Prevention of Hepatitis B Virus Infection in the United States

U.S. Department of Health and Human Services

Centers for Disease Control and Prevention

Morbidity and Mortality Weekly Report

Recommendations and Reports / Vol. 67 / No. 1 January 12, 2018

Prevention of Hepatitis B Virus Infection in the

United States: Recommendations of the Advisory

Committee on Immunization Practices

Recommendations and Reports

The MMWR series of publications is published by the Center for Surveillance, Epidemiology, and Laboratory Services, Centers for Disease Control and Prevention (CDC),

U.S. Department of Health and Human Services, Atlanta, GA 30329-4027.

Suggested citation: [Author names; first three, then et al., if more than six.] [Title]. MMWR Recomm Rep 2018;67(No. RR-#):[inclusive page numbers].

Centers for Disease Control and Prevention

Brenda Fitzgerald, MD, Director

William R. Mac Kenzie, MD, Acting Associate Director for Science

Joanne Cono, MD, ScM, Director, Office of Science Quality

Chesley L. Richards, MD, MPH, Deputy Director for Public Health Scientific Services

Michael F. Iademarco, MD, MPH, Director, Center for Surveillance, Epidemiology, and Laboratory Services

MMWR Editorial and Production Staff (Serials)

Sonja A. Rasmussen, MD, MS, Editor-in-Chief

Charlotte K. Kent, PhD, MPH, Executive Editor

Christine G. Casey, MD, Editor

Teresa F. Rutledge, Managing Editor

David C. Johnson, Lead Technical Writer-Editor

Jeffrey D. Sokolow, MA, Project Editor

Martha F. Boyd, Lead Visual Information Specialist

Maureen A. Leahy, Julia C. Martinroe,

Stephen R. Spriggs, Tong Yang,

Visual Information Specialists

Quang M. Doan, MBA, Phyllis H. King,

Paul D. Maitland, Terraye M. Starr, Moua Yang,

Information Technology Specialists

MMWR Editorial Board

Timothy F. Jones, MD, Chairman

Matthew L. Boulton, MD, MPH

Virginia A. Caine, MD

Katherine Lyon Daniel, PhD

Jonathan E. Fielding, MD, MPH, MBA

David W. Fleming, MD

William E. Halperin, MD, DrPH, MPH

King K. Holmes, MD, PhD

Robin Ikeda, MD, MPH

Rima F. Khabbaz, MD

Phyllis Meadows, PhD, MSN, RN

Jewel Mullen, MD, MPH, MPA

Jeff Niederdeppe, PhD

Patricia Quinlisk, MD, MPH

Patrick L. Remington, MD, MPH

Carlos Roig, MS, MA

William L. Roper, MD, MPH

William Schaffner, MD

CONTENTS

Introduction ............................................................................................................1

New or Updated Recommendations .............................................................1

Methods ....................................................................................................................2

HBV Background ....................................................................................................3

Prophylaxis Against HBV Infection ..................................................................9

Recommendations ............................................................................................. 13

Future Directions ................................................................................................ 25

Acknowledgments ............................................................................................. 25

References ............................................................................................................. 25

Disclosure of Relationships

The 2016–2017 ACIP Hepatitis Vaccines Work Group

members wish to disclose that they have no financial or

competing interests with the manufacturers of commercial

products or suppliers of commercial services related to

hepatitis B (HepB) vaccines. Content will not include any

discussion of the unlabeled use of a product or a product under

investigational use, with the following exceptions:

• use of Pediarix vaccine for infants born to hepatitis B

surface antigen (HBsAg)–positive mothers or mothers

with an unknown HBsAg status to complete the vaccine

series after receipt of a birth dose of single-antigen HepB

vaccine and hepatitis B immune globulin (HBIG);

• alternate 3-dose vaccine administration schedules heeding

to minimum intervals of 4 weeks between the first and

second dose, 8 weeks between the second and third dose,

and 16 weeks between the first and third dose;

• modified dosing regimens (e.g., doubling of standard dose

and administration of additional doses) in certain

circumstances (e.g., for persons with immunocompromising

conditions); and

• antiviral therapy during pregnancy for the prevention of

perinatal hepatitis B virus (HBV) transmission.

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US Department of Health and Human Services/Centers for Disease Control and Prevention

Prevention of Hepatitis B Virus Infection in the United States:

Recommendations of the Advisory Committee

on Immunization Practices

Sarah Schillie, MD

Claudia Vellozzi, MD

Arthur Reingold, MD

Aaron Harris, MD

Penina Haber, MPH

John W. Ward, MD

Noele

P. Nelson, MD

Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, CDC

University of California, Berkeley School of Public Health, Berkeley, California

Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, CDC

Summary

Hepatitis B virus (HBV) is transmitted via blood or sexual contact. Persons with chronic HBV infection are at increased risk for

cirrhosis and liver cancer and require medical care. This report updates and summarizes previously published recommendations

from the Advisory Committee on Immunization Practices (ACIP) and CDC regarding the prevention of HBV infection in the

United States. ACIP recommends testing all pregnant women for hepatitis B surface antigen (HBsAg), and testing HBsAg-positive

pregnant women for hepatitis B virus deoxyribonucleic acid (HBV DNA); administration of HepB vaccine and hepatitis B immune

globulin (HBIG) for infants born to HBV-infected women within 12 hours of birth, followed by completion of the vaccine series and

postvaccination serologic testing; universal hepatitis B vaccination within 24 hours of birth, followed by completion of the vaccine

series; and vaccination of children and adolescents aged <19 years who have not been vaccinated previously. ACIP recommends

vaccination of adults at risk for HBV infection, including universal vaccination of adults in settings in which a high proportion

have risk factors for HBV infection and vaccination of adults requesting protection from HBV without acknowledgment of a

specific risk factor. These recommendations also provide CDC guidance for postexposure prophylaxis following occupational and

other exposures. This report also briefly summarizes previously published American Association for the Study of Liver Diseases

guidelines for maternal antiviral therapy to reduce perinatal HBV transmission.

Introduction

Hepatitis B virus (HBV) is transmitted through percutaneous

(i.e., puncture through the skin) or mucosal (i.e., direct contact

with mucous membranes) exposure to infectious blood or

body fluids. HBV is highly infectious, can be transmitted

in the absence of visible blood (1,2), and remains viable on

environmental surfaces for at least seven days (3). Persons

with chronic infection (e.g., those with persistent hepatitis B

surface antigen [HBsAg] in the serum for at least 6 months

following acute infection) serve as the main reservoir for HBV

transmission (4).

This report summarizes and consolidates previously

published recommendations from the Advisory Committee

on Immunization Practices (ACIP) and CDC. It also

Corresponding author: Sarah Schillie, Division of Viral Hepatitis,

National Center for HIV/AIDS, Viral Hepatitis, STD, and TB

Prevention, CDC. Telephone: 404-718-8608; E-mail: [email protected].

contains updates to recommendations for the prevention of

HBV infection in the United States. A list of frequently used

abbreviations is provided (Box 1).

New or Updated Recommendations

The following recommendations are new or updated:

• universal hepatitis B (HepB) vaccination within

24 hours of birth for medically stable infants weighing

≥2,000 grams;

• testing HBsAg-positive pregnant women for hepatitis B

virus deoxyribonucleic acid (HBV DNA);

• postvaccination serologic testing for infants whose

mother’s HBsAg status remains unknown indefinitely (e.g.,

when a parent or person with lawful custody surrenders

an infant confidentially shortly after birth);

• single-dose revaccination for infants born to HBsAg-

positive women not responding to the initial vaccine series;

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• vaccination for persons with chronic liver disease (including,

but not limited to, those with hepatitis C virus [HCV]

infection, cirrhosis, fatty liver disease, alcoholic liver disease,

autoimmune hepatitis, and an alanine aminotransferase

[ALT] or aspartate aminotransferase [AST] level greater than

twice the upper limit of normal); and

• removal of permissive language for delaying the birth dose

until after hospital discharge.

This report also briefly summarizes American Association for

the Study of Liver Diseases (AASLD) guidelines for maternal

antiviral therapy to reduce perinatal HBV transmission,

published previously (5). Recommendations from the

Infectious Diseases Society of America (IDSA) regarding

vaccination of the immunocompromised host are published

separately (6).

Methods

ACIP’s Hepatitis Work Group comprises professionals

from academic medicine (pediatrics, family medicine,

internal medicine, infectious disease, occupational health,

and preventive medicine specialists), federal and state public

health agencies, and medical societies.* The Work Group

reviewed epidemiology and literature, directed an economic

analysis, and deliberated upon recommendations. The

Work Group considered existing published ACIP and CDC

vaccine recommendations in summarizing recommendations

contained herein for the prevention of HBV infection.

This report updates and supplants ACIP recommendations

for HepB vaccination of children and adults published

previously (7,8). This report incorporates ACIP and CDC

recommendations published previously (9–11).

Guidelines from AASLD inform the use of antiviral

therapy among pregnant women with elevated HBV DNA

for the purpose of preventing perinatal HBV transmission.

Surveillance data were obtained from the National Notifiable

Diseases Surveillance System (NNDSS) (https://wwwn.cdc.

gov/nndss/).

Data informing clarifications to the recommendations were

summarized on the basis of findings from literature searches

that were completed on May 11, 2016. Two search terms were

used to ascertain data regarding maximum number of doses

for dialysis patients and minimum intervals for dialysis dosing:

“Hepatitis b vacc* dialysis boost*” and “Dialysis hepatitis b

vacc* schedule.” Epidemiologic and vaccine coverage data were

reviewed, as well as publicly available data on the number

of infant abandonments and safely surrendered infants. The

literature searches included clinical trials and comparative

* A list of the members appears on page 30.

BOX 1. Abbreviations used in this report

AASLD American Association for the Study of

Liver Diseases

ACIP Advisory Committee on Immunization

Practices

anti-HBc antibody to hepatitis B core antigen

anti-HBe antibody to hepatitis B e antigen

anti-HBs antibody to hepatitis B surface antigen

HBeAg hepatitis B e antigen

HBIG hepatitis B immune globulin

HBsAg hepatitis B surface antigen

HBV hepatitis B virus

HBV DNA hepatitis B virus deoxyribonucleic acid

HCP health care personnel

HCV hepatitis C virus

HepB hepatitis B

HIV human immunodeficiency virus

IDSA Infectious Diseases Society of America

IDU Injection-drug use

IgM Immunoglobulin class M

IgG Immunoglobulin class G

MSM men who have sex with men

NNDSS National Notifiable Diseases Surveillance

System

PHBPP Perinatal Hepatitis B Prevention Program

PWID persons who inject drugs

QALY quality-adjusted life-year

STI sexually transmitted infection

VAERS Vaccine Adverse Events Reporting System

VSD Vaccine Safety Datalink

studies conducted worldwide and published in English since

2000. All studies yielding pertinent information were eligible

for inclusion. Search results were supplemented by additional

relevant papers identified by subject matter experts on the

Work Group. Per the ACIP process, it was predetermined that

Grading of Recommendations Assessment, Development and

Evaluation (GRADE) was not required for these updates of

existing recommendations.

To assess vaccine safety, the Work Group searched two

postlicensure surveillance systems for adverse events from

2005 through 2015: the Vaccine Adverse Events Reporting

System (VAERS) (https://vaers.hhs.gov) and the Vaccine

Safety Datalink (VSD) (https://www.cdc.gov/vaccinesafety/

ensuringsafety/monitoring/vsd). VAERS is a national passive

surveillance system, and VSD conducts population-based

vaccine safety studies. VAERS can generate vaccine safety

hypotheses but cannot assess causality and is subject to several

limitations, including reporting biases and inconsistent data

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quality (12,13). VSD can be used to assess hypotheses that

arise from reviews of medical literature, reports to VAERS,

changes in immunization schedules, or the introduction of

new vaccines (14).

During February–September 2016, the Work Group held

five teleconference meetings. Work Group and ACIP members

also reviewed and commented on a draft of the statement prior

to the ACIP’s October 2016 meeting. A summary of Work

Group discussions was presented to ACIP on October 19, 2016.

At that time, ACIP members voted to approve a draft HepB

vaccine recommendations statement, including recommending

universal HepB vaccination within 24 hours of birth for

medically stable infants weighing ≥2,000 grams. In January

2017, the Work Group held a teleconference meeting to review

results of an economic analysis of single-dose revaccination

for infants born to HBsAg-positive women. Results from

that analysis were presented to ACIP on February 22, 2017.

Recommendations were not evaluated using GRADE, but

expert opinion was used to shape the recommendations. At

that time, ACIP members voted to approve language for single-

dose revaccination for infants (regardless of birth weight) born

to HBsAg-positive women. Modifications were made to the

ACIP statement during the subsequent review process at CDC

to update and clarify wording in the report.

HBV Background

Epidemiology

In 2015, a total of 3,370 cases of acute HBV infection

were reported to CDC. The actual number of acute cases is

believed to be 6.5 times the number of reported cases in any

year. It is estimated that 21,900 new cases of HBV occurred

in 2015 after under-ascertainment and under-reporting were

considered (4). The rate of reported acute HBV infections

declined 88.5% since recommendations for HepB vaccination

were first issued, from 9.6 cases per 100,000 population

in 1982 to 1.1 cases per 100,000 population in 2015 (15),

although the rate of acute HBV infections remained fairly

stable during 2010–2015 (4) (Figure 1). The 2015 incidence

is greatest for persons aged 30–39 years (2.6 per 100,000

population). In 2015, persons aged ≤19 years had the lowest

incidence (0.02 cases per 100,000 population), likely a result

of routine infant vaccination. Although the incidence of acute

HBV infection is greater for males than for females, the gap

has narrowed; in 2015, the rate for males was approximately

1.6 times higher than that for females (1.3 cases and 0.8 cases

per 100,000 population, respectively) (4). During 2009–2013,

the combined incidence of acute HBV infection in three states

(Kentucky, Tennessee, and West Virginia) increased 114% and

was associated with increasing injection-drug use (16).

On the basis of national health survey data, it is estimated

that approximately 850,000 persons are living with HBV

infection (prevalence) in the United States (17,18). Studies

based on data from countries of persons migrating to the

United States and census data indicate that the total prevalence

of chronic hepatitis B might be as high as 2.2 million persons

(19), suggesting that the national health survey-based estimate

might be conservative. Foreign-born persons account for

approximately 95% of newly reported chronic infections in the

United States (20); the prevalence of chronic HBV infection

is approximately 3.5% among foreign-born persons (19), and

the majority of chronic HBV infections in the United States

are among Asians/Pacific Islanders.

