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Viral hepatitis is a term commonly used for several diseases 

that are clinically similar but etiologically and epidemiologically 

distinct. Hepatitis A (formerly called “infectious hepatitis”) 

and hepatitis B (formerly called “serum hepatitis”) have been 

recognized as separate entities since the early 1940s and can 

be diagnosed with specific serologic tests. Hepatitis D, or Delta 

hepatitis, is an infection dependent on the hepatitis B virus 

(HBV). It may occur as a coinfection with acute HBV infection or 

as superinfection of an HBV carrier.

Epidemic jaundice was described by Hippocrates in the 5th 

century BCE. The first recorded cases of serum hepatitis are 

thought to be those that followed the administration of 

smallpox vaccine containing human lymph to shipyard workers 

in Germany in 1883. In the early and middle parts of the 20th 

century, serum hepatitis was repeatedly observed following the 

use of contaminated needles and syringes. The role of blood 

as a vehicle for virus transmission was further emphasized in 

1943, when Paul Beeson described jaundice that had occurred 

in seven recipients of blood transfusions. Australia antigen, later 

called hepatitis B surface antigen (HBsAg), was first described 

in 1965, and the Dane particle (complete hepatitis B virion) was 

identified in 1970. Identification of serologic markers for HBV 

infection followed and helped to clarify the natural history of 

the disease. Ultimately, HBsAg, the surface protein of HBV, was 

manufactured in quantity and now comprises the immunogen 

in highly effective vaccines for prevention of HBV infection.

A plasma-derived Hepatitis B (HepB) vaccine was first licensed 

for use in the United States in 1981. The vaccine was safe 

and effective but was not well accepted, possibly because of 

unsubstantiated fears of transmission of live HBV and other 

blood-borne pathogens. Recombinant HepB vaccines replaced 

plasma-derived HepB vaccines beginning in 1986. Plasmaderived HepB vaccines are no longer used in the United States. 

Hepatitis B Virus (HBV) 

HBV is a small, double-stranded DNA virus in the family 

Hepadnaviridae. 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). At least 

one serologic marker is present during the different phases 

of infection. Hepatitis B e antigen (HBeAg) can be detected in 

persons with acute or chronic HBV infection; the presence of 

HBeAg correlates with viral replication, high viral levels of HBV 

DNA, and high infectivity; antibody to HBeAg (anti-HBe) usually 

correlates with the decrease of replicating virus, although 

reversion to HBeAg positivity can occur.

Penina Haber, MPH and Sarah Schillie, MD, MPH, MBA

Hepatitis B

● Epidemic jaundice described by

Hippocrates in 5th century BCE

● First recorded cases in 1883

following administration of

smallpox vaccine containing

human lymph

● Transmission via blood further

emphasized in 1943

● HBsAg first described in 1965

● Plasma-derived HepB vaccine

licensed in 1981 replaced in

1986 with recombinant

HepB vaccines

Hepatitis B Virus

● Hepadnaviridae family (DNA)

● Multiple serologic markers

for infection

● Classified by serologic

subtype and genotype, which

vary geographically

● Infectious for at least 7 days

on surfaces

https://www.cdc.gov/vaccines/pubs/pinkbook/hepb.html Aug 2021
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HBV has been classified by two separate systems: serologic 

subtype and genotype. Nine serologic subtypes based on 

the heterogeneity of HBsAg have been described. Ten HBV 

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

serotypes and genotypes vary geographically. HBV genotypes 

are associated with the modes of HBV transmission (vertical 

versus horizontal) and with the risk of certain outcomes of 

chronic infection, such as cirrhosis and hepatocellular carcinoma 

(HCC). For example, in Alaska, HBV genotype F is associated 

with HCC in children as well as adults younger than age 30 

years, while in Asia as well as Alaska, HBV genotype C has been 

associated with a significantly higher risk of HCC than other 

genotypes. Infection or immunization with one HBV genotype 

generally confers immunity to all genotypes.

HBV remains infectious for at least 7 days on environmental 

surfaces and is transmissible in the absence of visible blood. 

Pathogenesis 

HBV is transmitted by parenteral or mucosal exposure to HBsAgpositive body fluids from persons who have acute or chronic 

HBV infection. It replicates in hepatocytes through a unique 

reverse transcription process.

Clinical Features

The clinical course of acute hepatitis B is indistinguishable from 

that of other types of acute viral hepatitis. The incubation period 

typically ranges from 60 to 90 days. Clinical signs and symptoms 

occur more often in adults than in infants or children; infants 

and young children usually are asymptomatic. Approximately 

50% of adults who have acute infections are asymptomatic. 

