and

underinsured children who receive vaccines at federally qualiﬁed health

centers (FQHCs). The VFC program negotiates vaccine prices at the federal

level and allocates credits to states to distribute vaccines free of charge. The

program does not cover any of the practice-based costs associated with the

administration of the vaccines. Payment for vaccine administration is gen-

erally sought from speciﬁc insurance programs, such as Medicaid, or from

parents of VFC-eligible, non-Medicaid children (CDC, 2003).

Section 317 Immunization Grant program. The Section 317 Immuni-

zation Grant Program is a federal discretionary grants program for states

and other US jurisdictions (CDC, 2009d). It was established by the 1962

Vaccination Assistance Act and was the primary source of federal funds

for vaccine purchase until it was supplanted by the VFC program in 1993.

Unlike the VFC program, Section 317 provides federal funds for both vac-

cine purchase and vaccine-related infrastructure, such as population needs

assessments, surveillance, compliance monitoring, training, and school-

based delivery systems. The program targets immunization coverage for

underinsured children and youths not eligible for the VFC program and to

a small degree uninsured and underinsured adults. In 2007, CDC created

the Adult Hepatitis B Vaccine Initiative by using savings from Section 317

funds to provide free vaccine for high-risk adults in various community

settings. Funding for vaccine costs totaled $36 million in the ﬁrst 2 years;

this resulted in the delivery of over 581,000 doses, 343,000 of which re-

portedly were administered. The initiative involves 56 grantees that enroll

2,437 sites, of which 38% are local health departments, 20% STD clinics,

13% primary-care loci, 11% jails or prisons, and 18% other sites, includ-

ing substance-abuse and HIV centers (personal communication, J. Ward,

CDC, July 30, 2009). However, Section 317 funding for adult vaccination

initiatives does not support the infrastructure and medical-supply costs to

deliver vaccines to people at highest risk.

Children’s Health Insurance Program. The federal CHIP was estab-

lished in 1997 under Title IX of the Social Security Act and was expanded

in the Children’s Health Insurance Program Reauthorization Act of 2009

(CMS, 2009). It is a federal block-grant program that requires state match-

ing funds to expand health-care coverage to children under 18 years old

and pregnant women who do not meet income eligibility requirements for

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130 HEPATITIS AND LIVER CANCER

TABLE 4-5 Public Health-Insurance Plans

Coverage Medical Management Vaccination Target Audience Cost Structure

US Department of Veterans

Affairs

7.9 million beneﬁciaries

Hepatitis B, hepatitis C Dedicated hepatitis program 100% Veterans

No cost-sharing except for

non-service-connected veterans

FEHBP

8 million beneﬁciaries

Hepatitis B, hepatitis C Coverage similar to private

plans

Coverage similar to private

plans

Federal employees Coverage similar to private

plans

MEDICARE Parts A, B,

C, D

49 million beneﬁciaries

Hepatitis B, hepatitis C Yes High-risk group coverage People at least 65 years

old, disabled, people with

end-stage renal disease

Coinsurance or copayment

applies only after yearly

deductible has been met

MEDICAID, EPSDT

43 million beneﬁciaries

Hepatitis B, hepatitis C Yes Yes Low-income people,

families with children,

SSI recipients, pregnant

women

States have option to impose

nominal copayment for

beneﬁciaries on basis of

income

VFC Hepatitis B No Yes Children up to 18 years

old who are uninsured,

Medicaid-eligible,

underinsured, American

Indians, Alaska Natives

Covers cost of vaccines but

not administration; providers

can charge administration

fee for non–Medicaid-eligible

children

SECTION 317

Immunization Program

Hepatitis B No Yes Children, adolescents not

served by VFC program;

small percentage (about

5%) used for adults

Can be used for infrastructure;

annual appropriations vary

CHIP

7.4 million child, 334,000

adult

beneﬁciaries

Hepatitis B Yes Yes Insurance beneﬁts for

children up to 18 years old

(for families making no

more than $44,100/year)

whose income is too high

for Medicaid, too low for

private insurance

Block grant program: federal

match more than Medicaid

match

Household income limitations apply.

Covers children under 6 years old and pregnant women whose family income is no more

than 133% of federal poverty level and children 6–18 years old below 100% of federal poverty

level.