Strategy to Eliminate HBV

In 1991, the United States adopted a strategy for universal

HepB vaccination of infants (21). A comprehensive strategy

to eliminate HBV transmission evolved over the ensuing three

decades and encompasses 1) routine testing of all pregnant

women for HBsAg and prophylaxis for infants born to HBsAg-

positive mothers, 2) universal vaccination of infants beginning at

birth, 3) routine vaccination of previously unvaccinated children

and adolescents, and 4) vaccination of adults at risk for HBV

infection (7–11,21–26). Preventing perinatal transmission relies

upon testing all pregnant women for HBsAg and administering

timely prophylaxis (HepB vaccine and hepatitis B immune

globulin [HBIG]) to infants born to infected mothers. Universal

HepB vaccination of all infants beginning at birth provides a

critical safeguard and prevents infection among infants born

to HBsAg-positive mothers not identified prenatally (e.g., in

situations where the mother was not tested or when testing,

interpretation, or transcription errors occurred). Vaccination

of children and adolescents not previously vaccinated and

vaccination of adults at risk for HBV infection (e.g., by sexual

or percutaneous exposure and international travelers to certain

countries) is recommended to prevent HBV transmission outside

of the perinatal setting (Box 2).

HBV prevention strategies have been implemented

successfully in the United States, but challenges remain.

Approximately 88% of commercially insured women and

84% of Medicaid-enrolled women are tested for HBsAg

during pregnancy (27). In one study of a large health system

in northern California, 93% of HBsAg-positive pregnant

women were tested for HBV DNA (28). Most (94.9%) infants

born to infected women receive recommended prophylaxis

within 12 hours of birth (29). Universal HepB vaccine birth

dose coverage, defined as 1 dose of vaccine administered

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FIGURE 1. Incidence of hepatitis B virus infection — National Notifiable Diseases Surveillance System, United States, 1980–2015

100

150

200

250

300

350

Incidence (1,000s)

New Hepatitis B infections

1980 1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002 2004 2010 2012 20142006 2008

Years

Vaccine recs were

rst issued in 1982

by 3 days of life, is 71.1% (30), an increase from 50.1%

during 2003–2005 prior to revised ACIP recommendations

for the birth dose before hospital discharge (31), but below

the Healthy People 2020 target of 85% (32). HepB vaccine

coverage (≥3 doses) among children aged 19–35 months and

13–17 years is 90.5% (30) and 91.4% (33), respectively.

Vaccine coverage (≥3 doses) is lower among adults: 27.4%

among adults who report chronic liver conditions; 31.6%

among adults who traveled outside the United States to

countries other than Europe, Japan, Australia, New Zealand,

or Canada since 1995; and 24.4% among adults with

diabetes aged 19–59 years and 12.6% of adults with diabetes

aged ≥60 years (34). Among health care personnel (HCP),

≥3-dose coverage was 64.7%, an increase from 51% in 1992

shortly after implementation of the Needlestick Safety and

Prevention Act (35), but well below the Healthy People 2020

target of 90% (32,34).

New strategies for further reducing HBV transmission in

this report include testing HBsAg-positive pregnant women

for HBV DNA to identify infants at greatest risk for infection

and guide the use of maternal antiviral therapy (36,37).

Published evidence indicates that maternal antiviral therapy

during pregnancy further reduces perinatal HBV transmission;

hence, AASLD suggests antiviral therapy when maternal HBV

DNA is >200,000 IU/mL (5,38,39).

Virus Description and Transmission

HBV is a 40–42-nm enveloped virus classified in the

Hepadnaviridae family. HBV contains a circular, partially

double-stranded DNA genome that is 3.2 kb in length. After

a susceptible person is exposed, the virus enters the liver

via the bloodstream. The liver is the primary site of HBV

replication (40–43).

HBV has been classified by two separate systems: serologic

subtype and genotype. Nine serologic subtypes initially were

described based on the heterogeneity of HBsAg: adrq+, adrq–,

ayr, ayw1, ayw2, ayw3, ayw4, adw2, and adw4 (44,45). Ten

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HBV genotypes, designated A–J, have been described. HBV

serotypes and genotypes vary geographically. Infection or

immunization with one genotype generally confers immunity

to all genotypes (7,44,46,47).

HBV is highly infectious, can be transmitted in the absence

of visible blood (22), and remains infectious on environmental

surfaces for at least 7 days (2,3). All HBsAg-positive persons are

infectious, but those with elevated HBV DNA or those with

hepatitis B e antigen (HBeAg), a protein from the hepatitis B

virus that circulates in the blood and is a marker of infectivity,

are most infectious. Persons with occult HBV infection (i.e.,

those who test negative for HBsAg but have detectable HBV

DNA) also might transmit infection (48).

HBV is transmitted through percutaneous, mucosal,

or nonintact skin exposure to infectious blood or body

fluids. HBV is concentrated most highly in blood, and

percutaneous exposure is an efficient mode of transmission.

Semen and vaginal secretions are infectious, and HBV also

can be detected in saliva, tears, and bile. Cerebrospinal fluid,

synovial fluid, pleural fluid, peritoneal fluid, pericardial fluid,

and amniotic fluid are also considered potentially infectious.

Urine, feces, vomitus, nasopharyngeal washings, sputum,

and sweat are not efficient vehicles of transmission unless

they contain blood because they contain low quantities of

infectious HBV. HBsAg found in breast milk is also unlikely

to lead to transmission, and hence HBV infection is not a

contraindication to breastfeeding (2,7,22).

Among adults, HBV is transmitted primarily by percutaneous

exposure to blood (e.g., by injection-drug use) and sexual

contact. HBV is transmitted efficiently by sexual contact

both among heterosexuals and among men who have sex

with men (MSM). Risk factors for sexual transmission among

heterosexuals include having unprotected sex with an infected

partner, having unprotected sex with more than one partner,

and a history of another sexually transmitted infection (STI).

Risk factors associated with sexual transmission among MSM

include having multiple sex partners, history of another

STI, and anal intercourse. Transmission can occur from

interpersonal contact (e.g., sharing a toothbrush or razor,

contact with exudates from dermatologic lesions, or contact

with HBsAg-contaminated surfaces) and in settings such as

schools, child care centers, and facilities for developmentally

disabled persons. Transmission of HBV from transfusion of

blood or blood products is rare because of donor screening

and viral inactivation procedures. Other possible sources of

infection include contaminated medical or dental instruments,

unsafe injections, needle-stick injuries, organ transplantation,

and dialysis (49).

BOX 2. Strategy to eliminate HBV transmission in the United States*

• Screening of all pregnant women for HBsAg

– HBV DNA testing for HBsAg-positive pregnant

women, with suggestion of maternal antiviral

therapy to reduce perinatal transmission when

HBV DNA is >200,000 IU/mL

– Prophylaxis (HepB vaccine and HBIG) for infants

born to HBsAg-positive

†

women

• Universal vaccination of all infants beginning at

birth

§,¶

as a safeguard for infants born to HBV-

infected mothers not identified prenatally

• Routine vaccination of previously unvaccinated

children aged <19 years

• Vaccination of adults at risk for HBV infection,

including those requesting protection from HBV

without acknowledgment of a specific risk factor

* Sources: Mast EE, Margolis HS, Fiore AE, et al. A comprehensive

immunization strategy to eliminate transmission of hepatitis B virus

infection in the United States: recommendations of the Advisory

Committee on Immunization Practices (ACIP). Part 1: immunization of

infants, children, and adolescents. MMWR Recomm Rep 2005;54(No.

RR-16):1–31; Mast EE, Weinbaum CM, Fiore AE, et al. A comprehensive

immunization strategy to eliminate transmission of hepatitis B virus

infection in the United States: recommendations of the Advisory

Committee on Immunization Practices (ACIP). Part II: immunization

of adults. MMWR Recomm Rep 2006;55(No. RR-16):1–33.

†

Refer to Table 3 for prophylaxis recommendations for infants born to

women with unknown HBsAg status.

Within 24 hours of birth for medically stable infants weighing ≥2,000 grams.

Refer to Table 3 for birth dose recommendations for infants weighing

<2,000 grams.

Clinical Features and Natural History

Clinical manifestations of HBV infection range from

asymptomatic infection to fulminant hepatitis. The average

incubation period is 60 days (range: 40–90 days) from exposure

to onset of abnormal serum ALT levels and 90 days (range:

60–150 days) from exposure to onset of jaundice (8,42,43).

Infants, children aged <5 years, and immunosuppressed adults

with newly acquired HBV infection typically are asymptomatic,

whereas symptomatic illness is noted in 30%–50% of older

children, adolescents, and adults (7,8,44,50). When present,

signs and symptoms include nausea, vomiting, abdominal

pain, fever, dark urine, changes in stool color, hepatomegaly,

splenomegaly, and jaundice. Malaise and anorexia might

precede jaundice by 1–2 weeks. Fulminant HBV infection is

uncommon (<1%) but often results in death or liver failure

necessitating liver transplantation. Extrahepatic manifestations

of disease (e.g., skin rash, arthralgias, and arthritis) also might

occur (51). The fatality rate among persons with reported

cases of acute HBV infection is <1.5%, with the highest rates

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in adults aged ≥55 years. Because a substantial number of

infections are asymptomatic and therefore are not reported,

the overall fatality rate among all persons with HBV infection

is likely lower (8).

Chronic infection occurs among 80%–90% of persons

infected during infancy, 30% of persons infected before

age 6 years, and <1%–12% of persons infected as an older

child or adult (7,52–54). Approximately 95% of primary

infections in immunocompetent adults are self-limited, with

elimination of the virus from blood and generally immunity

to reinfection. Chronic infection develops more frequently

in immunosuppressed persons (e.g., hemodialysis patients

and persons with human immunodeficiency virus [HIV]

infection) (54,55) and persons with diabetes (54). Chronic

HBV infection can result in cirrhosis of the liver, liver cancer,

liver failure, and death. Approximately 25% of persons who

become chronically infected during childhood and 15% of

those who become chronically infected after childhood will

die prematurely from cirrhosis or liver cancer (8,56–58).

There are four phases of chronic HBV infection: immune

tolerant, immune active, immune inactive, and reactivation.

Chronically infected persons do not necessarily pass through

these phases in a linear fashion. Persons in the immune

tolerant phase have no or minimal hepatic inflammation or

fibrosis; most chronically infected children will remain in the

immune tolerant phase until late childhood or adolescence.

The immune active phase is characterized by an active immune

response resulting in hepatic inflammation, with or without

fibrosis. Persons who remain in the immune active phase

for prolonged periods of time are at high risk for developing

cirrhosis and hepatocellular carcinoma. Persons in the immune

inactive phase have improvement of hepatic inflammation and

fibrosis. Risk for progression to hepatocellular carcinoma is

lower among persons in the immune inactive phase compared

with the active phase. Persons in the reactivation phase have

active liver inflammation with or without fibrosis (44,59–61).

HBV reactivation might occur with immunosuppressive

therapy or treatment for HCV (62).

No specific treatment exists for acute HBV infection;

supportive care is the mainstay of therapy. Guidelines for

management of chronic HBV infection in children and adults,

including disease monitoring and antiviral therapy, are available

(5). Antiviral therapy generally should be initiated in patients

with chronic HBV infection who are likely to respond to

treatment and who are at high risk for liver-related morbidity

(5). Maternal antiviral therapy to reduce perinatal transmission

is suggested for HBsAg-positive pregnant women whose HBV

DNA level is >200,000 IU/mL (5).

In areas in which HBV is highly endemic, HBV frequently

is transmitted perinatally from HBV-infected pregnant women

to their newborns. The majority of cases of perinatal HBV

transmission occur during delivery, with rare instances of in

utero transmission (63). HBV transmission might occur in germ

cell lines, as the virus has been detected in sperm, oocytes, and

embryos. Available data do not support the need for a cesarean

delivery among HBV-infected pregnant women with low HBV

DNA (63). Prior to the widespread availability of postexposure

prophylaxis, the proportion of infants born to HBsAg-positive

women acquiring HBV infection was approximately 30% for

those born to HBeAg-negative mothers and 85% for those born

to HBeAg-positive mothers. With postexposure prophylaxis,

comprised of HepB vaccine and HBIG at birth, followed by

completion of the HepB vaccine series, 0.7%–1.1% of infants

develop infection (28,29,64); infants born to mothers with high

viral loads are at greatest risk for infection despite receipt of HepB

vaccine and HBIG (29). Unvaccinated infants and children are

also at risk for horizontal transmission from infected household

and other contacts.

Interpretation of Serologic Markers

Serologic markers for HBV infection include HBsAg,

antibody to HBsAg (anti-HBs), immunoglobulin class M

(IgM) antibodies to hepatitis B core antigen (IgM anti-HBc),

and immunoglobulin class G (IgG) anti-HBc (IgG anti-HBc)

(49,65,66). At least one serologic marker is present during

the different phases of infection. HBV DNA is a measure

of viral load and reflects viral replication (49) (Table 1).

Hepatitis B e antigen (HBeAg) can be detected in persons

with acute or chronic HBV infection; the presence of HBeAg

correlates with viral replication and high infectivity; antibody

to HBeAg (anti-HBe) correlates with the loss of replicating

virus, although reversion to HBeAg positivity can occur (7).

A confirmed positive HBsAg result indicates current HBV

infection, either acute or chronic. All HBsAg-positive persons are

infectious. If HBsAg persists for >6 months, spontaneous clearance

is unlikely, and the infection is deemed chronic. HBV DNA can

be detected prior to the detection of HBsAg in an infected person.

Occult infection occurs when HBsAg is undetectable despite the

presence of HBV DNA (66–68). Transient HBsAg positivity can

occur up to 18 days following vaccination (up to 52 days among

hemodialysis patients) and is clinically insignificant (69).

In acute HBV infection, anti-HBc (initially both IgM and

IgG) appears 1–2 weeks after the appearance of HBsAg (49)

(Figure 2). IgM anti-HBc often becomes undetectable within

6 months, and IgG anti-HBc predominates and remains

detectable for a lengthy period of time, often life-long (65,66).

The presence of IgM anti-HBc is indicative of acute infection,

while IgG anti-HBc indicates past infection (65,66). In persons

who recover from HBV infection, HBsAg is eliminated from

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TABLE 1. Typical interpretation of test results for hepatitis B virus infection

HBsAg Total anti-HBc IgM anti-HBc Anti-HBs HBV DNA Interpretation

- - - - - Never infected

+ - - - + or -

Early acute infection; transient (up to 18 days) after vaccination

+ + + - +

Acute infection

- + + + or - + or -

Acute resolving infection

- + - + -

Recovered from past infection and immune

+ + - - +

Chronic infection

- + - - + or -

False-positive (i.e., susceptible); past infection; “low-level” chronic infection; or passive

transfer of anti-HBc to infant born to HBsAg-positive mother

- - - + -

Immune if anti-HBs concentration is ≥10 mIU/mL after vaccine series completion;

passive transfer after hepatitis B immune globulin administration

Abbreviations: - = negative; + = positive; anti-HBc = antibody to hepatitis B core antigen; anti-HBs = antibody to hepatitis B surface antigen; HBsAg = hepatitis B

surface antigen; HBV DNA = hepatitis B virus deoxyribonucleic acid; IgM = immunoglobulin class M.

the blood and anti-HBs develops, typically within 3–4 months.