The preicteric, or prodromal, phase from initial symptoms to 

onset of jaundice usually lasts 3 to 10 days. It is nonspecific 

and is characterized by abrupt onset of fever, malaise, 

anorexia, nausea, abdominal discomfort, and dark urine 

beginning 1 to 2 days before the onset of jaundice. The 

icteric phase is variable but usually lasts from 1 to 3 weeks 

and is characterized by jaundice, light or gray stools, hepatic 

tenderness, and hepatomegaly (splenomegaly is less 

common). During convalescence, malaise and fatigue may 

persist for weeks or months, while jaundice, anorexia, and 

other symptoms disappear.

Most acute HBV infections in adults result in complete recovery 

with elimination of HBsAg from the blood and the production 

of anti-HBs, creating immunity to future infection. In contrast, 

as many as 90% of HBV infections in infants progress to 

chronic infection. Perinatal transmission from mother to 

infant at birth (vertical transmission) is highly efficient. Prior 

to the widespread availability of postexposure prophylaxis, 

Hepatitis B Pathogenesis

● Transmission by parenteral or

mucosal exposure

● Replicates in hepatocytes

● Unique reverse

transcription replication

Hepatitis B Clinical Features

● Incubation period 60 to 90 days

● Clinical signs and symptoms

more common in adults

● Prodromal phase lasts 3 to 10

days; abrupt onset of fever,

malaise, anorexia, nausea,

abdominal discomfort, and dark

urine before jaundice

● Icteric phase lasts 1 to 3

weeks; jaundice, light or gray

stools, hepatic tenderness,

hepatomegaly

● Convalescent phase lasts weeks

to months; malaise and fatigue

persist while jaundice, anorexia,

and other symptoms disappear

● Most adults recover while

most infants progress to

chronic infection
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the proportion of infants born to HBsAg-positive women that 

acquired HBV infection was approximately 30% for those born 

to HBeAg-negative mothers and 85% for those born to HBeAgpositive mothers. With postexposure prophylaxis, comprised 

of HepB vaccine and hepatitis B immune globulin (HBIG) at 

birth, followed by completion of the HepB vaccine series, 0.7% 

through 1.1% of infants develop infection; infants born to 

mothers with high viral loads are at greatest risk for infection 

despite receipt of HepB vaccine and HBIG. 

Complications

While most acute HBV infections in adults result in complete 

recovery, fulminant hepatitis occurs in about 1% to 2% of 

acutely infected persons. Although the consequences of acute 

HBV infection can be severe, most of the serious complications 

associated with HBV infection are due to chronic infection.

Chronic HBV Infection

The proportion of persons with acute HBV infection who 

progress to chronic infection varies with age and immune 

status. As many as 90% of infants who acquire HBV infection 

from their mothers at birth or in infancy become chronically 

infected. Of children who become infected with HBV between 

age 1 and 5 years, 30% to 50% become chronically infected. 

The risk of acquiring chronic HBV infection when infected 

during adulthood is approximately 5%. Acute HBV progresses to 

chronic HBV in approximately 40% of hemodialysis patients and 

up to 20% of patients with immune deficiencies.

Persons with chronic infection are often asymptomatic and may 

not be aware they are infected; however, they are capable of 

infecting others and have been referred to as carriers. Chronic 

infection is responsible for most HBV-related morbidity and 

mortality, including chronic hepatitis, cirrhosis, liver failure, and 

HCC. 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. 

An estimated 257 million persons worldwide are living with 

HBV infection. HBV infection is an established cause of acute 

and chronic hepatitis and cirrhosis. The frequency of infection 

and patterns of transmission vary in different parts of the 

world. In China, Southeast Asia, most of Africa, most Pacific 

Islands, parts of the Middle East, and the Amazon Basin, 8% 

to 15% of the population has chronic HBV infection. In these 

high-prevalence areas, most infections are acquired at birth 

or during early childhood when the risk of developing chronic 

infections is greatest. In these areas, because most infections 

are asymptomatic, very little acute disease related to HBV 

occurs, but rates of chronic liver disease and liver cancer among 

adults are very high. In the United States, Western Europe, and 

Hepatitis B Complications

● Fulminant hepatitis in about 1% 

to 2% of acutely infected adults

Chronic Hepatitis B Virus 

Infection (HBV)

● Proportion of persons with 

acute HBV that progress to 

chronic HBV

■ As many as 90% of infants

■ 30% to 50% of children 

between age 1 and 5 years

■ 5% of adults

● Often asymptomatic

● Responsible for most 

HBV-related morbidity 

and mortality

● 25% of persons infected as 

children and 15% of persons 

infected as adults will 

die prematurely
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Australia, HBV infection is a disease of low endemicity. Infection 

occurs primarily during adulthood, and only 0.1% to 0.5% of the 

population has chronic HBV infection. 