Abbreviations: EPSDT, Early Periodic Screening, Diagnosis, and Treatment program; FEHBP,

Federal Employees Health Beneﬁts Program; VFC, Vaccines for Children; CHIP, Children’s

Health Insurance Program.

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IMMUNIZATION 131

TABLE 4-5 Public Health-Insurance Plans

Coverage Medical Management Vaccination Target Audience Cost Structure

US Department of Veterans

Affairs

7.9 million beneﬁciaries

Hepatitis B, hepatitis C Dedicated hepatitis program 100% Veterans

No cost-sharing except for

non-service-connected veterans

FEHBP

8 million beneﬁciaries

Hepatitis B, hepatitis C Coverage similar to private

plans

Coverage similar to private

plans

Federal employees Coverage similar to private

plans

MEDICARE Parts A, B,

C, D

49 million beneﬁciaries

Hepatitis B, hepatitis C Yes High-risk group coverage People at least 65 years

old, disabled, people with

end-stage renal disease

Coinsurance or copayment

applies only after yearly

deductible has been met

MEDICAID, EPSDT

43 million beneﬁciaries

Hepatitis B, hepatitis C Yes Yes Low-income people,

families with children,

SSI recipients, pregnant

women

States have option to impose

nominal copayment for

beneﬁciaries on basis of

income

VFC Hepatitis B No Yes Children up to 18 years

old who are uninsured,

Medicaid-eligible,

underinsured, American

Indians, Alaska Natives

Covers cost of vaccines but

not administration; providers

can charge administration

fee for non–Medicaid-eligible

children

SECTION 317

Immunization Program

Hepatitis B No Yes Children, adolescents not

served by VFC program;

small percentage (about

5%) used for adults

Can be used for infrastructure;

annual appropriations vary

CHIP

7.4 million child, 334,000

adult

beneﬁciaries

Hepatitis B Yes Yes Insurance beneﬁts for

children up to 18 years old

(for families making no

more than $44,100/year)

whose income is too high

for Medicaid, too low for

private insurance

Block grant program: federal

match more than Medicaid

match

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132 HEPATITIS AND LIVER CANCER

Medicaid but cannot afford private health insurance. CHIP is available to

citizens and some legal immigrants, and states can charge a premium for

coverage and impose cost-sharing based on income. States have the option

of using the grant money to establish independent insurance programs or to

expand eligibility criteria for Medicaid; in the latter case, the coverage must

conform to Medicaid requirements. Currently, 39 states have programs that

are not expansions of Medicaid. Non-Medicaid CHIP programs must pro-

vide coverage for ACIP-recommended immunizations, including hepatitis B,

and must meet a federally established minimal overall coverage.

Public programs for adults. Nonelderly adults have more limited ac-

cess to publicly funded vaccination programs and public insurance beneﬁts

than children. Adults enrolled in Medicaid make up 25% of enrollees and

are provided coverage for vaccinations, but the coverage varies between

states. Most states provide coverage based on ACIP standards, including

hepatitis B immunization. However, cost-sharing is common, and payment

of providers varies from ﬁxed-fee schedules, which allow separate billing

for vaccine administration (Rosenbaum et al., 2003). Elderly adults covered

under Medicare and enrolled in Medicare Part B are covered for hepatitis B

vaccination if they fall into ACIP-designated high-risk or intermediate-risk

populations. The Medicare Part B deductible must be met, and the relevant

copayment or coinsurance is applicable to the hepatitis B coverage (CMS,

2008).

Federal law generally restricts coverage for adults under CHIP to preg-

nant women but does permit coverage of adults without dependent children

under special waivers from the federal government. Eleven states are pro-

viding coverage to low-income adults under such waivers. The 2009 CHIP

reauthorization act will phase out funding for such waivers by 2011 and

thereby eliminate this public source of adult-vaccination coverage (Families

USA, 2009a). Public Health Service Section 317 grants amounted to $527

million in 2008 and allow vaccination coverage for uninsured and under-

insured adults. Nearly all the money, however, was used for vaccinating

children and youths. In 2005, it was reported that less than 5% of Section

317 funding was used for adult-vaccination efforts (Mootrey, 2007).