The presence of anti-HBs is generally indicative of immunity

to HBV infection (8). Anti-HBs also can be detected for 4–6

months following HBIG administration (10). Persons who

recover from natural HBV infection are typically positive for

both anti-HBs and anti-HBc, whereas persons who respond to

HepB vaccine are positive only for anti-HBs. Approximately

0.5%–2% of persons with chronic infection spontaneously

clear HBsAg yearly; anti-HBs will develop in the majority of

these persons (8).

In certain persons, anti-HBc is the only serologic marker

detected. Isolated anti-HBc-positivity can be detected

following HBV infection in persons who have recovered but

whose anti-HBs levels have waned; in populations with a

high prevalence of HBV infection, isolated anti-HBc likely

indicates previous infection with loss of anti-HBs. Some

chronically infected persons with isolated anti-HBc-positivity

have circulating HBsAg that is not detectable by a laboratory

assay. HBV DNA has been detected in <10% of persons with

isolated anti-HBc (70,71), although the presence of detectable

HBV DNA might fluctuate (72). These persons are unlikely to

transmit infection except under circumstances in which they

are the source of a large exposure, such as a blood transfusion

(8,73). Persons who are HBsAg-negative and anti-HBc-positive

can experience reactivation of infection during chemotherapy

or immunosuppressive therapy, with reappearance of HBsAg

(49). Infection with a mutant HBV strain can result in positive

laboratory tests for HBsAg, total anti-HBc, anti-HBs, and

HBV DNA, with a negative IgM anti-HBc.

Perinatal HBV infection in a child aged ≤24 months is

typically asymptomatic although fulminant hepatitis can occur;

a positive HBsAg test, positive HBeAg test, or detectable HBV

DNA may be considered laboratory evidence of perinatal HBV

in an infant born to an HBV-infected mother if timing criteria

are met (74). Infants who are born to HBsAg-positive mothers

and who do not become infected might have detectable

anti-HBc for up to 24 months after birth from passively

acquired maternal antibody (7).

Adults at Risk for HBV Infection

In 2015, CDC received 3,370 surveillance case-reports

of acute HBV infection. Of 2,207 case-reports with risk

information, 1,151 (52.2%) indicated no risk for HBV

during the 6 weeks to 6 months prior to illness onset, and the

remainder indicated at least one risk factor. Injection-drug use

and multiple sex partners were the most common reported

sources of HBV transmission (4).

Injection-drug use. Injection-drug use was reported by

30.3% of 1,657 new reported HBV cases that included

information about injection-drug use (4). Since 2009, there has

been an increase in acute HBV infection among non-Hispanic

whites aged 30–39 years residing in nonurban areas reporting

injection-drug use as a risk factor (16). Chronic HBV infection

has been identified in 3.5%-20.0% (midpoint estimate 11.8%)

of persons who inject drugs (PWID) in a variety of settings

(75) and 22.6% of PWID have evidence of past infection

(75). The proportion of HBV cases reporting injection-drug

use in three states (Kentucky, Tennessee, and West Virginia)

increased significantly, from 53% during 2006–2009 to 75%

during 2010–2013 (p<0.001, chi-square) (16).

Sexual (heterosexual and MSM) exposure. Among persons

with case-reports of HBV infection with information about

sexual exposure, 26.4% reported having two or more sexual

partners, 3.3% reported sexual contact with an HBV-infected

person, and 11.8% of males reported having had sex with

another male (4). As many as 10%–40% of adults seeking

treatment in STI clinics have evidence of current or past HBV

infection. Among adults with acute HBV infection, 39% were

screened or sought care for an STI prior to becoming infected

with HBV (76).

Household contacts. An estimated 45% of persons living

in households with others with chronic HBV infection have

serologic evidence of past HBV infection, and 16% have

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8 MMWR / January 12, 2018 / Vol. 67 / No. 1

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evidence of current infection (CDC, unpublished data, 2017).

Prior to universal infant vaccination, the risk for infection was

greatest among unvaccinated children living with a person

with chronic HBV infection in a household or in an extended

family setting (67,77,78).

Developmentally disabled persons in long-term-care

facilities. Developmentally disabled persons in residential

and nonresidential facilities historically have had a chronic

HBV infection prevalence as high as 20%. The prevalence of

infection has declined substantially since the implementation

of routine HepB vaccination in these settings (79–82).

Correctional facilities. The prevalence of chronic HBV

infection has been higher among prison inmates (1.0%–3.7%)

than among the general population (83,84), reflecting an

overrepresentation of persons entering correctional facilities

with risks for HBV infection (e.g., injection-drug use and

histories of multiple sex partners).

Persons at risk for occupational exposure to HBV. Before

HepB vaccination was widely implemented, HBV infection

was recognized as a common occupational risk among HCP

(85,86). Routine HepB vaccination of HCP and the use of

standard precautions have resulted in a 98% decline in HBV

infections from 1983 through 2010 among HCP (10). The

Occupational Safety and Health Administration mandates

that employers offer HepB vaccination to all employees who

have occupational risk and that postexposure prophylaxis be

available following an exposure (10,87).

Hemodialysis patients. Since the initiation of HepB

vaccination and additional infection control precautions for

hepatitis B in dialysis centers, the incidence of HBV infection

among hemodialysis patients has declined approximately 95%

(88,89). Since 1995, the annual incidence has been stable and

HBsAg seroprevalence has remained at 1% (90). Receipt of

dialysis was reported in <1% of acute HBV surveillance cases

with information reported to CDC (4).

Persons with HCV infection. The number of reported

HCV cases in four Appalachian states (Kentucky, Tennessee,

Virginia, and West Virginia) increased 364% during 2006–

2012 among persons aged ≤30 years, with injection-drug use

as the most common reported risk factor (91). The increase

in HCV infections occurred concomitantly with an increase

in HBV infections among young adults in rural communities

in Appalachian states.

Persons with chronic liver disease. Persons with chronic

liver disease (e.g., cirrhosis, fatty liver disease, alcoholic liver

disease, and autoimmune hepatitis) are not at increased risk

for HBV infection unless they have percutaneous or mucosal

FIGURE 2. Acute hepatitis B virus infection with recovery

Titer

Weeks after exposure

0 4 8 12 16 20 24 28 32 36 52 100

Total anti-HBc

IgM anti-HBc

Anti-HBs

HBsAg

HBV DNA

HBeAG Anti-HBe

Symptoms

Abbreviations: anti-HBc = antibody to hepatitis B core antigen; anti-HBe =

antibody to hepatitis B e antigen; anti-HBs = antibody to hepatitis B surface

antigen; HBeAg = hepatitis B e antigen; HBsAg = hepatitis B surface antigen; HBV

DNA = hepatitis B virus deoxyribonucleic acid; IgM = immunoglobulin class M.

exposure to blood or body fluids. However, concurrent chronic

HBV infection might increase the risk for progressive chronic

liver disease in these persons (92).

Travelers to countries where HBV is endemic. Short-

term travelers to countries in which HBV infection is of high

or intermediate endemicity (Box 3) typically are at risk for

infection only through exposure to blood in medical or disaster-

relief activities, receipt of medical care that involves parenteral

exposures, sexual activity, or drug use. Monthly incidence of

25‒420 per 100,000 travelers has been reported among long-

term travelers to countries where the disease is endemic (93).

Persons with HIV. Approximately 10% of HIV-positive

persons are coinfected with HBV (94–97). Chronic HBV

infection has been identified in 6%–14% of HIV-positive

persons, including in 9%–17% of MSM and in 7%–10%

of PWID (98). Coinfected persons have increased rates of

cirrhosis and liver-related mortality (99).

Persons with diabetes. Compared with adults without

diabetes, adults with diabetes have a 60% higher prevalence

of past or present HBV infection and twice the odds of

acquiring acute HBV. Repeated outbreaks of HBV infection

associated with assisted blood glucose monitoring underscore

the continued risk for this population (100–102). Data also

suggest the possibility of a higher case-fatality proportion

among persons with diabetes acutely infected with HBV

compared with those without diabetes (9).

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BOX 3. Prevalence of chronic hepatitis B virus infection, by country*

High (≥8% prevalence): Angola, Benin, Burkina Faso,

Burundi, Cameroon, Central African Republic, Congo,

Côte d’Ivoire, Djibouti, Equatorial Guinea, Gabon,

Gambia, Ghana, Guinea, Haiti, Kiribati, Kyrgyzstan, Laos,

Liberia, Malawi, Mali, Mauritania, Mongolia, Mozambique,

Namibia, Nauru, Niger, Nigeria, Niue, Papua New Guinea,

Senegal, Sierra Leone, Solomon Islands, Somalia, South

Sudan, Sudan, Swaziland, Togo, Tonga, Uganda, Vanuatu,

Vietnam, Yemen, and Zimbabwe.

Intermediate (5%–7.9% prevalence): Albania, Bhutan,

Cape Verde, China, Democratic Republic of the

Congo, Ethiopia, Kazakhstan, Kenya, Marshall Islands,

Moldova, Oman, Romania, Rwanda, Samoa, South

Africa, Tajikistan, Tanzania, Thailand, Tunisia, Tuvalu,

Uzbekistan, and Zambia.

Low Intermediate (2%–4.9% prevalence): Algeria,

Azerbaijan, Bangladesh, Belarus, Belize, Brunei Darussalam,

Bulgaria, Cambodia, Colombia, Cyprus, Dominican

Republic, Ecuador, Eritrea, Federated States of Micronesia,

Fiji, Georgia, Italy, Jamaica, Kosovo, Libya, Madagascar,

Myanmar, New Zealand, Pakistan, Palau, Philippines, Peru,

Russia, Saudi Arabia, Singapore, South Korea, Sri Lanka,

Suriname, Syria, Tahiti, and Turkey.

Low (≤1.9% prevalence): Afghanistan, Argentina,

Australia, Austria, Bahrain, Barbados, Belgium, Bolivia, Bosnia

and Herzegovina, Brazil, Canada, Chile, Costa Rica, Croatia,

Cuba, Czech Republic, Denmark, Egypt, France, Germany,

Greece, Guatemala, Hungary, Iceland, India, Indonesia,

Iran, Iraq, Ireland, Israel, Japan, Jordan, Kuwait, Lebanon,

Lithuania, Malaysia, Mexico, Morocco, Nepal, Netherlands,

Nicaragua, Norway, Palestine, Panama, Poland, Portugal,

Qatar, Serbia, Seychelles, Slovakia, Slovenia, Spain, Sweden,

Switzerland, Ukraine, UK, United Arab Emirates, United

States of America, and Venezuela.

No data: Andorra, Antigua and Barbuda, Armenia,

The Bahamas, Botswana, Chad, Comoros, Cook Islands,

Dominica, El Salvador, Finland, Grenada, Guinea-

Bissau, Guyana, Honduras, Latvia, Lesotho, Lithuania,

Luxembourg, Macedonia, Maldives, Malta, Mauritius,

Monaco, Montenegro, North Korea, Paraguay, Saint Kitts

and Nevis, Saint Lucia, Saint Vincent and the Grenadines,

San Marino, Sao Tome and Principe, Timor-Leste, Trinidad

and Tobago, Turkmenistan, and Uruguay.

* Source: CDC. Travelers health: infectious diseases related to travel. Atlanta, GA: US Department of Health and Human Services, CDC; 2017.

Prophylaxis Against HBV Infection

Hepatitis B Vaccines and

Hepatitis B Immune Globulins

HepB vaccination is the mainstay of HBV prevention

efforts; HBIG is generally used as an adjunct to HepB vaccine

in infants born to HBsAg-positive mothers and in certain

other postexposure prophylaxis situations. The first HepB

vaccines consisted of plasma-derived HBsAg. Recombinant

HepB vaccines containing yeast-derived HBsAg purified by

biochemical and biophysical separation techniques replaced the

plasma-derived vaccines in the United States by the late 1980s

(64,103,104). HepB vaccines recommended for use in the

United States are formulated to contain 10–40 µg of HBsAg

protein/mL and do not contain thimerosal as a preservative

(105). HBIG can augment protection until a response to

vaccination is attained. For those who do not respond to

HepB vaccination, HBIG administered alone is the primary

means of protection after an HBV exposure. HBIG provides

passively acquired anti-HBs and temporary protection (i.e.,

3–6 months). Passively acquired anti-HBs can be detected for

4–6 months after administration of HBIG (10).

HepB vaccines are available as a single-antigen formulation

and in combination with other vaccines. The two single-

antigen vaccines recommended for use in the United States,

Engerix-B (GlaxoSmithKline Biologicals, Rixensart, Belgium)

and Recombivax HB (Merck & Co., Inc., Whitehouse

Station, New Jersey), are used for the vaccination of persons

starting at birth. Of the two combination vaccines, Pediarix

(GlaxoSmithKline Biologicals, Rixensart, Belgium) is used for

the vaccination of persons aged 6 weeks–6 years and contains

recombinant HBsAg, diphtheria and tetanus toxoids and

acellular pertussis adsorbed, and inactivated poliovirus and

Twinrix (GlaxoSmithKline Biologicals, Rixensart, Belgium)

is used for the vaccination of persons aged ≥18 years and

contains recombinant HBsAg and inactivated hepatitis A virus

(Table 2). Comvax (Merck & Co., Inc., Whitehouse Station,

New Jersey), which was used previously for the vaccination of

persons aged 6 weeks–15 months and contained recombinant

HBsAg and Haemophilus b conjugate vaccine, has not been

available for purchase directly from Merck since January 1,

2015. Discontinuation of Comvax was not related to any

product safety or manufacturing issues. Aluminum salts

generally are used as adjuvants to enhance the immune response

of vaccinated persons.

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TABLE 2. Recommended doses of hepatitis B vaccine, by group and vaccine type

Age group (yrs)

Single-antigen vaccine Combination vaccine

Recombivax Engerix Pediarix* Twinrix

†

Dose (µg) Vol (mL) Dose (µg) Vol (mL) Dose (µg) Vol (mL) Dose (µg) Vol (mL)

Birth–10 5 0.5 10 0.5 10* 0.5 N/A N/A

11–15 10

1 N/A N/A N/A N/A N/A N/A

11–19 5 0.5 10 0.5 N/A N/A N/A N/A

≥20 10 1 20 1 N/A N/A 20

†

Hemodialysis patients and other immune-compromised persons

<20 5 0.5 10 0.5 N/A N/A N/A N/A

≥20 40 1 40 2 N/A N/A N/A N/A

Abbreviation: N/A = not applicable.

* Pediarix is approved for use in persons aged 6 weeks through 6 years (prior to the 7th birthday).