Laboratory Testing

Diagnosis is based on clinical, laboratory, and epidemiologic 

findings. HBV infection cannot be differentiated based on 

clinical symptoms alone, and definitive diagnosis depends 

on the results of serologic testing. Serologic markers of HBV 

infection vary depending on whether the infection is acute 

or chronic.

HBsAg is the most used test for diagnosing acute HBV 

infections or detecting carriers. HBsAg can be detected as early 

as 1 or 2 weeks and as late as 11 or 12 weeks after exposure 

to HBV. The presence of HBsAg indicates that a person is 

infectious, regardless of whether the infection is acute or 

chronic. Transient HBsAg positivity can occur up to 18 days 

following vaccination (up to 52 days among hemodialysis 

patients) and is clinically insignificant.

Anti-HBs is a protective, neutralizing antibody. The presence 

of anti-HBs following acute HBV infection generally indicates 

recovery and immunity against reinfection. Anti-HBs can also be 

acquired as an immune response to HepB vaccine or passively 

transferred by administration of HBIG. The level of anti-HBs 

considered as a protective level of immunity when following 

a complete vaccination series is 10 mIU/mL. 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.

Anti-HBc develops in all HBV infections, appears shortly after 

HBsAg in acute disease, and indicates HBV infection at some 

undefined time in the past. Anti-HBc generally persists for life. 

Persons who are HBsAg-negative and anti-HBc-positive can 

experience reactivation of infection during chemotherapy or 

immunosuppressive therapy, with reappearance of HBsAg.

IgM anti-HBc appears in persons with acute disease about the 

time of illness onset and indicates recent infection with HBV. 

IgM anti-HBc is generally detectable 4 to 6 months after onset 

of illness and is the best serologic marker of acute HBV infection. 

HBeAg is a marker that is associated with a high number 

of infective HBV particles in the serum and a higher risk of 

infectivity. Anti-HBe correlates with a reduction of replicating 

virus and lower infectivity, although reversion to HBeAg 

positivity can occur.

HBV DNA assays are used to monitor response to treatment, 

assess the likelihood of perinatal HBV transmission, and detect 

the presence of occult HBV infection (i.e., infection in someone 
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10

who tests HBsAg-negative). In resource-limited settings, HBeAg 

may replace the use of HBV DNA for some purposes, e.g., 

assessment of perinatal HBV transmission risk. 

Medical Management

There is no specific therapy for acute HBV infection. Treatment 

is supportive. Guidelines for management of chronic HBV 

infection in children and adults, including disease monitoring 

and antiviral therapy, are available from the American 

Association for the Study of Liver Diseases (AASLD, https://www.

AASLD.org). Antiviral therapy, while not curative, can reduce the 

level of HBV DNA and quiet liver inflammation. Following the 

AASLD Guidelines/Guidance, antiviral therapy should generally 

be initiated in patients with chronic HBV infection who have 

high levels of virus and active liver inflammation characterized 

by elevated liver transaminase levels. These persons are at high 

risk for liver-related morbidity.

AASLD suggests antiviral therapy to reduce perinatal HBV 

transmission when maternal HBV DNA is greater than 200,000 

IU/mL starting in the third trimester. Maternal therapy is 

generally discontinued at birth to 3 months postpartum.

Persons with acute or chronic HBV infections should prevent 

their blood and other potentially infective body fluids from 

contacting other persons. They should not donate blood or 

share toothbrushes or razors with household members. In 

health care settings, patients with HBV infection should be 

managed with standard precautions.

Epidemiology

Occurrence

HBV infection occurs worldwide. The frequency of infection 

varies in different parts of the world but is more common in 

some countries in Asia, Africa, South America, and the Caribbean.

Reservoir

HBV infection affects humans. Additionally, some primates 

(chimpanzee, gorilla, orangutan, gibbon) in Africa and Southeast 

Asia are infected with HBV.