Private Insurance Plans

Employers provide over 66% of all health insurance for 177 million

Americans under the age of 65 years (U.S. Census Bureau, 2007). Trends in

private health-insurance coverage have reﬂected a shift from comprehensive

coverage with low out-of-pocket costs (health maintenance organizations,

HMOs) to broader access, network-driven, and higher-cost–sharing health

plans (preferred provider organization, PPOs) (Figure 4-2). The latter offer

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IMMUNIZATION 133

free choice of providers and hospitals but require out-of-pocket spending

(deductibles) by the consumer before coverage under the plan, cost-sharing

when the plan does provide coverage (ﬂat dollar copayments or coinsur-

ance payments), and different levels of coverage for the same service when

acquired in-network versus out-of-network. PPO insurance arrangements

now cover more than 58% of all persons who have employment-based

health insurance (Figure 4-2).

Coverage for hepatitis B and other ACIP-recommended vaccinations is

routine in HMOs but variable in PPOs and other private insurance plans.

There is little or no cost-sharing for vaccinations and other preventive ser-

vices in HMOs, whereas it is greater in PPOs and other health plans because

of applicable deductibles and coinsurance or copayments. Cost-sharing is

greatest in health plans that have very high deductibles (high-deductible

health plans, HDHPs). In 2008, 8% of all privately insured Americans

were covered by HDHPs with annual deductibles of $1,000 or more (Kaiser

Family Foundation and HRET, 2008). HDHPs can pose formidable barri-

ers to preventive care and vaccination unless these services are speciﬁcally

exempted from the deductible or enrollees are provided a separate source

of funds to pay for them (for example, a reimbursement arrangement or a

FIGURE 4-2 Trends in private health-insurance coverage.

Abbreviations: PPO, preferred provider organization; POS, point of service; HMO,

health maintenance organization; HDHP, high-deductible health plan.

SOURCES: HIAA, 1988; Kaiser Family Foundation and HRET, 2008; KPMG,

1996.

20%

40%

60%

80%

100%

Indemnity PPO POS HMO HDHP

1988 1993 1996 2002 2007

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134 HEPATITIS AND LIVER CANCER

funded health savings account). To ensure vaccination coverage for children

under private insurance arrangements, most states have mandates for child-

hood immunizations. The regulations may also prohibit cost-sharing in the

form of deductibles or coinsurance for those services (American Academy

of Pediatrics, 2008). State mandates for recommended adult vaccinations

are less common. Employers that use national health plans are exempted

from the state mandates because their health-beneﬁt plans operate under

the federal Employee Retirement Security Act which pre-empts state laws

that govern these plans.

Gaps and Barriers

Coverage for hepatitis B vaccination and other ACIP-recommended

vaccinations is greater for children and youths than for adults. Federal and

state funding for hepatitis B vaccination and other vaccinations provides a

safety net for the poorest children and youths, but no such program, such as

an adult version of the VFC program, exists for uninsured or underinsured

adults. Public Health Section 317 provides a potential vehicle for ﬁlling that

void, but funding has been increased only modestly since 2003 (Rodewald,

2008), and only recently has adult hepatitis B vaccination become a target

for some of the Section 317 funds. CDC has reported to Congress that it

would take about $1.6 billion—or 3 times the amount of current Section

317 funding—to ﬁll gaps in coverage and support to states to provide a

rigorous national vaccination program for children, adolescents, and adults,

including $335 million for payments to providers for all vaccine adminis-

tration (CDC, 2009d). In that report, CDC included only $49 million for

hepatitis B vaccine purchase for 675,000 high-risk adults in a total high-risk

population of 4.5 million people who visit STD-HIV and drug-treatment

centers—a 15% uptake. If uptake at those venues reached 74% for the

ﬁrst dose, as was observed at a San Diego STD clinic that combined free

vaccination with counseling (CDC, 2002), the cost for hepatitis B vaccine

purchase alone would approach $80 million.

Except for Medicaid’s Early Periodic Screening, Diagnosis, and Treat-

ment entitlement, public-health insurance often contains cost-sharing,

which may create a barrier to vaccination for some people. Adults covered

by Medicaid and Medicare and those being phased out of CHIP coverage

must share the costs of hepatitis B vaccination. Families of non-Medicaid

VFC-covered children may be responsible for the administration portion

of the vaccination cost.