†

Twinrix is approved for use in persons aged ≥18 years.

Adult formulation administered on a 2-dose schedule.

Two HBIG products are licensed for use in the United States:

HepaGam B (Cangene Corporation, Winnipeg, Canada)

and Nabi-HB (Biotest Pharmaceuticals Corporation, Boca

Raton, Florida). HBIG is prepared from the plasma of donors

with high concentrations of anti-HBs. Source plasma tests

negative for evidence of HIV, HBV, and HCV. Investigational

nucleic acid testing for hepatitis A virus and parvovirus B19

also is performed on pooled samples of source plasma. The

manufacturing process contains two steps to inactivate viruses

in the final product: the solvent and detergent step inactivates

enveloped viruses, and the virus filtration step removes viruses

based on their size. HBIG products licensed for use in the

United States contain no preservative and are intended for

single use only (106).

Vaccine-Induced Seroprotection

The presence of anti-HBs typically indicates immunity

against HBV infection. Immunocompetent children and adults

who have vaccine-induced anti-HBs levels of ≥10 mIU/mL

1–2 months after having received a complete HepB vaccine

series are considered seroprotected and deemed vaccine

responders (107). Vaccine-induced seroprotection is considered

a surrogate of clinical protection. Anti-HBs levels wane

over time following vaccination related in part to the age at

vaccination. Approximately 16% of persons vaccinated at age

<1 year have antibody levels of ≥10 mIU/mL 18 years following

vaccination, compared with 74% for those vaccinated at

age ≥1 year (10). However, persons initially responding to

the full 3-dose HepB vaccine series and who are later found

to have anti-HBs <10 mIU/mL remain protected. Most

persons (88%) who receive a challenge dose of HepB vaccine

30 years after HepB vaccination as children or adults develop

an antibody response of ≥10 mIU/mL indicating persistent

immunity to HBV infection (108). Data from this and other

studies suggests protection against acute symptomatic and

chronic HBV infection persists for 30 years or more among

immunocompetent persons who originally responded to HepB

vaccine (108–110).

The 3-dose HepB vaccine series produces a protective

antibody response (anti-HBs ≥10 mIU/mL) in approximately

95% of healthy infants overall (response is lower for infants

with lower birth weights) (64) and >90% of healthy adults

aged <40 years (111,112). Among healthy infants, 25% and

63% achieve anti-HBs levels ≥10 mIU/mL after the first and

second dose, respectively. Among healthy adults aged <40 years,

30%–55% and 75% achieve anti-HBs levels ≥10 mIU/mL

after the first and second dose, respectively (7,8,64). Vaccine

response is decreased among infants weighing <2000 grams

and older adults. Other factors (e.g., smoking, obesity, aging,

chronic medical conditions, drug use, diabetes, male sex, genetic

factors, and immune suppression) contribute to a decreased

response to vaccine (113–116). Although immunogenicity is

lower among immunocompromised persons, those who achieve

and maintain seroprotective antibody levels before exposure

to HBV have a high level of protection (8).

Birth dose. A birth dose of HepB vaccine serves as

postexposure prophylaxis to prevent perinatal HBV infection

among infants born to HBV-infected mothers. Although

infants requiring postexposure prophylaxis should be identified

by maternal HBsAg testing, administration of a birth dose

to all infants (even without HBIG) serves as a safeguard to

prevent perinatal transmission among infants born to HBsAg-

positive mothers not identified prenatally because of lack of

maternal HBsAg testing or failures in reporting test results.

HepB vaccine or HBIG given alone are 75% and 71% effective

in preventing perinatal HBV transmission, respectively; their

combined efficacy is 94% (29,52,117). The birth dose also

provides protection to infants at risk from household exposure

after the perinatal period (29,64).

Vaccination produces seroprotection in 98% of healthy

term infants. Vaccine response is lower among infants with

birth weights <2000 grams (64). A study among low birth

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US Department of Health and Human Services/Centers for Disease Control and Prevention

weight infants demonstrated that more infants achieved

seroprotective anti-HBs levels when vaccine was initiated at

1 month of age versus within the first 3 days of life (96% vs.

68%, p<0.02) (118). Vaccine response among infants does

not vary appreciably by maternal HBsAg status or HBIG

administration (64).

Adolescents. Approximately 95% of adolescents achieve

seroprotection following HepB vaccination with a complete

series (7). The adult (10 µg) dose of Recombivax HB

administered using a 2-dose compressed schedule at 0 and

4 months or 0 and 6 months for persons aged 11–15 years

produces seroprotection proportions nearly equivalent to those

obtained with the standard regimen of 5 µg administered on

a 3-dose schedule at 0, 1, and 6 months (99.2% vs. 98.3%)

(119,120). Data on long-term antibody persistence or

protection among adolescents for 2-dose schedules are lacking.

Adults. Vaccination with a complete series results in

seroprotection in >90% of healthy adults aged <40 years.

Response decreases with age, and seroprotection is achieved

in 75% of persons aged 60 years (8).

Diabetes. A review of studies assessing HepB vaccine

response among persons with diabetes mellitus demonstrated

seroprotection in 93.9% for children with diabetes mellitus

compared with 100% for children without diabetes mellitus

(112,121).

Among adults, 88.2% of those with diabetes mellitus,

compared with 93.6% of those without diabetes mellitus,

achieved seroprotection (112). Among hemodialysis/chronic

kidney disease patients, the median proportion protected was

60.1% for those with diabetes mellitus, compared with 75.1%

for those without diabetes mellitus (112).

Immunocompromising conditions. The humoral

response to HepB vaccine is reduced in children and adults

who are immunocompromised (e.g., hematopoietic stem cell

transplant recipients, patients undergoing chemotherapy,

and HIV-infected persons) (122,123). Modified dosing

regimens, including a doubling of the standard antigen

dose or administration of additional doses, might increase

response rates. However, data on response to these alternative

vaccination schedules are limited (6).

Vaccine Safety

In prelicensure trials, adverse events following HepB

vaccination were most commonly injection site reactions

and mild systemic reactions (106). Commonly reported mild

adverse events from postmarketing data include pain (3%–

29%), erythema (3%), swelling (3%), fever (1%–6%), and

headache (3%) (124). The estimated incidence of anaphylaxis

among HepB vaccine recipients is 1.1 per million vaccine doses

(125). In 2011, the Institute of Medicine concluded that the

evidence convincingly supports a causal relationship between

HepB vaccine and anaphylaxis in yeast-sensitive persons, and

that the evidence is inadequate to accept or reject a causal

relation between HepB vaccine and several neurologic, chronic,

and autoimmune diseases (126).

During early postlicensure surveillance, several adverse

events following HepB vaccination have been described in

the scientific literature, including Guillain-Barré Syndrome

(GBS), chronic fatigue syndrome, optic neuritis, multiple

sclerosis, and diabetes mellitus; however, multiple studies

have demonstrated no association between receipt of HepB

vaccine and these conditions (126–129). In addition, no

evidence of a causal association between rheumatoid arthritis

(130), Bell’s palsy (131), autoimmune thyroid disease (132),

hemolytic anemia in children (133), anaphylaxis (134), optic

neuritis (135), Guillain-Barré Syndrome (136), sudden-onset

sensorineural hearing loss (137), or other chronic illnesses

and receipt of HepB vaccine has been demonstrated through

analysis of VSD data.

During 2005–2015, a total of 20,231 reports of adverse

events following HepB vaccination among all ages were

submitted to VAERS. The majority of primary U.S. reports

(15,787 of 20,231, 78%) were following HepB vaccine

administered with other vaccines on the same visit. Among

these, the percentage classified as serious (i.e., if one or more

of the following is reported: death, life-threatening illness,

hospitalization or prolongation of existing hospitalization,

or permanent disability)

†

was 16.7%, including 402 deaths,

of which 388 were among infants aged 6 weeks–23 months

(138). The most frequently reported adverse events for

vaccines given in combination were fever (23%), injection

site erythema (11%), and vomiting (10%) (138). Among the

4,444 single-antigen HepB reports, 6.5% were classified as

serious, including 43 deaths, of which 27 were among infants

aged ≤4 weeks. The most frequently reported adverse events

for single-antigen HepB vaccine were nausea/dizziness (8%)

and fever/headache (7%).

Vaccination Schedules

Vaccine schedules are determined on the basis of

immunogenicity data, and, for infants and children, the need

to integrate HepB vaccine into a harmonized immunization

schedule (Tables 3 and 4). Primary vaccination generally

consists of three intramuscular doses administered on a 0-,

1-, and 6-month schedule (Table 4). Recombivax HB may be

administered in a 2-dose schedule at 0 and 4–6 months for

†

Code of Federal Regulations. 21 CFR §600.80. Revised April 1, 2010. Available at

https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm? fr=600.80.

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TABLE 3. Hepatitis B vaccine schedules for infants, by infant birthweight and maternal HBsAg status

Birthweight Maternal HBsAg status

Single-antigen vaccine Single-antigen + combination vaccine

†

Dose Age Dose Age

≥2,000 g Positive 1 Birth (≤12 hrs) 1 Birth (≤12 hrs)

HBIG

Birth (≤12 hrs) HBIG Birth (≤12 hrs)

2 1–2 mos 2 2 mos

3 6 mos

3 4 mos

4 6 mos

Unknown* 1 Birth (≤12 hrs) 1 Birth (≤12 hrs)

2 1–2 mos 2 2 mos

3 6 mos

3 4 mos

4 6 mos

Negative 1 Birth (≤24 hrs) 1 Birth (≤24 hrs)

2 1–2 mos 2 2 mos

3 6–18 mos

3 4 mos

4 6 mos

<2,000 g Positive 1 Birth (≤12 hrs) 1 Birth (≤12 hrs)

HBIG Birth (≤12 hrs) HBIG Birth (≤12 hrs)

2 1 mos 2 2 mos

3 2–3 mos 3 4 mos

4 6 mos

Unknown 1 Birth (≤12 hrs) 1 Birth (≤12 hrs)

HBIG Birth (≤12 hrs) HBIG Birth (≤12 hrs)

2 1 mos 2 2 mos

3 2–3 mos 3 4 mos

4 6 mos

Negative 1 Hospital discharge or age 1 mo 1 Hospital discharge or age 1 mo

2 2 mos 2 2 mos

3 6–18 mos

3 4 mos

4 6 mos

Abbreviations: HBIG = hepatitis B immune globulin; HBsAg = hepatitis B surface antigen.

* Mothers should have blood drawn and tested for HBsAg as soon as possible after admission for delivery; if the mother is found to be HBsAg positive, the infant

should receive HBIG as soon as possible but no later than age 7 days.

†

Pediarix should not be administered before age 6 weeks.

HBIG should be administered at a separate anatomical site from vaccine.

The final dose in the vaccine series should not be administered before age 24 weeks (164 days).

persons aged 11–15 years using the adult formulation. Pediarix

is administered at ages 2, 4, and 6 months; it is not used for

the birth dose. Twinrix may be administered before travel or

any other potential exposure on an accelerated schedule at 0,

7, and 21–30 days, followed by a dose at 12 months. HepB

vaccination of adult hemodialysis patients consists of high-dose

(40 µg) Recombivax HB administered on a 0-, 1-, and 6-month

schedule or high-dose (40 µg) Engerix-B administered on a

0-, 1-, 2-, and 6-month schedule (106).

Alternative vaccination schedules (e.g., 0, 1, and 4 months

or 0, 2, and 4 months) have been demonstrated to elicit dose-

specific and final rates of seroprotection similar to those obtained

on a 0-, 1-, and 6-month schedule. Increasing the interval

between the first 2 doses has little effect on immunogenicity

or the final antibody concentration (139–141). The third dose

confers the maximum level of seroprotection and provides

long-term protection (142). Longer intervals between the

last 2 doses (e.g., 11 months) result in higher final antibody

levels (142) but might increase the risk for acquisition of

HBV infection among persons who have a delayed response

to vaccination. Higher geometric mean titers are associated

with longer persistence of measurable anti-HBs.

Response to Revaccination

A challenge dose of HepB vaccine may be used to determine

the presence of vaccine-induced immunologic memory

through generation of an anamnestic response. The term

“booster dose” has been used to refer to a dose of HepB vaccine

administered after a primary vaccination series to provide

rapid protective immunity against significant infection (i.e.,

infection resulting in serologic test results positive for HBV

and/or clinically significant disease). Among persons who were

vaccinated prior to age 1 year and found to have anti-HBs levels

<10 mIU/mL 6–18 years later, a single challenge dose of HepB

vaccine resulted in anti-HBs levels ≥10 mIU/mL in 60%–97%

of those tested. Similar results were found among persons

initially vaccinated at age ≥1 year (10). Immunocompetent

persons with a response ≥10 mIU/mL following a challenge

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dose are considered protected, regardless of subsequent declines

in anti-HBs (10,109).

One study found that of infants born to HBsAg-positive

women who were not infected at birth and who did not

respond to a primary vaccine series, all developed seroprotective

levels of anti-HBs after receipt of 3 additional doses (143). No

data exist that suggest that children who have no detectable

antibody after 6 doses of vaccine benefit from additional doses.

Maternal Antiviral Therapy for Preventing

Perinatal HBV Transmission

Antiviral therapy (i.e., lamivudine, telbivudine, and

tenofovir) has been studied as an intervention to reduce

perinatal HBV transmission among pregnant women with

high HBV DNA levels (e.g., average HBV DNA levels of

7.6 log10 IU/mL) (144). Maternal antiviral therapy started

at 28–32 weeks’ gestation, as an adjunct to HepB vaccine and

HBIG administered to the infant shortly after delivery, has

been associated with significantly reduced rates of perinatal

HBV transmission (5). The use of lamivudine and telbivudine

is limited by viral resistance and mutations. Tenofovir is not

associated with resistance and is the preferred agent (5).

Available data support the safety of tenofovir during pregnancy,

although its use might be associated with reduced bone mineral

content in infants with in utero exposure (5,39,63,144–146).

AASLD suggests antiviral therapy to reduce perinatal HBV

transmission when maternal HBV DNA is >200,000 IU/mL.

Maternal therapy is generally discontinued at birth to 3 months

postpartum (5).