Transmission

HBV is transmitted by parenteral or mucosal exposure to 

HBsAg-positive body fluids from persons who have acute or 

chronic HBV infection. The highest concentrations of virus are 

in blood and serous fluids; lower titers are found in other fluids, 

such as saliva, tears, urine, and semen. Semen is a vehicle for 

sexual transmission and saliva can be a vehicle of transmission 

through bites; other types of exposure (e.g., to saliva through 

kissing) are unlikely modes of transmission. HBsAg is also found 

Hepatitis B Epidemiology

● Reservoir

■ Human 

■ Some primates

● Transmission

■ Body fluids (highest 

concentration in blood 

and serous fluids)

● Temporal Pattern

■ No temporal pattern

● Communicability

■ Persons with acute or 

chronic HBV infection are 

infectious any time HBsAg 

present in blood

■ Persons with acute HBV 

infection can have HBsAg in 

blood 1–2 months before and 

after onset of symptoms
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in other body fluids (e.g., breast milk, bile, feces, nasopharyngeal 

washings, and sweat). However, most body fluids are not 

efficient vehicles of transmission (unless they contain blood) 

because they contain low quantities of infectious HBV. 

In the United States, the most important routes of transmission 

are injection-drug use, perinatal, and sexual contact with 

an infected person. Fecal-oral transmission does not appear 

to occur. However, transmission occurs among men who 

have sex with men (MSM), possibly via contamination from 

asymptomatic rectal mucosal lesions. In the 2000s and 2010s, 

outbreaks of hepatitis B occurred in long-term care facilities 

(e.g., assisted living facilities and nursing homes) as the result of 

inadequate infection control practices related to blood glucose 

monitoring. Transmission occurs in households from persons 

who have immigrated from endemic areas and who have 

chronic HBV infection.

Temporal Pattern

HBV infection is reported throughout the year. There is no 

known temporal pattern.

Communicability

Persons with either acute or chronic HBV infection should be 

considered infectious any time that HBsAg is present in the 

blood. When symptoms are present in persons with acute HBV 

infection, HBsAg can be found in blood and body fluids for 1 to 

2 months before and after the onset of symptoms.

Direct, percutaneous inoculation of HBV by needles during 

injection-drug use is an important mode of transmission. 

Breaks in the skin without overt needle puncture, such as fresh, 

cutaneous scratches, abrasions, burns, or other lesions, may also 

serve as routes for entry. Exposures such as transfusion of blood 

or blood products, hemodialysis, use of meters and lancets for 

blood glucose monitoring, insulin pens, and needle-stick or 

other sharps injuries sustained by health care personnel (HCP) 

have all resulted in HBV transmission. Outbreaks have been 

reported among patients in dialysis centers in many countries 

through failure to adhere to recommended infection control 

practices. Past outbreaks have been traced to tattoo parlors, 

acupuncturists, and barbers. 

Secular Trends in the United States

Hepatitis B became nationally notifiable as a distinct entity 

during the 1970s after serologic tests to differentiate different 

types of hepatitis became widely available.

In 2018, a total of 3,322 cases of acute hepatitis B were reported 

to CDC, for an overall incidence rate of 1.0 cases per 100,000 

population. After adjusting for under-ascertainment and 

Hepatitis B Secular Trends 

in the United States

● Acute HBV infection

■ Before vaccine, about 

9.6 per 100,000 cases

■ Following vaccine, about 

1 per 100,000 cases in 2018 

(~90% decrease) 

■ During 2009 through 2013, 

KY, TN, and WV experienced 

114% increase associated with 

injection-drug use

■ Incidence greatest for 

persons 40 through 49 years 

and lowest for persons 

19 years or younger

● Chronic HBV infection

■ Estimated 850,000 to 2.2 

million persons infected in the 

U.S.; most immigrated from 

endemic countries
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under-reporting, an estimated 21,600 acute hepatitis B cases 

occurred in 2018. The rate of reported acute HBV infections 

declined approximately 90% since recommendations for 

HepB vaccination were first issued, from 9.6 cases per 100,000 

population in 1982 to 1.0 cases per 100,000 population in 2018.

During 2009 through 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. Incidence is greatest for persons age 40 

through 49 years (2.5 per 100,000 population); persons age 

19 years or younger have the lowest incidence (0.02 cases per 

100,000 population), likely a result of routine infant vaccination. 