Private health insurance has gaps for vaccination coverage because it

does not universally cover all ACIP-recommended vaccinations for children

and adults. Furthermore, most privately insured persons are required to pay

to receive vaccinations. More than two-thirds of privately insured persons

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IMMUNIZATION 135

are enrolled in non-HMO health plans that require deductibles to be met

before plan coverage and require out-of-pocket expenditures for services.

Recommendation 4-5. Private and public insurance coverage for hepa-

titis B vaccination should be expanded.

• Public Health Section 317 should be expanded with sufﬁcient fund-

ing to become the public safety net for underinsured and uninsured

adults to receive the hepatitis B vaccination.

• All private insurance plans should include coverage for all ACIP-

recommended vaccinations. Hepatitis B vaccination should be free

of any deductible so that ﬁrst-dollar coverage exists for this preven-

tive service.

Vaccine Accessibility

The hepatitis B vaccine is available at some physician ofﬁces, des-

ignated health clinics, and some community-based outreach programs.

However, many health-care providers’ ofﬁces do not offer vaccination, and

many US cities do not have health clinics or community-based programs

that provide the hepatitis B vaccine (Rein et al., 2010). Making the vaccine

available through nontraditional settings, such as pharmacies, would prob-

ably increase hepatitis B immunization rates in the United States. Previous

studies have shown that use of nontraditional settings, such as pharmacies

and supermarkets, to deliver vaccines to US adults results in increased ac-

cessibility and convenience, reduced cost, and increased public awareness

of the need for adult immunization (Postema and Breiman, 2000). That

strategy is also likely to be cost-saving (Prosser et al., 2008). The involve-

ment of community pharmacies in vaccine distribution and administration

has been growing in recent years (Westrick et al., 2009), and enlisting

their participation in public delivery of the hepatitis B vaccine is a natural

progression.

Vaccine-Supply Concerns

Several studies of vaccine supply in the United States have expressed

concerns regarding vaccine shortages (Jacobson et al., 2006; Klein and

Myers, 2006; Santoli et al., 2004). Reasons for vaccine shortages include

cessation of production by manufacturers due to lack of proﬁtability, li-

ability issues, problems with vaccine production, and unanticipated vaccine

demands (Klein and Myers, 2006; Santoli et al., 2004). From 2000 to 2004,

there were shortages of six pediatric vaccines: combined tetanus–diphtheria

toxoids (November 2000–June 2002), diphtheria–tetanus–acellular pertus-

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136 HEPATITIS AND LIVER CANCER

sis (March 2001–July 2002), pneumococcal conjugate (September 2001–

March 2003 and February 2004–September 2004), measles–mumps–rubella

(October 2001–July 2002), and varicella (October 2001–August 2002)

(Jacobson et al., 2006).

Although there has not been a national shortage of the hepatitis B

vaccine, temporary supply problems occurred with this vaccine in 2008

(adult and dialysis formulations of Recombivax HB) and 2009 (pediatric

formulations of Recombivax HB and Pediatric Engerix-B) (CDC, 2009a).

A shortage was avoided because other manufacturers were able to provide

an adequate supply of the vaccine in adult and dialysis formulations, and

CDC released doses of pediatric vaccine from its stockpile.

Recommendation 4-6. The federal government should work to ensure

an adequate, accessible, and sustainable hepatitis B vaccine supply.

HEPATITIS C VACCINE

Efforts are going on to develop a vaccine for hepatitis C, and several

candidates are in phase I and phase II clinical trials (Inchauspe and Michel,

2007). Although some vaccines are being developed to treat people with

chronic HCV infection (that is, therapeutic vaccines), this section focuses on

vaccines to prevent chronic HCV infection. An incomplete understanding

of how chronic HCV infection is spontaneously controlled in some people

and antigenic variability of the virus remain barriers to development of a

vaccine to prevent chronic hepatitis C.

Feasibility of Preventing Chronic Hepatitis C

The outcomes of HCV infections in humans and chimpanzees suggest

that it may be possible to develop a vaccine to prevent HCV infection.