Cost-Effectiveness Considerations

HBV prevention strategies targeting perinatal transmission

are considered very cost-effective (i.e., an incremental

cost-effectiveness ratio <$25,000). The current strategy of

administering HepB vaccine and HBIG within 12 hours of

birth for infants born to HBsAg-positive mothers and universal

infant vaccination prior to hospital discharge has an incremental

cost-effectiveness ratio of $6,957 per quality-adjusted life year

(QALY) saved when compared with a strategy of universal

infant HepB vaccination prior to hospital discharge alone

(147). CDC’s U.S. Perinatal Hepatitis B Prevention Program

(https://www.cdc.gov/hepatitis/partners/perihepbcoord.

htm), which provides case management services to infants

born to HBsAg-positive women, also has been demonstrated

to decrease infections, increase QALYs saved, and be a cost-

effective use of resources (148). A strategy of testing HBsAg-

positive pregnant women for HBV DNA, followed by maternal

antiviral prophylaxis for women with high HBV DNA, would

TABLE 4. Hepatitis B vaccine schedules for children, adolescents, and adults

Age group

Schedule* (interval represents time

in months from first dose)

Children (1–10 yrs) 0, 1, and 6 mos

0, 1, 2, and 12 mos

Adolescents (11–19 yrs) 0, 1, and 6 mos

0, 12, and 24 mos

0 and 4–6 mos

†

0, 1, 2, and 12 mos

0, 7 days, 21–30 days, 12 mos

Adults (≥20 yrs) 0, 1, and 6 mos

0, 1, 2, and 12 mos

0, 1, 2, and 6 mos

0, 7 days, 21–30 days, 12 mos

* Refer to package inserts for further information. For all ages, when the HepB

vaccine schedule is interrupted, the vaccine series does not need to be

restarted. If the series is interrupted after the first dose, the second dose should

be administered as soon as possible, and the second and third doses should

be separated by an interval of at least 8 weeks. If only the third dose has been

delayed, it should be administered as soon as possible. The final dose of vaccine

must be administered at least 8 weeks after the second dose and should follow

the first dose by at least 16 weeks; the minimum interval between the first and

second doses is 4 weeks. Inadequate doses of hepatitis B vaccine or doses

received after a shorter-than-recommended dosing interval should be

readministered, using the correct dosage or schedule. Vaccine doses

administered ≤4 days before the minimum interval or age are considered valid.

Because of the unique accelerated schedule for Twinrix, the 4-day guideline

does not apply to the first three doses of this vaccine when administered on a

0-day, 7-day, 21–30-day, and 12-month schedule (new recommendation).

†

A 2-dose schedule of Recombivax adult formulation (10 µg) is licensed for

adolescents aged 11–15 years. When scheduled to receive the second dose,

adolescents aged >15 years should be switched to a 3-dose series, with doses 2 and

3 consisting of the pediatric formulation administered on an appropriate schedule.

Twinrix is approved for use in persons aged ≥18 years and is available on an

accelerated schedule with doses administered at 0, 7, 21–30 days, and 12 months.

A 4-dose schedule of Engerix administered in two 1 mL doses (40 µg) on a 0-,

1-, 2-, and 6-month schedule is recommended for adult hemodialysis patients.

cost an additional $3 million but would save 2,080 QALYs and

prevent 324 chronic HBV infections, and therefore would be

considered cost-effective, with an incremental cost-effectiveness

ratio of $1,583 per QALY saved (36).

Cost-effectiveness also has been assessed for HBV prevention

strategies outside of the perinatal setting. Vaccinating adults

aged 20–59 years with diabetes mellitus costs $75,094 per

QALY saved; cost-effectiveness ratios increase with age at

vaccination (149). Among previously vaccinated current

HCP (including those in training), pre-exposure anti-HBs

testing followed by revaccination and retesting (if necessary,

based on anti-HBs levels), compared with no intervention,

was not considered cost-effective with an incremental cost per

QALY saved of $3–$4 million at year one and approximately

$800,000 over 10 years (150).

Recommendations

This section contains guidance for the prevention of HBV

infection, including ACIP recommendations for HepB

vaccination of infants, children, adolescents, and adults

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14 MMWR / January 12, 2018 / Vol. 67 / No. 1

US Department of Health and Human Services/Centers for Disease Control and Prevention

(Box 4) and CDC and ACIP recommendations for HBV

prophylaxis following occupational and nonoccupational

exposures, respectively.

Prevention of Perinatal HBV Transmission

Identification and Management of HBV-Infected

Pregnant Women

• All pregnant women should be tested for HBsAg during

an early prenatal visit (e.g., first trimester) in each

pregnancy, even if they have been vaccinated or tested

previously. Testing those pregnant women known to be

chronically infected with HBV provides documentation

of the positive HBsAg test result obtained during

pregnancy and helps to ensure that their infants will be

identified for timely prophylaxis.

– All HBsAg-positive pregnant women should be tested

for HBV DNA to guide the use of maternal antiviral

therapy during pregnancy for the prevention of

perinatal HBV transmission (new recommendation).

– AASLD suggests maternal antiviral therapy when the

maternal HBV DNA is >200,000 IU/mL

(new recommendation).

– All HBsAg-positive pregnant women should be referred

to their jurisdiction’s Perinatal Hepatitis B Prevention

Program (PHBPP) for case management to ensure that

their infants receive timely prophylaxis and follow-up.

A copy of the original laboratory report indicating the

pregnant woman’s HBsAg-positive status should be

provided to the hospital or birthing facility where the

delivery is planned and to the HCP who will care for

the newborn infant.

– All HBsAg-positive pregnant women should receive

information concerning HBV that discusses the

potential use of antiviral therapy, the importance of

prophylaxis for their infant (HepB vaccine and HBIG

within 12 hours of birth), completion of the vaccine

series, and postvaccination serologic testing.

• Women not tested prenatally, those with clinical hepatitis,

and those whose behaviors place them at high risk for

HBV infection (e.g., recent or current injection-drug use,

having had more than one sex partner in the previous

6 months or an HBsAg-positive sex partner, having been

evaluated or treated for a STI) should be tested at the time

of admission to the hospital or birthing facility for delivery.

• All laboratories that provide HBsAg testing of pregnant

women should use a Food and Drug Administration–

licensed or approved HBsAg test and should perform

testing according to the manufacturer’s labeling, including

BOX 4. Persons recommended to receive hepatitis B vaccination

• All infants

• Unvaccinated children aged <19 years

• Persons at risk for infection by sexual exposure

– Sex partners of hepatitis B surface antigen

(HBsAg)–positive persons

– Sexually active persons who are not in a long-term,

mutually monogamous relationship (e.g., persons

with more than one sex partner during the previous

6 months)

– Persons seeking evaluation or treatment for a

sexually transmitted infection

– 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 personnel with

reasonably anticipated risk for exposure to blood

or blood-contaminated body fluids

– Hemodialysis patients and predialysis, peritoneal

dialysis, and home dialysis patients

– Persons with diabetes aged 19–59 years; persons

with diabetes aged ≥60 years at the discretion of

the treating clinician

• Others

– International travelers to countries with high or

intermediate levels of endemic hepatitis B virus

(HBV) infection (HBsAg prevalence of ≥2%)

– Persons with hepatitis C virus infection

– Persons with chronic liver disease (including, but

not limited to, persons with cirrhosis, fatty liver

disease, alcoholic liver disease, autoimmune

hepatitis, and an alanine aminotransferase [ALT]

or aspartate aminotransferase [AST] level greater

than twice the upper limit of normal)

– Persons with HIV infection

– Incarcerated persons

– All other persons seeking protection from HBV

infection

testing of initially reactive specimens with a licensed

neutralizing confirmatory test. When pregnant women

are tested for HBsAg at the time of admission for delivery,

shortened testing protocols may be used and initially

reactive results reported to expedite administration of

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postexposure prophylaxis of infants. Commercial

laboratories should be encouraged to capture pregnancy

status for women tested for HBsAg to aid in identification

of HBV-infected pregnant women.

Management of Infants Born to Women Who Are

HBsAg-Positive

• All infants born to HBsAg-positive women should receive

HepB vaccine and HBIG within 12 hours of birth,

administered at different injection sites (e.g., separate

limbs). Only single-antigen HepB vaccine should be used

for the birth dose (Table 3).

• Infants born to women for whom HBsAg testing results

during pregnancy are not available but other evidence

suggestive of maternal HBV infection exists (e.g., presence

of HBV DNA, HBeAg-positive, or mother known to be

chronically infected with HBV) should be managed as if

born to an HBsAg-positive mother (new recommendation).

• The HepB vaccine series should be completed according

to the recommended schedule for infants born to HBsAg-

positive mothers. The final dose in the series should not

be administered before age 24 weeks (164 days). Although

not indicated in the manufacturers’ package labeling,

Pediarix may be used for infants aged ≥6 weeks born to

HBsAg-positive mothers to complete the vaccine series

after receipt of a birth dose of single-antigen HepB vaccine

and HBIG.

• For infants weighing <2,000 grams, the birth dose (i.e.,

the initial HepB vaccine dose) should not be counted as

part of the vaccine series because of the potentially reduced

immunogenicity of HepB vaccine in these infants; 3

additional doses of vaccine (for a total of 4 doses) should

be administered beginning when the infant reaches age

1 month. The final dose in the series should not be

administered before age 24 weeks (164 days).

• Postvaccination serologic testing for anti-HBs and HBsAg

should be performed after completion of the vaccine series

at age 9–12 months (generally at the next well-child visit

following completion of the HepB vaccine series).

Postvaccination serologic testing should be performed for

infants born to HBsAg-positive mothers and infants whose

mother’s HBsAg status remains unknown (i.e., those

infants who are safely surrendered shortly after birth) (new

recommendation). Anti-HBs testing should be performed

using a method that allows detection of the protective

concentration of anti-HBs (≥10 mIU/mL). Testing should

not be performed before age nine months to avoid

detection of passive anti-HBs from HBIG administered

at birth and to maximize the likelihood of detecting late

HBV infection. Anti-HBc testing of infants is not

recommended because passively acquired maternal anti-

HBc might be detected in infants born to HBsAg-positive

mothers up to age 24 months.

– HBsAg-negative infants with anti-HBs levels ≥10 mIU/

mL are protected and need no further medical management.

– HBsAg-negative infants with anti-HBs <10 mIU/mL

should be revaccinated with a single dose of HepB

vaccine and receive postvaccination serologic testing

1–2 months later (new recommendation). Infants

whose anti-HBs remains <10 mIU/mL following single

dose revaccination should receive two additional doses

of HepB vaccine to complete the second series followed

by postvaccination serologic testing 1–2 months after

the final dose.

– Based on clinical circumstances or family preference,

HBsAg-negative infants with anti-HBs <10 mIU/mL may

instead be revaccinated with a second, complete 3-dose

series, followed by postvaccination serologic testing

performed 1–2 months after the final dose of vaccine.

– Available data do not suggest a benefit from

administering additional HepB vaccine doses to infants

who have not attained anti-HBs ≥10 mIU/mL

following receipt of two complete HepB vaccine series.

– HBsAg-positive infants should be referred for

appropriate follow-up.

• Infants who are born to HBsAg-positive mothers and

receive postexposure prophylaxis may be breastfed

beginning immediately after birth.

• For infants transferred to a different facility after birth

(e.g., hospital with higher level of neonatal care), staff at

the transferring and receiving facilities should communicate

regarding the infant’s HepB vaccination and HBIG receipt

status to ensure prophylaxis is administered in a timely

manner (new recommendation).

Management of Infants Born to Women with

Unknown HBsAg Status

• Infants born to women for whom HBsAg testing results

during pregnancy are not available but other evidence

suggestive of maternal HBV infection exists (e.g., presence

of HBV DNA, HBeAg-positive, or mother known to be

chronically infected with HBV) should be managed as if

born to an HBsAg-positive mother (new recommendation).

The infant should receive both HepB vaccine and HBIG

within 12 hours of birth.

• Women admitted for delivery without documentation of

HBsAg test results should have blood drawn and tested as

soon as possible.

• While maternal HBsAg test results are pending, infants

with birth weights ≥2,000 grams born to women with an

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16 MMWR / January 12, 2018 / Vol. 67 / No. 1

US Department of Health and Human Services/Centers for Disease Control and Prevention

unknown HBsAg status should receive the first dose of

HepB vaccine (without HBIG) within 12 hours of birth.

Only single-antigen HepB vaccine should be used for the

birth dose (Table 3).

– If the mother is determined to be HBsAg-positive, the

infant should receive HBIG as soon as possible but no

later than age seven days, and the vaccine series should

be completed according to the recommended schedule

for infants born to HBsAg-positive mothers. The final

dose in the series should not be administered before

age 24 weeks (164 days). If the mother is determined

to be HBsAg-negative, the vaccine series should be

completed according to the recommended schedule for

infants born to HBsAg-negative mothers. The final

dose in the series should not be administered before

age 24 weeks (164 days).

• Because of the potentially decreased immunogenicity of

vaccine in infants weighing <2,000 grams, these infants

should receive both single-antigen HepB vaccine and

HBIG, administered at different injection sites (e.g.,

separate limbs), if the mother’s HBsAg status cannot be

determined within 12 hours of birth. The birth dose of

vaccine should not be counted as part of the 3 doses

required to complete the vaccine series; 3 additional doses

of vaccine (for a total of 4 doses) should be administered

according to a recommended schedule on the basis of the

mother’s HBsAg test result. The final dose in the series

should not be administered before age 24 weeks (164 days).

– If it is not possible to determine the mother’s HBsAg

status (e.g., when a parent or person with lawful custody

safely surrenders an infant confidentially shortly after

birth), the vaccine series should be completed according

to a recommended schedule for infants born to HBsAg-

positive mothers (new recommendation). The final

dose in the series should not be administered before

age 24 weeks (164 days). These infants should receive

postvaccination serologic testing at age 9–12 months,

and revaccination if necessary (new recommendation).

• Anti-HBs testing should be performed using a method

that allows detection of the protective concentration of

anti-HBs (≥10 mIU/mL). Testing should not be performed

before age nine months to avoid detection of passive anti-

HBs from HBIG administered at birth and to maximize

the likelihood of detecting late HBV infection. Anti-HBc

testing of infants is not recommended because passively

acquired maternal anti-HBc might be detected in infants

born to HBsAg-positive mothers up to age 24 months.

– HBsAg-negative infants with anti-HBs levels ≥10 mIU/mL

are protected and need no further medical management.

– HBsAg-negative infants with anti-HBs <10 mIU/mL

should be revaccinated with a single dose of HepB

vaccine and receive postvaccination serologic testing

1–2 months later (new recommendation). Infants

whose anti-HBs remains <10 mIU/mL following single

dose revaccination should receive two additional doses

of HepB vaccine to complete the second series, followed

by postvaccination serologic testing 1–2 months after

the final dose.

– Based on clinical circumstances or family preference,

HBsAg-negative infants with anti-HBs <10 mIU/mL may

instead be revaccinated with a second, complete 3-dose

series, followed by postvaccination serologic testing

performed 1–2 months after the final dose of vaccine.

– Available data do not suggest a benefit from

administering additional HepB vaccine doses to infants

who have not attained anti-HBs ≥10 mIU/mL

following receipt of two complete HepB vaccine series.

– HBsAg-positive infants should be referred for

appropriate follow-up.

• Infants born to mothers with unknown HBsAg status may

be breastfed beginning immediately after birth.