Although HBV infection is uncommon among adults in the 

general population (the lifetime risk of infection is less than 

20%), it is highly prevalent in certain groups. Generally, the 

highest risk for HBV infection is associated with lifestyles, 

occupations, or environments in which contact with blood 

from infected persons is frequent. Chronic HBV infection 

has been identified in 3.5% to 20.0% of persons who inject 

drugs (PWID) in a variety of settings, and 22.6% of PWID have 

evidence of past infection. 

An estimated 850,000 to 2.2 million persons in the United 

States are chronically infected with HBV. Most persons in the 

United States with chronic HBV infection have immigrated from 

endemic countries in the world. While screening persons who 

immigrate for HBsAg, anti-HBc and anti-HBs is recommended, 

it is not enforced. Therefore, clinicians and public health 

workers should screen all persons born in countries with high 

endemicity of HBV virus.

Among children born during 2015–2016, 75.0% received the 

HepB vaccine birth dose administered from birth through 

age 3 days. This was an increase from 71.8% for children born 

during 2013–2014. By age 24 months, 91.0% of children had 

received at least 3 doses of HepB vaccine. In 2017, 25.8% of 

adults age 19 years or older had received at least 3 doses 

of HepB vaccine; the coverage was 34.3% and 16.6% for 

adults age 19 through 49 years and age 50 years or older, 

respectively. Among HCP with direct patient contact, 70% had 

received at least 3 doses of HepB vaccine.

Hepatitis B Prevention Strategies

HepB vaccination is the mainstay of hepatitis B prevention 

efforts. A comprehensive strategy to eliminate HBV 

transmission includes universal vaccination of infants 

beginning at birth, routine vaccination of previously 

unvaccinated children less than age 19 years, and vaccination 

of adults at risk for HBV infection, including those requesting 
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protection from HBV without acknowledgement of a specific 

risk factor. It also includes universal testing of pregnant 

women for HBsAg to identify newborns who require 

immunoprophylaxis for prevention of perinatal infection and 

to pregnant women who can benefit from antiviral therapy to 

reduce perinatal transmission.

Hepatitis B Vaccine

The first recombinant HepB vaccine, Recombivax HB, was 

licensed in the United States in 1986. A second recombinant 

vaccine, Engerix-B, was licensed in 1989. Recombivax HB and 

Engerix-B are available in both pediatric and adult formulations. 

A third recombinant vaccine with a novel adjuvant, Heplisav-B, 

was licensed in 2017 for use in adults age 18 years or older. HBV 

infection cannot result from use of the recombinant vaccine 

since no potentially infectious viral DNA or complete viral 

particles are produced in the recombinant system. 

There are two combination vaccines that contain HepB 

vaccine. DTaP-HepB-IPV (Pediarix) is licensed for children age 

6 weeks through 6 years. HepA-HepB (Twinrix) is licensed for 

persons age 18 years or older. A third combination vaccine, 

DTaP-IPV-Hib-HepB (Vaxelis), is licensed in the United States. 

Characteristics

Recombinant HepB vaccine is produced by inserting a plasmid 

containing the gene for HBsAg into yeast (Saccharomyces 

cerevisiae or Hansenula polymorpha); HepB vaccines contain 

yeast protein. HepB vaccines are administered by intramuscular 

injection. Each dose of HepB vaccine contains aluminum as an 

adjuvant or, for Heplisav-B, a small synthetic immunostimulatory 

oligodeoxynucleotide 1018 adjuvant. Each dose of DTaPHepB-IPV contains antibiotics neomycin and polymyxin B; each 

dose of DTaP-IPV-Hib-HepB contains neomycin, polymyxin B, 

and streptomycin; each dose of HepA-HepB contains neomycin. 

HepB vaccines contain no preservative. Presentations of 

HepB vaccines contain latex rubber. Specific ingredients in 

combination vaccines containing HepB vaccine differ.

Recombivax HB and Engerix-B are available in both pediatric 

and adult formulations and are typically administered as a 

3-dose series on a 0, 1, 6 month schedule. Although their 

antigen content differs, the two vaccines are interchangeable 

except for a 2-dose series for adolescents age 11 through 15 

years, for which only Recombivax HB is approved. Heplisav-B is 

administered as a 2-dose series on a 0, 1 month schedule and is 

approved for persons age 18 years or older. 