Spontaneous clearance of the virus in 15–45% of persons after acute HCV

infection demonstrates that immunity can prevent chronic infection and its

long-term consequences, such as cirrhosis and hepatocellular carcinoma

(HCC) (Alter et al., 1992; Barrera et al., 1995; Villano et al., 1999; Vogt

et al., 1999). It also seems that immunity can be conditioned by prior ex-

posure: humans and chimpanzees that recover from HCV infection appear

to control a second infection better (the peak of viremia is lower than in

the initial infection, and the chance of recovery is greater compared with

that in persons not previously infected) (Lanford et al., 2004; Major et al.,

2002; Mehta et al., 2002). In addition, IDUs who recovered from earlier

HCV infections and have continuing HCV exposure have substantially less

viremia than those who have similar exposure but had no earlier infection

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IMMUNIZATION 137

(Mehta et al., 2002). Some hepatitis C vaccine candidates have shown

similar potential (Forns et al., 2000; Weiner et al., 2001).

Although those clinical observations suggest that it is possible to de-

velop a vaccine to prevent chronic HCV infection, there are important chal-

lenges. Immunity produced by natural infection does not prevent reinfection

(that is, it is not sterilizing); such immunity reduces the frequency of chronic

infection but does not prevent it (Farci et al., 1992). Moreover, the im-

munologic correlates of those critical clinical outcomes are not sufﬁciently

understood for rational design or evaluation of vaccine products. Marked

genetic variability in some HCV epitopes creates an especially formidable

challenge if immunity to them is necessary for protection.

Need for a Vaccine to Prevent Chronic Hepatitis C

Although HCV infections occur in the general population of the United

States and other economically developed countries, the incidence is prob-

ably too low to justify universal HCV vaccination. A hepatitis C vaccine

is most likely to beneﬁt populations that are at highest risk, include IDUs,

health-care workers who perform high-risk procedures, and some men who

report high-risk sexual practices with other men. A vaccine that prevents

chronic HCV infection not only might reduce the likelihood of long-term

disease, such as cirrhosis or HCC, but might reduce the likelihood of

secondary transmission by reducing the infection reservoir. It may not be

possible to produce a vaccine that prevents HCV infection, but a product

that prevents acute HCV infections from becoming chronic would probably

achieve many of the same beneﬁts. In cases where acute HCV infection does

not resolve within a few months, early treatment can prevent most cases

from evolving into chronic HCV infection. However, because most acute

HCV infections are not recognized, a vaccine is further likely to be of great-

est beneﬁt to populations in whom acute infection is rarely recognized and

treated (for example, IDUs).

Cost Effectiveness of a Hepatitis C Vaccine

Estimates of the cost effectiveness of hepatitis C vaccination depend

on a number of factors, including the cost of the vaccine, the target popu-

lation’s incidence, and projections of its effectiveness and duration. Several

studies have evaluated the potential cost effectiveness of an HCV vaccine

that prevents acute (and chronic) infection. Krahn et al. (2005) calculated

that if a hepatitis C vaccine with 80% efﬁcacy was available, had a dura-

tion of effectiveness equivalent to that of the hepatitis B vaccine, and was

cost-equivalent to that of the current hepatitis A vaccine ($51 per dose plus

administration fees), it would be cost saving to vaccinate IDUs. The authors

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138 HEPATITIS AND LIVER CANCER

also reported that vaccination of average-risk school-age children with such

a vaccine would be cost-effective. The cost would be about $18,000 per

QALY gained. Massad et al. (2009), on the basis of HCV incidence data for

Sao Paolo, Brazil, calculated that a 100% effective hepatitis C vaccine that

provides lifelong immunity and costs $300 per dose would cost $748,991

per death averted. If only high-risk people (for example, IDUs) were vacci-

nated, the cost would be $131,305 per death averted. If the hepatitis C vac-

cine had only 80% efﬁcacy and lifelong duration, it would cost $242,667

per death averted if given only to high-risk people.

The committee recognizes the need for a safe, effective, and affordable

hepatitis C vaccine. Such a vaccine could substantially enhance hepatitis C

prevention efforts.

Recommendation 4-7. Studies to develop a vaccine to prevent chronic

hepatitis C virus infection should continue.