• For infants transferred to a different facility after birth

(e.g., a hospital with a higher level of neonatal care), staff

at the transferring and receiving facilities should

communicate regarding the infant’s HepB vaccination and

HBIG receipt status to ensure prophylaxis is administered

in a timely manner (new recommendation).

Persons Recommended for

HepB Vaccination

Universal Vaccination of Infants

• All infants should receive the HepB vaccine series as part

of the recommended childhood immunization schedule,

beginning at birth as a safety net (Box 4; Table 3).

• For all medically stable infants weighing ≥2,000 grams at

birth and born to HBsAg-negative mothers, the first dose

of vaccine should be administered within 24 hours of birth

(new recommendation). Only single-antigen HepB

vaccine should be used for the birth dose.

• Infants weighing <2,000 grams and born to HBsAg-

negative mothers should have their first vaccine dose

delayed to the time of hospital discharge or age 1 month

(even if weight is still <2,000 grams). For these infants, a

copy of the original laboratory report indicating that the

mother was HBsAg negative during this pregnancy should

be placed in the infant’s medical record. Infants weighing

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<2,000 grams at birth have a decreased response to HepB

vaccine administered before age 1 month (118).

• For infants transferred to a different facility after birth

(e.g., a hospital with a higher level of neonatal care), staff

at the transferring and receiving facilities should

communicate regarding the infant’s HepB vaccination and

HBIG receipt status to ensure prophylaxis is administered

in a timely manner (new recommendation).

• The final dose in the vaccine series should not be

administered before age 24 weeks (164 days).

• In populations with currently or previously high rates of

childhood HBV infection (e.g., Alaska Natives; Pacific

Islanders; and immigrant families from Asia, Africa, and

countries with intermediate or high endemic rates of

infection), the first dose of HepB vaccine should be

administered at birth and the final dose at age 6–12 months.

Vaccination of Children and Adolescents

• HepB vaccination is recommended for all unvaccinated

children and adolescents aged <19 years (Box 4).

• Children and adolescents who have not previously received

HepB vaccine should be vaccinated routinely at any age

(i.e., children and adolescents are recommended for

catch-up vaccination) (Table 4).

Vaccination of Adults

• HepB vaccination is recommended for all unvaccinated

adults at risk for HBV infection and for all adults requesting

protection from HBV infection. Acknowledgement of a

specific risk factor should not be a requirement for

vaccination (Box 4).

• Adults recommended to receive HepB vaccine:

– Persons at risk for infection by sexual exposure (e.g.,

sex partners of HBsAg-positive persons, sexually active

persons who are not in a mutually monogamous

relationship [e.g., persons with more than one sex

partner during the previous 6 months], persons seeking

evaluation or treatment for a sexually transmitted

infection, and MSM).

– Persons with a history of current or recent injection-

drug use are at increased risk for HBV infection. An

increased incidence of HBV incidence among young

adults in rural U.S. communities has been associated

with an increase in injection-drug use.

– Other persons at risk for infection by percutaneous or

mucosal exposure to blood (household contacts of

HBsAg-positive persons; residents and staff of facilities

for developmentally disabled persons; health care and

public safety personnel with reasonably anticipated risk

for exposure to blood or blood-contaminated body

fluids; hemodialysis patients and predialysis, peritoneal

dialysis, and home dialysis patients; persons with

diabetes mellitus aged <60 years and persons with

diabetes mellitus aged ≥60 years at the discretion of the

treating clinician).

– Others (international travelers to countries with high

or intermediate levels [HBsAg prevalence of ≥2%]

[Box 3] of endemic HBV infection, persons with HCV

infection, persons with chronic liver disease [including,

but not limited to, those with cirrhosis, fatty liver

disease, alcoholic liver disease, autoimmune hepatitis,

and an ALT or AST level greater than twice the upper

limit of normal] [new recommendation], persons with

HIV infection, incarcerated persons, all other persons

seeking protection from HBV infection without

acknowledgement of a specific risk factor).

Vaccination of Pregnant Women

• Pregnant women who are identified as being at risk for

HBV infection during pregnancy (e.g., having more than

one sex partner during the previous 6 months, been

evaluated or treated for an STI, recent or current injection-

drug use, or having had an HBsAg-positive sex partner)

should be vaccinated.

• Pregnant women at risk for HBV infection during

pregnancy should be counseled concerning other methods

to prevent HBV infection.

Implementation Strategies

Delivery Hospital Policies and Procedures

• All delivery hospitals and birthing facilities should implement

policies and procedures to ensure identification of infants

born to HBsAg-positive mothers and infants born to mothers

with unknown HBsAg status, initiation of prophylaxis for

these infants, and routine birth dose for medically stable

infants weighing ≥2,000 grams within 24 hours of birth. Such

policies and procedures should include standing orders and

electronic medical record reminders or prompts.

Case-Management Programs to Prevent Perinatal

HBV Infection

• States and localities should establish case-management

programs, including appropriate policies, procedures, laws,

and regulations to ensure that all pregnant women are

tested for HBsAg during each pregnancy, and that those

who are HBsAg-positive are tested for HBV DNA to guide

maternal antiviral therapy. Infants born to HBsAg-positive

women and women with unknown HBsAg status also

should receive case management.

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US Department of Health and Human Services/Centers for Disease Control and Prevention

Settings Providing Services to Adults

• In settings in which a high proportion of persons have risk

factors for HBV infection (e.g., health care settings

targeting services to injection-drug users, correctional

facilities, institutions and nonresidential day care facilities

for developmentally disabled persons), all adults should

be assumed to be at risk for HBV infection and should be

offered HepB vaccination if they have not previously

completed vaccination.

• HCP should implement standing orders to administer

HepB vaccine as part of routine services to adults who

have not completed the vaccine series and make HepB

vaccination a standard component of evaluation and

treatment for STIs and HIV/AIDS.

• When feasible, HepB vaccination should be offered in

outreach and other settings in which services are provided

to persons at risk for HBV infection (e.g., needle-exchange

programs, HIV testing sites, HIV prevention programs,

and homeless shelters).

• In medical settings, HCP should implement standing orders

to identify adults recommended for HepB vaccination and

administer vaccination as part of routine services.

Postexposure Prophylaxis

This section provides recommendations for management

of persons who are exposed to HBV through a distinct,

identifiable exposure to blood or body fluids that contain

blood, in occupational and nonoccupational settings.

• Wounds and skin sites that have been in contact with blood

or body fluids should be washed with soap and water; mucous

membranes should be flushed with water. Using antiseptics

(e.g., 2%–4% chlorhexidine) for wound care or expressing

fluid by squeezing the wound further have not been shown

to reduce the risk for HBV transmission; however, the use of

antiseptics is not contraindicated. The application of caustic

agents (e.g., bleach) or the injection of antiseptics or

disinfectants into the wound is not recommended.

Occupational Settings

Vaccinated HCP

• For vaccinated HCP (who have written documentation

of a complete HepB vaccine series) with subsequent

documented anti-HBs ≥10 mIU/mL, testing the source

patient for HBsAg is unnecessary. No postexposure

prophylaxis for HBV is necessary, regardless of the source

patient’s HBsAg status (Table 5).

• For vaccinated HCP (who have written documentation

of a complete HepB vaccine series) without previous anti-

HBs testing, the HCP should be tested for anti-HBs and

the source patient (if known) should be tested for HBsAg

as soon as possible after the exposure. Anti-HBs testing

should be performed using a method that allows detection

of the protective concentration of anti-HBs (≥10 mIU/mL).

Testing the source patient and the HCP should occur

simultaneously; testing the source patient should not be

delayed while waiting for the HCP anti-HBs test results,

and likewise, testing the HCP should not be delayed while

waiting for the source patient’s HBsAg results (Table 5).

– If the HCP has anti-HBs <10 mIU/mL and the source

patient is HBsAg-positive or has an unknown HBsAg

status, the HCP should receive 1 dose of HBIG and

be revaccinated as soon as possible after the exposure.

HepB vaccine may be administered simultaneously

with HBIG at a separate anatomical injection site (e.g.,

separate limb). The HCP should then receive the

second 2 doses of HepB vaccine to complete the second

series (likely 6 doses total when accounting for the

original series) according to the vaccination schedule.

So the HCP’s vaccine response status can be documented

TABLE 5. Postexposure management of health care personnel after occupational percutaneous or mucosal exposure to blood or body fluids,

by health care personnel HepB vaccination and response status

HCP status

Postexposure testing Postexposure prophylaxis

Postvaccination

serologic testing

Source patient

(HBsAg) HCP testing (anti-HBs) HBIG Vaccination

Documented responder after complete series No action needed

Documented nonresponder after two

complete series

Positive/unknown * HBIG x2 separated by

1 month



N/A

Negative No action needed

Response unknown after complete series Positive/unknown <10 mIU/mL HBIG x1 Initiate revaccination Yes

Negative <10 mIU/mL None Initiate revaccination Yes

Any result ≥10 mIU/mL No action needed

Unvaccinated/incompletely vaccinated or

vaccine refusers

Positive/unknown



HBIG x1 Complete vaccination Yes

Negative



None Complete vaccination Yes

Abbreviations: anti HBs = antibody to hepatitis B surface antigen; HBIG = hepatitis B immune globulin; HBsAg = hepatitis B surface antigen; HCP = health care

personnel; N/A = not applicable.

* Not indicated.

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for future exposures, anti-HBs testing should be

performed 1–2 months after the final vaccine dose.

– If the HCP has anti-HBs <10 mIU/mL and the source

patient is HBsAg-negative, the HCP should receive an

additional single HepB vaccine dose, followed by repeat

anti-HBs testing 1–2 months later. HCP whose anti-

HBs remains <10 mIU/mL should undergo

revaccination with two more doses (likely 6 doses total

when accounting for the original series). So the HCP’s

vaccine response status can be documented for future

exposures, anti-HBs testing should be performed

1–2 months after the final dose of vaccine.

– If the HCP has anti-HBs ≥10 mIU/mL at the time of

the exposure, no postexposure HBV management is

necessary, regardless of the source patient’s HBsAg status.

• For vaccinated HCP with anti-HBs <10 mIU/mL after

two complete HepB vaccine series, the source patient

should be tested for HBsAg as soon as possible after the

exposure. If the source patient is HBsAg-positive or has

unknown HBsAg status, the HCP should receive 2 doses

of HBIG (1,10). The first dose should be administered as

soon as possible after the exposure, and the second dose

should be administered 1 month later. HepB vaccine is

not recommended for the exposed HCP who has

previously completed two HepB vaccine series. If the

source patient is HBsAg-negative, neither HBIG nor HepB

vaccine is necessary (Table 5).

Unvaccinated HCP

• For unvaccinated or incompletely vaccinated HCP, the

source patient should be tested for HBsAg as soon as

possible after the exposure. Testing unvaccinated or

incompletely vaccinated HCP for anti-HBs is not

necessary and is potentially misleading, because anti-HBs

≥10 mIU/mL as a correlate of vaccine-induced protection

has only been determined for persons who have completed

an approved vaccination series (107) (Table 5).

• If the source patient is HBsAg-positive or has an unknown

HBsAg status, the HCP should receive 1 dose of HBIG

and 1 dose of HepB vaccine administered as soon as

possible after the exposure. HepB vaccine may be

administered simultaneously with HBIG at a separate

anatomical injection site (e.g., separate limb). The HCP

should complete the HepB vaccine series according to the

vaccination schedule. To document the HCP’s vaccine

response status for future exposures, anti-HBs testing

should be performed approximately 1–2 months after the

final vaccine dose. Anti-HBs testing should be performed

using a method that allows detection of the protective

concentration of anti-HBs (≥10 mIU/mL). Because

anti-HBs testing of HCP who received HBIG should be

performed after anti-HBs from HBIG is no longer

detectable (6 months after administration), it might be

necessary to defer anti-HBs testing for a period longer

than 1–2 months after the last vaccine dose in these

situations (Table 5).

– HCP with anti-HBs ≥10 mIU/mL after receipt of the

primary vaccine series are considered immune.

Immunocompetent persons have long-term protection

and do not need further periodic testing to assess anti-

HBs levels.

– HCP with anti-HBs <10 mIU/mL after receipt of the

primary series should be revaccinated. For these HCP,

administration of a second complete series on an

appropriate schedule, followed by anti-HBs testing

1–2 months after the final dose, is usually more

practical than conducting serologic testing after each

additional dose of vaccine. So the HCP’s vaccine

response status can be documented for future exposures,

anti-HBs testing should be performed 1–2 months after

the final vaccine dose.

• If the source patient is HBsAg-negative, the HCP should

complete the HepB vaccine series according to the

vaccination schedule. So the HCP’s vaccine response status

can be documented for future exposures, anti-HBs testing

should be performed approximately 1–2 months after the

final vaccine dose (Table 5).

– HCP with anti-HBs ≥10 mIU/mL after receipt of the

primary vaccine series are considered immune.

Immunocompetent persons have long-term protection

and do not need further periodic testing to assess anti-

HBs levels.

– HCP with anti-HBs <10 mIU/mL after receipt of the

primary series should be revaccinated. For these HCP,

administration of a second complete series on an

appropriate schedule, followed by anti-HBs testing

1–2 months after the final dose, is usually more practical

than conducting serologic testing after each additional

dose of vaccine. So the HCP’s vaccine response status

can be documented for future exposures, anti-HBs

testing should be performed 1–2 months after the final

vaccine dose.

Clinical Management of Exposed HCP

• HCP who have anti-HBs <10 mIU/mL (or who are

unvaccinated or incompletely vaccinated) and sustain an

exposure to a source patient who is HBsAg-positive or has

an unknown HBsAg status should undergo baseline testing

for HBV infection as soon as possible after the exposure,

and follow-up testing approximately 6 months later. Testing

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20 MMWR / January 12, 2018 / Vol. 67 / No. 1

US Department of Health and Human Services/Centers for Disease Control and Prevention

immediately after the exposure should consist of total anti-

HBc, and follow-up testing approximately 6 months later

should consist of HBsAg and total anti-HBc.

• HCP exposed to a source patient who is HBsAg-positive

or has an unknown HBsAg status do not need to take

special precautions to prevent secondary transmission

during the follow-up period; however, they should refrain

from donating blood, plasma, organs, tissue, or semen

(10). The exposed HCP does not need to modify sexual

practices or refrain from becoming pregnant (10). If an

exposed HCP is breastfeeding, she does not need to

discontinue (7,10). No modifications to an exposed HCP’s

patient-care responsibilities are necessary to prevent

transmission to patients based solely on exposure to a

source patient who is HBsAg-positive or has an unknown

HBsAg status.

Previously Vaccinated HCP

• Providers should only accept written, dated records as

evidence of HepB vaccination (151).