Hepatitis B Vaccine Characteristics

● Administered by 

intramuscular injection

● Contain yeast protein

● Contain aluminum adjuvant 

(Engerix-B and Recombivax 

HB) or synthetic adjuvant 

(Heplisav-B)

● Some presentations 

contain latex

● Ingredients in combination 

vaccines differ; all 

contain antibiotics

Hepatitis B Vaccines

● DTaP-HepB-IPV (Pediarix)

● DTaP-IPV-Hib-HepB (Vaxelis)

● HepA-HepB (Twinrix)

● HepB (Engerix-B, Heplisav-B, 

and Recombivax HB)
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Vaccination Schedule and Use

Infants and Children

HepB vaccination is recommended for all medically stable 

infants weighing at least 2,000 grams within 24 hours of birth. 

Only single-component vaccine should be used for the birth 

dose and doses administered before age 6 weeks. The usual 

schedule is 0, 1 through 2, and 6 through 18 months. 

All pregnant women found to be HBsAg-positive should have 

their sera tested for HBV DNA. If HBV DNA levels are greater than 

200,000 IU/mL, Tenofovir (preferable) or lamivudine should be 

administered to the pregnant woman starting at the beginning 

of the third trimester and continued one to three months after 

birth. Infants born to mothers who are HBsAg-positive should 

receive the HepB vaccine birth dose and HBIG within 12 hours 

of birth. HepB vaccine and HBIG should be administered in 

separate limbs. For infants weighing less than 2,000 grams, the 

birth dose should not be counted as part of the vaccine series 

because of potentially reduced immunogenicity; 3 additional 

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

beginning when the infant reaches age 1 month. Infants whose 

mothers are HBsAg-positive should receive the last dose by age 

6 months but not before age 24 weeks.

Infants born to mothers whose HBsAg status is unknown 

should receive the HepB birth dose within 12 hours of birth. 

Infants weighing less than 2,000 grams should also receive HBIG 

within 12 hours of birth. The mother’s HBsAg status should be 

assessed as soon as possible. If the mother is determined to be 

HBsAg-positive, infants weighing at least 2,000 grams should 

also receive HBIG as soon as possible but no later than age 7 

days. As with infants born to HBsAg-positive mothers, for infants 

weighing less than 2,000 grams, the birth dose should not be 

counted as part of the vaccine series because of potentially 

reduced immunogenicity; 3 additional doses of vaccine (for a 

total of 4 doses) should be administered beginning when the 

infant reaches age 1 month. Infants with mothers whose HBsAg 

status is unknown should receive the last dose by age 6 months 

but not before age 24 weeks.

Hepatitis B Vaccination Schedule 

● Infants: See Hepatitis B vaccine 

schedule for infants

● Adolescents: All children and 

adolescents through age 18 

years not previously vaccinated 

■ 3-dose series at 0, 1, 6 months

■ Adolescents age 11 through 

15 years may use 2-dose series 

of Recombivax HB separated 

by 4 to 6 months

● Adults: All unvaccinated 

adults at risk for or requesting 

protection from HBV infection 

■ 2-dose series at 0 and 1 

month (Heplisav-B) or 

3-dose series at 0, 1 and 

6 months (Engerix-B and 

Recombivax HB)

■ 3-dose series at 0, 1 and 6 

months (Twinrix)

■ 3-dose series with doses at 

0, 7, 21–30 days, and booster 

12 months after dose 1 

(Twinrix, accelerated)
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Hepatitis B

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Preterm infants weighing less than 2,000 grams have a 

decreased response to HepB vaccine administered before 1 

month of age. However, by chronologic age 1-month preterm 

infants, regardless of initial birth weight or gestational age, are 

as likely to respond as adequately as full-term infants. Preterm 

infants of low birth weight whose mothers are HBsAg-negative 

can receive the first dose of HepB vaccine at chronologic age 

1 month. Preterm infants discharged from the hospital before 

chronologic age 1 month can receive HepB vaccine at discharge 

if they are medically stable and have gained weight consistently, 

even if they are less than 2,000 grams. 

The third HepB dose must be administered at least 8 weeks after 

the second dose, and at least 16 weeks after the first dose. The 

minimum interval between the first and second dose is 4 weeks.

Hepatitis B vaccine schedules for infants (≥2,000 g birthweight), by maternal HBsAg status

Maternal HBsAg Status Single-antigen 

vaccine dose

Single-antigen vaccine 

age indications

Single-antigen + 

combination 

vaccine† dose

Single-antigen + 

combination vaccine†

age indications

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

N/A N/A 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

N/A N/A 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

N/A N/A 4 6 mos¶

* 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 and Vaxelis 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).
Hepatitis B

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Hepatitis B vaccine schedules for infants (<2,000 g birthweight), by maternal HBsAg status

Maternal HBsAg Status Single-antigen 

vaccine dose

Single-antigen vaccine 

age indications

Single-antigen + 

combination 

vaccine† dose

Single-antigen + 

combination vaccine†

age indications

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¶ 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¶ 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

N/A N/A 4 6 mos¶

† Pediarix and Vaxelis 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).