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147

Viral Hepatitis Services

epatitis B virus (HBV) and hepatitis C virus (HCV) infections cause

substantial morbidity and mortality despite being preventable and

treatable. Deﬁciencies in the implementation of established guide-

lines for the prevention, diagnosis, and medical management of chronic

HBV and HCV infections perpetuate personal and economic burdens. This

chapter reviews the current status of services to prevent and manage chronic

hepatitis B and chronic hepatitis C. It then discusses the general components

of viral hepatitis services. The chapter ends with an assessment of gaps in

existing services, including a description of some models for services and

committee recommendations to improve viral hepatitis prevention and

management and to ﬁll research needs. Services for the general US popu-

lation are considered ﬁrst and then services for special populations and

service venues that have unique opportunities for interventions. Hepatitis

B immunization is covered in Chapter 4 and so is not discussed in detail

here.

The recommendations offered by the committee here are presented in

the context of the current health-care system in the United States. The com-

mittee believes strongly that if the system changes as a result of health-care

reform efforts, viral hepatitis services should have high priority in compo-

nents of the reformed system that deal with prevention, chronic disease, and

primary-care delivery. The committee’s recommendations regarding viral

hepatitis services are summarized in Box 5-1.

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148 HEPATITIS AND LIVER CANCER

CURRENT STATUS

Health services related to viral hepatitis prevention, screening, and

medical management are both limited and fragmented among entities at

the federal, state, and local levels. Numerous federal agencies administer

or fund some viral hepatitis–related services, including the Centers for

Disease Control and Prevention (CDC), the Health Resources and Services

BOX 5-1

Summary of Recommendations Regarding

Viral Hepatitis Services

General Population

• 5-1. Federally funded health-insurance programs—such as Medicare,

Medicaid, and the Federal Employees Health Beneﬁts Program—

should incorporate guidelines for risk-factor screening for hepatitis B

and hepatitis C as a required core component of preventive care so

that at-risk people receive serologic testing for hepatitis B virus and

hepatitis C virus and chronically infected patients receive appropriate

medical management.

Foreign-Born Populations

• 5-2. The Centers for Disease Control and Prevention, in conjunction

with other federal agencies and state agencies, should provide re-

sources for the expansion of community-based programs that provide

hepatitis B screening, testing, and vaccination services that target

foreign-born populations.

Illicit Drug Users

• 5-3. Federal, state, and local agencies should expand programs to

reduce the risk of hepatitis C virus infection through injection-drug use

by providing comprehensive hepatitis C virus prevention programs. At

a minimum, the programs should include access to sterile needle

syringes and drug-preparation equipment because the shared use of

these materials has been shown to lead to transmission of hepatitis

C virus.

• 5-4. Federal and state governments should expand services to reduce

the harm caused by chronic hepatitis B and hepatitis C. The services

should include testing to detect infection, counseling to reduce alcohol

use and secondary transmission, hepatitis B vaccination, and referral

for or provision of medical management.

• 5-5. Innovative, effective, multicomponent hepatitis C virus prevention

strategies for injection drug users and non-injection-drug users should

be developed and evaluated to achieve greater control of hepatitis C

virus transmission.

Pregnant Women

• 5-6. The Centers for Disease Control and Prevention should provide

additional resources and guidance to perinatal hepatitis B prevention

program coordinators to expand and enhance the capacity to identify

chronically infected pregnant women and provide case-management

services, including referral for appropriate medical management.

• 5-7. The National Institutes of Health should support a study of the

effectiveness and safety of peripartum antiviral therapy to reduce and

possibly eliminate perinatal hepatitis B virus transmission from women

at high risk for perinatal transmission.

Incarcerated Populations

• 5-8. The Centers for Disease Control and Prevention and the Depart-

ment of Justice should create an initiative to foster partnerships be-

tween health departments and corrections systems to ensure the

availability of comprehensive viral hepatitis services for incarcerated

people.

Community Health Facilities

• 5-9. The Health Resources and Services Administration should pro-

vide adequate resources to federally funded community health facili-

ties for provision of comprehensive viral-hepatitis services.

High Impact Settings

• 5-10. The Health Resources and Services Administration and the

Centers for Disease Control and Prevention should provide resources

and guidance to integrate comprehensive viral hepatitis services into

settings that serve high-risk populations such as STD clinics, sites for

HIV services and care, homeless shelters, and mobile health units.

Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C

http://www.nap.edu/catalog/12793.html

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