• An increasing number of HCP have received routine HepB

vaccination during childhood. No postvaccination

serologic testing is recommended after routine infant or

adolescent HepB vaccination. Because vaccine-induced

anti-HBs wanes over time, testing HCP for anti-HBs years

after vaccination might not distinguish vaccine

nonresponders from responders. Pre-exposure assessment

of current or past anti-HBs results upon hire or

matriculation, followed by one or more additional doses

of HepB vaccine for HCP with anti-HBs <10 mIU/mL

and retesting anti-HBs, if necessary, helps to ensure that

HCP will be protected if they have an exposure to HBV-

containing blood or body fluids (Box 5; Figure 3).

– HCP who cannot provide documentation of 3 doses

of HepB vaccine should be considered unvaccinated

and should complete the vaccine series. Postvaccination

serologic testing for anti-HBs is recommended

1–2 months after the third vaccine dose. HCP who are

inadvertently tested before receiving 3 documented

doses of HepB vaccine and have anti-HBs ≥10 mIU/mL

should not be considered immune because anti-HBs

≥10 mIU/mL is a known correlate of protection only

when testing follows a documented 3-dose series.

Health care facilities are encouraged to try to locate

vaccine records for HCP and to enter all vaccine doses

in their state immunization information system.

Nonoccupational Settings

HBsAg-Positive Source

This section provides recommendations for management

of persons who are exposed to HBV through a distinct,

identifiable exposure to blood or body fluids that contain

blood, in nonoccupational settings (Table 6). The exposed

person does not need to undergo postvaccination serologic

testing following vaccination based solely on being exposed.

• Exposed persons who have written documentation of a complete

HepB vaccine series and who did not receive postvaccination

testing should receive a single dose of HepB vaccine.

• Exposed persons who are in the process of being vaccinated

but who have not completed the vaccine series should receive

a dose of HBIG and complete the HepB vaccine series (it

is not necessary to restart the HepB vaccine series). HepB

vaccine may be administered simultaneously with HBIG

at a separate anatomical injection site (e.g., separate limb).

• Exposed unvaccinated persons should receive both HBIG

and HepB vaccine as soon as possible after exposure

(preferably within 24 hours). HepB vaccine may be

administered simultaneously with HBIG at a separate

anatomical injection site (e.g., separate limbs). Studies are

limited on the maximum interval after exposure during

which postexposure prophylaxis is effective, but the

interval is unlikely to exceed 7 days for percutaneous

exposure and 14 days for sexual exposures. The HepB

vaccine series should be completed according to the

vaccination schedule.

HBsAg-Unknown Source

• Exposed persons with written documentation of a

complete HepB vaccine series require no further treatment.

• Exposed persons who are in the process of being vaccinated

but who are not fully vaccinated should complete the

HepB vaccine series (it is not necessary to restart the

vaccination series).

• Exposed unvaccinated persons should receive the HepB

vaccine series with the first dose administered as soon as

possible after exposure, preferably within 24 hours. Studies

are limited on the maximum interval after exposure during

which postexposure prophylaxis is effective, but the interval

is unlikely to exceed 7 days for percutaneous exposure and

14 days for sexual exposures. The vaccine series should be

completed according to the vaccination schedule.

Recommendations and Reports

MMWR / January 12, 2018 / Vol. 67 / No. 1 21

US Department of Health and Human Services/Centers for Disease Control and Prevention

Immunization Management Issues

Prevaccination Testing

• Vaccination of persons immune to HBV because of current

or previous infection or HepB vaccination does not

increase the risk for adverse events (8). However, in

populations that have high rates of previous HBV

infection, prevaccination testing might reduce costs by

avoiding vaccination of persons who are already immune.

Prevaccination testing consists of testing for HBsAg, anti-

HBs, and anti-HBc. Serologic testing should not be a

barrier to vaccination of susceptible persons, especially in

populations that are difficult to access. Testing is not a

requirement for vaccination, and in settings where testing

is not feasible, vaccination of recommended persons

should continue.

• The first dose of HepB vaccine should typically be

administered immediately after collection of the blood for

serologic testing. Prevaccination testing is recommended

for the following persons (Box 6):

– household, sexual, or needle-sharing contacts of

HBsAg-positive persons;

– HIV-positive persons;

– persons with elevated alanine aminotransferase (ALT)/

aspartate aminotransferase (AST) of unknown etiology;

– hemodialysis patients (refer to 2001 CDC

recommendations [88] for additional information);

– MSM; and

– past or current injection-drug users.

Testing for HBV Infection

• Testing for HBV infection (consisting of testing for

HBsAg, anti-HBs, and anti-HBc) is also recommended

for the following persons:

– persons born in countries of high and intermediate

HBV endemicity (HBsAg prevalence ≥2%);

– U.S.-born persons not vaccinated as infants whose

parents were born in countries with high HBV

endemicity (≥8%);

– persons needing immunosuppressive therapy, including

chemotherapy, immunosuppression related to organ

transplantation, and immunosuppression for

rheumatologic or gastroenterologic disorders; and

– donors of blood, plasma, organs, tissues, or semen.

• All pregnant women should be tested for HBsAg

during each pregnancy. Pregnant women with positive

HBsAg tests should be tested for HBV DNA.

Postvaccination Serologic Testing

• Serologic testing for immunity is not necessary after

routine vaccination of infants, children, or adults.

• Testing for anti-HBs after vaccination is recommended

for the following persons whose subsequent clinical

management depends on knowledge of their immune

status (Box 7):

– infants born to HBsAg-positive women and infants

born to women whose HBsAg status remains unknown

BOX 5. Testing anti-HBs for health care personnel (HCP) vaccinated

in the past

The issue: An increasing number of HCP have received

routine hepatitis B (HepB) vaccination during childhood.

No postvaccination serologic testing is recommended after

routine infant or adolescent HepB vaccination. Because

vaccine-induced antibody to hepatitis B surface antigen

(anti-HBs) wanes over time, testing HCP for anti-HBs

years after vaccination might not distinguish vaccine

nonresponders from responders.

Guidance for health care institutions: Health

care institutions may measure anti-HBs upon hire or

matriculation for HCP who have documentation of a

complete HepB vaccine series in the past (e.g., as part

of routine infant or adolescent vaccination). HCP with

anti-HBs <10 mIU/mL should receive one or more

additional doses of HepB vaccine and retesting (Figure 3).

Institutions that decide to not measure anti-HBs upon hire

or matriculation for HCP who have documentation of a

complete HepB vaccine series in the past should ensure

timely assessment and postexposure prophylaxis following

an exposure (Table 5).

Considerations: The risk for occupational HBV

infection for vaccinated HCP might be low enough in

certain settings so that assessment of anti-HBs status

and appropriate follow-up should be done at the time of

exposure to potentially infectious blood or body fluids. This

approach relies on HCP recognizing and reporting blood

and body fluid exposures and therefore may be applied

on the basis of documented low risk, implementation,

and cost considerations. Certain HCP occupations have

lower risk for occupational blood and body fluid exposures

(e.g., occupations involving counseling versus performing

procedures), and nontrainees have lower risks for blood

and body fluid exposures than trainees. Some settings

also will have a lower prevalence of HBV infection in the

patient population served than in other settings, which will

influence the risk for HCP exposure to HBsAg-positive

blood and body fluids.

Recommendations and Reports

22 MMWR / January 12, 2018 / Vol. 67 / No. 1

US Department of Health and Human Services/Centers for Disease Control and Prevention

FIGURE 3. Pre-exposure evaluation for health care personnel previously vaccinated with complete, ≥3-dose HepB vaccine series who have

not had postvaccination serologic testing*

Measure antibody to hepatitis B surface antigen (anti-HBs)

anti-HBs

≥10 mIU/mL

anti-HBs

<10 mIU/mL

anti-HBs

<10 mIU/mL

anti-HBs

≥10 mIU/mL

Administer 1 dose of HepB vaccine,

postvaccination serologic testing

Administer 2 more doses

of HepB vaccine,

postvaccination serologic testing

anti-HBs <10 mIU/mL anti-HBs ≥10 mIU/mL

No action for

hepatitis B prophylaxis

(regardless of source patient

hepatitis B surface antigen status)

Health care

personnel need

to receive

hepatitis B

evaluation for

all exposures

Source: Adapted from CDC. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations

of the Advisory Committee on Immunization Practices (ACIP). Part II: immunization of adults. MMWR 2006;55(No. RR-16).

* Should be performed 1–2 months after the last dose of vaccine using a quantitative method that allows detection of the protective concentration of anti-HBs

(≥10 mIU/mL) (e.g., enzyme-linked immunosorbent assay [ELISA]).

Recommendations and Reports

MMWR / January 12, 2018 / Vol. 67 / No. 1 23

US Department of Health and Human Services/Centers for Disease Control and Prevention

TABLE 6. Postexposure management after distinct nonoccupational percutaneous or mucosal exposure to blood or body fluids

Exposure*

Management

Unvaccinated person Previously vaccinated person

HBsAg-positive source HepB vaccine series and HBIG HepB vaccine dose

HBsAg status unknown for source Hep B vaccine series No management

Abbreviations: HepB = hepatitis B; HBsAg = hepatitis B surface antigen; HBIG = hepatitis B immune globulin.

* Exposures include percutaneous (e.g., bite or needlestick) or mucosal exposure to blood or body fluids, sex or needle-sharing contact, or victim of sexual assault/abuse.

(e.g., infants safely surrendered shortly after birth).

Postvaccination serologic testing should consist of

testing for anti-HBs and HBsAg;

– HCP and public safety workers at risk for blood or

body fluid exposure;

– hemodialysis patients (and other persons who might

require outpatient hemodialysis), HIV-infected

persons, and other immunocompromised persons (e.g.,

hematopoietic stem-cell transplant recipients or persons

receiving chemotherapy), to determine the need for

revaccination and the type of follow-up testing; and

– sex partners of HBsAg-positive persons, to determine

the need for revaccination and for other methods of

protection against HBV infection.

• Testing should be performed 1–2 months after

administration of the final dose of the vaccine series using

a method that allows determination of a protective

concentration of anti-HBs (≥10 mIU/mL).

– Persons found to have anti-HBs concentrations of

≥10 mIU/mL after the primary vaccine series are

considered to be immune.

– Immunocompetent persons have long-term protection and

do not need further periodic testing to assess anti-HBs levels.

– Immunocompromised persons might need annual testing

to assess anti-HBs concentrations (See Revaccination).

– Persons found to have anti-HBs concentrations of

<10 mIU/mL after the primary vaccine series should

be revaccinated. Administration of all doses in the

second series, on an appropriate schedule, followed by

anti-HBs testing 1–2 months after the final dose, is

usually more practical than serologic testing after one

or more doses of vaccine (except for when revaccinating

infants born to HBsAg-positive mothers).

– Persons who do not have a protective concentration of

anti-HBs after revaccination should be tested for HBsAg.

– If the HBsAg test result is positive, the person should

receive appropriate management, and any household,

sexual, or needle-sharing contacts should be identified and

vaccinated. Prevaccination testing (consisting of anti-HBc,

HBsAg, and anti-HBs) to identify infected persons is

recommended for household, sexual, or needle-sharing

contacts of HBsAg-positive persons; serologic testing

should not be a barrier to vaccination, and the first HepB

vaccine dose should be administered immediately after

collection of the blood for serologic testing.

– Persons who test negative for HBsAg should be

considered susceptible to HBV infection and should

be counseled about precautions to prevent HBV

infection and the need to obtain HBIG postexposure

prophylaxis for any known or likely exposure to an

HBsAg-positive source (10).

• Testing HCP with documentation of complete HepB

vaccination for anti-HBs upon hire or matriculation (i.e.,

pre-exposure assessment of prior response to HepB

vaccination), followed by one or more additional doses of

HepB vaccine for HCP with anti-HBs <10 mIU/mL, helps

to ensure that HCP will be protected if they have an

exposure to HBV-containing blood or body fluids.

• Anti-HBs levels of ≥10 mIU/mL are generally considered

seroprotective; however, different assays have different

assay cutoff values based on which reported levels of anti-

HBs might vary depending on the assay used. Refer to the

package insert of the test for the determination of actual/

correct levels of anti-HBs antibodies.

Revaccination

• Revaccination (i.e., booster dose, challenge dose, or

revaccination with a complete series) is not generally

recommended for persons with a normal immune status

who were vaccinated as infants, children, adolescents, or

adults. Available data do not suggest a maximum number

of booster doses. Revaccination when anti-HBs is

<10 mIU/mL is recommended for the following persons:

– Infants born to HBsAg-positive mothers. HBsAg-

negative infants with anti-HBs <10 mIU/mL should

be revaccinated with a single dose of HepB vaccine,

and retested 1–2 months later. Infants whose anti-HBs

remains <10 mIU/mL following single dose

revaccination should receive two additional doses of

HepB vaccine on a vaccine schedule to complete the

second series, followed by anti-HBs testing 1–2 months

later. Alternatively, these infants may be revaccinated

with a second 3-dose series and retested (HBsAg and

anti-HBs) 1–2 months after the final dose of vaccine.

Recommendations and Reports

24 MMWR / January 12, 2018 / Vol. 67 / No. 1

US Department of Health and Human Services/Centers for Disease Control and Prevention

BOX 6. Persons recommended to receive serologic testing prior

to vaccination*

• Household, sexual, or needle contacts of hepatitis B

surface antigen (HBsAg)–positive persons

†

• HIV-positive persons

†

• Persons with elevated alanine aminotransferase/

aspartate aminotransferase of unknown etiology

†

• Hemodialysis patients

†

• Men who have sex with men

†

• Past or current persons who inject drugs

†

• Persons born in countries of high and intermediate

hepatitis B virus (HBV) endemicity (HBsAg

prevalence ≥2%)

• U.S.-born persons not vaccinated as infants whose

parents were born in countries with high HBV

endemicity (≥8%)

• Persons needing immunosuppressive therapy,

including chemotherapy, immunosuppression related

to organ transplantation, and immunosuppression for

rheumatologic or gastroenterologic disorders

• Donors of blood, plasma, organs, tissues, or semen

* Serologic testing comprises testing for hepatitis B surface antigen (HBsAg),

antibody to HBsAg, and antibody to hepatitis B core antigen.

†

Denotes persons also recommended for hepatitis B vaccination. Serologic

testing should occur prior to vaccination. Serologic testing should not be a

barrier to vaccination of susceptible persons. The first dose of vaccine should

typically be administered immediately after collection of the blood for

serologic testing.

– HCP. Completely vaccinated HCP with anti-HBs

<10 mIU/mL should receive an additional dose of HepB

vaccine, followed by anti-HBs testing 1–2 months later.

HCP whose anti-HBs remains <10 mIU/mL should

complete the second series (usually 6 doses total), followed

by repeat anti-HBs testing 1–2 months after the final dose.