DTaP-HepB-IPV (Pediarix)

DTaP-HepB-IPV vaccine is approved for use as a 3-dose series 

for children age 6 weeks through 6 years. It is administered to 

infants at age 2, 4, and 6 months. The minimum intervals for 

DTaP-HepB-IPV vaccine are determined by the DTaP component. 

The 3 doses must be separated by at least 4 weeks between 

doses. Because the minimum age for the first dose of DTaPHepB-IPV vaccine is 6 weeks, this vaccine cannot be used for 

the birth dose of HepB vaccine. The final dose of DTaP-HepB-IPV 

vaccine should be administered at age 24 weeks or older, the 

minimum age for completion of the HepB vaccine series. When 

DTaP-HepB-IPV vaccine is used to provide 3 doses at age 2, 4, 

and 6 months (based on the DTaP and IPV schedules), this will 

result in a 4-dose HepB vaccine series, which is acceptable.

DTaP-IPV-Hib-HepB (Vaxelis)

DTaP-IPV-Hib-HepB is approved for use as a 3-dose series 

for children age 6 weeks through 4 years. It is administered 

to infants at age 2, 4, and 6 months. The minimum intervals 

for DTaP-IPV-Hib-HepB vaccine are determined by the DTaP 

component. The 3 doses must be separated by at least 4 weeks 

between doses. Because the minimum age for the first dose of 

DTaP-IPV-Hib-HepB vaccine is 6 weeks, this vaccine cannot be 

used for the birth dose of HepB vaccine. The final dose of DTaPIPV-Hib-HepB vaccine should be administered at age 24 weeks 
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or older, the minimum age for completion of the HepB vaccine 

series. When DTaP-IPV-Hib-HepB vaccine is used to provide 3 

doses at age 2, 4, and 6 months (based on the DTaP and IPV 

schedules), this will result in a 4-dose HepB vaccine series, 

which is acceptable.

Adolescents

Routine HepB vaccination is recommended for all children and 

adolescents through age 18 years. All children not previously 

vaccinated with HepB vaccine should be vaccinated. 

An alternative HepB vaccination schedule for adolescents age 

11 through 15 years consists of 2 adult doses of Recombivax 

HB separated by 4 to 6 months. The 2-dose series should be 

completed by the 16th birthday. 

Adults

HepB vaccine is recommended for all unvaccinated adults at risk 

for HBV infection and for all adults requesting protection from 

HBV infection. Acknowledgment of a specific risk factor is not a 

requirement for vaccination. 

Adults recommended for HepB vaccination include: • Persons at risk for infection by sexual exposure, including 

sex partners of HBsAg-positive persons, persons with more 

than one sex partner during the previous 6 months, persons 

seeking evaluation or treatment for a sexually transmitted 

infection (STI), and MSM

• Household contacts of persons who are HBsAg-positive. 

They should be screened first for HBsAg, anti-HBc 

and anti-HBs.

• Persons at risk for infection by percutaneous or mucosal 

exposure to blood, including current or recent PWID, 

household contacts of HBsAg-positive persons, residents 

and staff of facilities for developmentally disabled persons, 

health care and public safety workers with risk for exposure 

to blood or blood-contaminated body fluids

• Persons with end-stage renal disease, including predialysis, 

hemodialysis, peritoneal dialysis, and home dialysis patients

• Persons with diabetes age 19 through 59 years; persons 

with diabetes age 60 years or older at the discretion of the 

treating clinician 

• Persons with hepatitis C infection or chronic liver disease, 

including those 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
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• Persons traveling internationally to regions with high or 

intermediate levels (HBsAg prevalence of 2% or higher) of 

endemic HBV infection, including those who may engage in 

high-risk behaviors or provide health care while traveling

• Persons with human immunodeficiency virus (HIV) infection

• Persons who are incarcerated

• All other persons seeking protection from HBV infection

In settings in which a high proportion of adults have risks for 

HBV infection (e.g., STI/HIV testing and treatment facilities, 

substance use disorder treatment and prevention settings, 

health care settings targeting services to PWID or MSM, and 

correctional facilities), ACIP recommends HepB vaccination for 

all unvaccinated adults. In other primary care and specialty 

medical settings in which adults at risk for HBV infection receive 

care, health care providers should inform all patients about 

the health benefits of vaccination, risks for HBV infection, and 

persons for whom vaccination is recommended, and should 

vaccinate any adults who report risks for HBV infection or 

request protection from HBV infection. 