Alternatively, it might be more practical for very recently

vaccinated HCP with anti-HBs <10 mIU/mL to receive

the second complete series (usually 6 doses total), followed

by anti-HBs testing 1–2 months after the final dose.

– Hemodialysis patients. For hemodialysis patients

treated in outpatient centers, the need for booster doses

should be assessed by annual anti-HBs testing. A

booster dose should be administered when anti-HBs

levels decline to <10 mIU/mL. Anti-HBs testing

1–2 months following the booster dose to assess

response is not recommended.

– Other immunocompromised persons. For other

immunocompromised persons (e.g., HIV-infected

persons, hematopoietic stem-cell transplant recipients, and

persons receiving chemotherapy), the need for booster

doses has not been determined. Annual anti-HBs testing

and booster doses should be considered for persons with

an ongoing risk for exposure.

Interrupted Schedules and Minimum

Dosing Intervals

• For all ages, when the HepB vaccine schedule is

interrupted, the vaccine series does not need to be

restarted. If the series is interrupted after the first dose,

the second dose should be administered as soon as possible,

and the second and third doses should be separated by an

interval of at least 8 weeks. If only the third dose has been

delayed, it should be administered as soon as possible. The

final dose of vaccine must be administered at least 8 weeks

after the second dose and should follow the first dose by

at least 16 weeks; the minimum interval between the first

and second doses is 4 weeks. Inadequate doses of

HepB vaccine or doses received after a shorter-than-

recommended dosing interval should be readministered,

using the correct dosage or schedule.

• Vaccine doses administered ≤4 days before the minimum

interval or age are considered valid. Because of the unique

accelerated schedule for Twinrix, the 4-day guideline does

not apply to the first 3 doses of this vaccine when

administered on a 0-day, 7-day, 21–30-day, and 12-month

schedule (new recommendation).

• In infants, administration of the final dose is not

recommended before age 24 weeks.

Other Immunization Management Issues

• No differences in immunogenicity have been observed

when one or 2 doses of HepB vaccine produced by one

manufacturer are followed by doses from a different

manufacturer (8). Whenever feasible, the same vaccine

should be used for the subsequent doses; however, if a

different brand is administered, the dose should be

considered valid and does not need to be repeated.

• Providers should only accept dated records as evidence of

HepB vaccination.

• Although vaccinations should not be postponed if records

cannot be found, an attempt to locate missing records

should be made by contacting previous health care

providers, reviewing state or local immunization

information systems, and searching for a personally held

record. If records cannot be located within a reasonable

time, these persons should be considered susceptible and

started on the age-appropriate vaccination schedule. An

anti-HBs ≥10 mIU/mL is a serologic correlate of protection

only when following a documented, complete series.

Recommendations and Reports

MMWR / January 12, 2018 / Vol. 67 / No. 1 25

US Department of Health and Human Services/Centers for Disease Control and Prevention

BOX 7. Persons recommended to receive postvaccination serologic

testing* following a complete series of HepB vaccination

• Infants born to hepatitis B surface antigen (HBsAg)–

positive mothers or mothers whose HBsAg status

remains unknown (e.g., when a parent or person with

lawful custody safely surrenders an infant confidentially

shortly after birth infants safely surrendered at or

shortly after birth)

†

• Health care personnel and public safety workers

• Hemodialysis patients and others who might require

outpatient hemodialysis (e.g., predialysis, peritoneal

dialysis, and home dialysis)

• HIV-infected persons

• Other immunocompromised persons (e.g.,

hematopoietic stem-cell transplant recipients or

persons receiving chemotherapy)

• Sex partners of HBsAg-positive persons

* Postvaccination serologic testing for persons other than infants born to

HBsAg-positive (or HBsAg-unknown) mothers consists of anti-HBs.

†

Postvaccination serologic testing for infants born to HBsAg-positive (or

HBsAg-unknown) mothers consists of anti-HBs and HBsAg. Persons

with anti-HBs <10 mIU/mL after the primary vaccine series should be

revaccinated. Infants born to HBsAg-positive mothers or mothers with

an unknown HBsAg status should be revaccinated with a single dose of

HepB vaccine and receive postvaccination serologic testing 1–2 months

later. Infants whose anti-HBs remains <10 mIU/mL following single dose

revaccination should receive two additional doses of HepB vaccine,

followed by postvaccination serologic testing 1–2 months after the final

dose. Based on clinical circumstances or family preference, HBsAg-

negative infants with anti-HBs <10 mIU/mL may instead be revaccinated

with a second, complete 3-dose series, followed by postvaccination

serologic testing performed 1–2 months after the final dose of vaccine.

For others with anti-HBs <10 mIU/mL after the primary series,

administration of 3 additional HepB vaccine doses on an appropriate

schedule, followed by anti-HBs testing 1–2 months after the final dose,

is usually more practical than serologic testing after ≥1 dose of vaccine.

• In all settings, vaccination should be initiated even though

completion of the series might not be ensured.

• Adverse events occurring after administration of any vaccine

should be reported to VAERS. Reports should be submitted

to VAERS online, by facsimile, or by mail. More information

about VAERS is available by calling 1-800-822-7967 (toll-

free) or online at https://vaers.hhs.gov.

Future Directions

ACIP and CDC will review these recommendations as new

epidemiology or other information related to HepB vaccines

(including licensure of additional HepB-containing vaccines),

HepB vaccine adverse events, and the experience gained in the

implementation of these recommendations becomes available.

Revised recommendations will be developed as needed.

Acknowledgments

Mona Doshani, Alaya Koneru, Henry Roberts, PhD, Division of

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

STD, and TB Prevention, CDC.

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Recommendations and Reports

30 MMWR / January 12, 2018 / Vol. 67 / No. 1

US Department of Health and Human Services/Centers for Disease Control and Prevention

Advisory Committee on Immunization Practices

Membership as of September 16, 2016

Chair: Nancy Bennett, MD, University of Rochester School of Medicine and Dentistry, Rochester, New York.

Executive Secretary: Amanda Cohn, MD, National Center for Immunization and Respiratory Diseases, CDC, Atlanta, Georgia.

Members: Robert Atmar, MD, Baylor College of Medicine, Houston, Texas; Edward Belongia, MD, Marshfield Clinic Research Foundation, Marshfield,

Wisconsin; Echezona Ezeanolue, MD, University of Nevada, Las Vegas, Nevada; Paul Hunter, MD, City of Milwaukee Health Department, Milwaukee,

Wisconsin; Allison Kempe, MD, University of Colorado School of Medicine, Denver, Colorado; Grace Lee, MD, Boston Children’s Hospital, Boston,

Massachusetts; Kelly Moore, MD, Tennessee Department of Health, Nashville, Tennessee; Cynthia Pellegrini, March of Dimes, District of Columbia;

Arthur Reingold, MD, University of California, Berkeley School of Public Health, Berkeley, California; Laura Riley, MD, Harvard Medical School, Boston,

Massachusetts; José Romero, MD, University of Arkansas for Medical Sciences, Little Rock, Arkansas; David Stephens, MD, Emory University, Atlanta,

Georgia; Peter Szilagyi, MD, University of California, Los Angeles, California; Emmanuel (Chip) Walter, Jr., MD, Duke University School of Medicine,

Durham, North Carolina.

Ex Officio Members: Bruce Gellin, MD, National Vaccine Program Office, District of Columba; Richard Gorman, MD, National Institutes of Health, Bethesda,

Maryland; Amy Groom, MPH, Indian Health Service, Albuquerque, New Mexico; Mary Beth Hance, Centers for Medicare and Medicaid Services, Baltimore,

Maryland; Jane Kim, MD, Department of Veterans Affairs, Durham, North Carolina; Narayan Nair, MD, Health Resources and Services Administration,

Rockville, Maryland; Eric Sergienko, MD, Department of Defense, Atlanta, Georgia; Wellington Sun, MD, Food and Drug Administration, Bethesda, Maryland.

Liaison Representatives: American Academy of Family Physicians, Margot Savoy, MD, Wilmington, Delaware; American Academy of Pediatrics, Carrie

Byington, MD, Salt Lake City, Utah; American Academy of Pediatrics, Red Book Editor, David Kimberlin, MD, Birmingham, Alabama; American Academy of

Physician Assistants, Marie-Michèle Léger, MPH, Alexandria, Virginia; American College Health Association, Susan Even, MD, Columbia, Missouri; American

College of Nurse Midwives, Carol Hayes, MN, MPH, Atlanta, Georgia; American College of Nurse Midwives Alternate, Pamela Meharry, PhD, Chicago,

Illinois; American College of Obstetricians and Gynecologists, Kevin Ault, MD, Kansas City, Kansas; American College of Physicians, Sandra Fryhoffer, MD,

Atlanta, Georgia; American College of Physicians Alternate, Gregory Poland, MD, Rochester, Minnesota; American Geriatrics Society, Kenneth Schmader,

MD, Durham, North Carolina; America’s Health Insurance Plans, Mark Netoskie, MD, Houston, Texas; American Medical Association, Sandra Fryhoffer,

Atlanta, Georgia; American Nurses Association, Charles Rittle, DNP, Pittsburgh, Pennsylvania; American Osteopathic Association, Stanley Grogg, DO, Tulsa,

Oklahoma; American Pharmacists Association, Stephan L. Foster, PharmD, Memphis, Tennessee; Association of Immunization Managers, Christine Finley,

MPH, Burlington, Vermont; Association for Prevention and Teaching Research, Paul McKinney, MD, Louisville, Kentucky; Association of State and Territorial

Health Officials, Terry Dwelle MD, Bismarck, North Dakota; Biotechnology Industry Organization, Phyllis Arthur, District of Columbia.; Council of State

and Territorial Epidemiologists, Christine Hahn, MD, Boise, Idaho; Canadian National Advisory Committee on Immunization, Ian Gemmill, MD, Kingston,

Ontario, Canada; Infectious Diseases Society of America, Kathleen Neuzil, MD, Seattle, Washington; Infectious Disease Society of America Alternate, Carol

Baker, MD, Houston, Texas; National Association of County and City Health Officials, Matthew Zahn, MD, Santa Ana, California; National Association

of County and City Health Officials, Jeffrey Duchin, MD, Seattle, Washington; National Association of Pediatric Nurse Practitioners, Patricia Stinchfield,

MPH, St. Paul, Minnesota; National Foundation for Infectious Diseases, William Schaffner, MD, Nashville, Tennessee; National Immunization Council

and Child Health Program, Mexico; Ignacio Villasenor Ruiz, MD, Mexico; National Medical Association, Patricia Whitley-Williams, MD, New Brunswick,

New Jersey; National Vaccine Advisory Committee, Kimberly Thompson, ScD, Orlando, Florida; Pediatric Infectious Diseases Society, Sean O’Leary, MD,

Denver, Colorado; Pediatric Infectious Diseases Society Alternate, Mark Sawyer, MD, San Diego, California; Pharmaceutical Research and Manufacturers

of America, David Johnson, Swiftwater, Pennsylvania; Society for Adolescent Health and Medicine, Amy Middleman, MD, Houston, Texas; Society for

Healthcare Epidemiology of America, David J. Weber, MD, University of North Carolina, Chapel Hill, North Carolina.

The ACIP Hepatitis Work Group

Membership as of September 16, 2016

Chair: Arthur Reingold, MD, University of California, Berkeley School of Public Health, Berkeley, California

Members: Natali Aziz, MD, MD, Stanford University School of Medicine, Stanford, California; Sharon Balter, MD, New York City Department of Health

and Mental Hygiene, New York, New York; Elizabeth Barnett, MD, Boston University School of Medicine, Boston, Massachusetts; Kathleen Harriman,

PhD, California Department of Public Health, Richmond, California; Susan Even, MD, University of Missouri, Columbia, Missouri; Christine Finley,

Vermont Department of Health, Burlington, Vermont; Robert Frenck, MD, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio; Kathleen

Harriman, PhD, California Department of Public Health, Richmond, California; Susan M. Lett, MD, Massachusetts Department of Public Health, Jamaica

Plain, Massachusetts; Marian Major, PhD, Food and Drug Administration, Silver Spring, Maryland; Brian McMahon, MD, Alaska Native Tribal Health

Consortium, Anchorage, Alaska; Amy Middleman, MD, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; David A. Nace, MD,

University of Pittsburgh, Pittsburgh, Pennsylvania; Gregory Poland, MD, Mayo Clinic, Rochester, Minnesota; Pamela Rockwell, DO, University of Michigan,

Ann Arbor, Michigan; José Romero, MD, University of Arkansas for Medical Sciences, Little Rock, Arkansas; Brenna Simons-Petrusa, PhD, Alaska Native

Tribal Health Consortium, Anchorage, Alaska; Ann Thomas, MD, Oregon Health Authority, Portland, Oregon; David J. Weber, MD, University of North

Carolina, Chapel Hill, North Carolina, Matthew Zahn, MD, Children’s Hospital of Orange County, Orange, California; Jennifer Zipprich, PhD, California

Department of Public Health, Richmond, California.

Contributors (CDC): Carolyn Bridges, MD, Maria Cano, MD, Melissa Collier, MD, Mona Doshani, MD, Mark Gershman, MD, Penina Haber, MPH,

Aaron Harris, MD, Beth Hibbs, MPH, Scott Holmberg, MD, Ruth Jiles, PhD, David Kim, MD, Alaya Koneru, MPH, Noele Nelson, MD, PhD, Sarah

Schillie, MD, Philip Spradling, MD, Claudia Vellozzi, MD, John Ward, MD, Tureka Watson, MS, Donna L. Weaver, MN, Matthew Wise, PhD.

Recommendations and Reports

MMWR / January 12, 2018 / Vol. 67 / No. 1 31

US Department of Health and Human Services/Centers for Disease Control and Prevention

CDC Adoption of ACIP Recommendations

Recommendations for the routine use of vaccines in children, adolescents, and adults are developed by the Advisory Committee on Immunization Practices

(ACIP). ACIP is chartered as a federal advisory committee to provide expert external advice and guidance to the Director of CDC on use of vaccines and related

agents for the control of vaccine-preventable diseases in the civilian population of the United States. Clinical recommendations for routine use of vaccines

are harmonized to the greatest extent possible with recommendations made by others (e.g., the American Academy of Pediatrics, the American Academy of

Family Physicians, the American College of Obstetricians and Gynecologists, and the American College of Physicians).

ACIP recommendations adopted by the CDC Director become agency guidelines on the date published in MMWR. The accompanying recommendations

that summarize the ACIP findings and conclusions were drafted based on the recommendations and revised based on feedback from ACIP voting members.

The CDC Director approved these recommendations prior to publication. Opinions of individual members of ACIP might differ to some extent from the

recommendations in this report as these recommendations are the position of CDC based on the ACIP recommendations to the CDC Director. Additional

information regarding ACIP is available at https://www.cdc.gov/vaccines/acip.

ISSN: 1057-5987 (Print)

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