Heplisav-B

Heplisav-B is approved for use in persons age 18 years or older. 

The schedule is 2 doses separated by 1 month. Even though 

Heplisav-B cannot be combined with a different HepB vaccine 

(e.g., Engerix-B, Recombivax HB, Twinrix) to complete a series, 

any 2 Heplisav-B doses separated by 4 weeks constitutes a 

complete HepB vaccine series, even if other doses of Engerix-B, 

Recombivax HB, or Twinrix, are administered before, after, or 

between the 2 doses of Heplisav-B, regardless of the interval 

between these other vaccines and Heplisav-B.

HepA-HepB (Twinrix)

The vaccine is administered in a 3-dose series on a 0, 1, 6 

months schedule. Dose 1 and dose 3 should be separated by 

at least 6 months. Dose 1 and dose 2 should be separated by 

at least 4 weeks, and dose 2 and dose 3 should be separated 

by at least 5 months. An alternative Twinrix schedule consists 

of doses at 0, 7, 21–30 days, and a booster dose at 12 months 

after the first dose. Because the HepB component of Twinrix 

is equivalent to a standard adult dose of HepB vaccine, 

Twinrix can be administered on a single-antigen HepB vaccine 

schedule; the minimum interval recommendations will be met. 

Single-antigen HepB vaccine can be used to complete a series 

begun with Twinrix or vice versa.

Hepatitis B Vaccine Efficacy

● Over 90% of infants, children, 

adolescents, and healthy adults 

<40 years develop protective 

antibody response following 

complete series

● 80 to 100% effective in 

preventing infection or 

clinical hepatitis following 

complete series

● Larger doses or increased 

number of doses necessary 

for dialysis patients and 

immunocompromised persons

● Booster doses not 

recommended for 

immunocompetent persons
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Immunogenicity and Vaccine Efficacy

More than 90% of infants, children, and adolescents and more 

than 90% of healthy adults younger than age 40 years develop 

a protective antibody response following a complete HepB 

vaccine series. However, there is an age-specific decline in 

immunogenicity. By 60 years, only 75% develop protective 

antibody titers. In adults receiving Heplisav-B, 90 to 100% 

develop adequate antibody after the 2-dose series. 

Infants born to women who are HBsAg-positive are at high 

risk of HBV transmission and chronic HBV infection. HepB 

vaccination and 1 dose of HBIG administered within 24 hours 

after birth are 85% to 95% effective in preventing chronic HBV 

infection. HepB vaccine administered alone beginning within 

24 hours after birth is 70% to 95% effective in preventing 

perinatal HBV infection.

HepB vaccine is 80% to 100% effective in preventing infection 

or clinical hepatitis in those who receive the complete 

vaccine series. Larger vaccine doses (2 to 4 times the normal 

adult dose) or an increased number of doses are required 

to induce protective antibody in most dialysis patients 

age 20 years or older and may also be necessary for other 

immunocompromised persons age 20 years or older. The 

recommended dosage of vaccine differs depending on the age 

of the recipient and type of vaccine.

Available data show that vaccine-induced antibody levels 

decline with time. However, immune memory remains intact 

for more than 30 years following immunization, and both 

adults and children with declining antibody levels are still 

protected against significant HBV infection (i.e., clinical disease, 

HBsAg antigenemia, or significant elevation of liver enzymes). 

Exposure to HBV results in an anamnestic anti-HBs response 

that prevents clinically significant HBV infection. Chronic HBV 

infection has only rarely been documented among those who 

responded to vaccine. 

For adults and children with normal immune status, booster 

doses of vaccine are not recommended. Routine serologic 

testing to assess immune status of persons who are vaccinated 

is not recommended. The need for booster doses after longer 

intervals will continue to be assessed as additional information 

becomes available.

For dialysis patients who did respond to vaccine, the need for 

booster doses should be assessed by annual testing of vaccine 

recipients for antibody levels, and a booster dose should be 

provided when antibody levels decline below 10 mIU/mL.

Seroconversion rates and postvaccination anti-HBs titers are 

similar among adolescents age 11 through 15 years vaccinated 

using the 2 adult-dose Recombivax HB schedule compared to 

those vaccinated using 3 doses.
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Serologic Testing of Vaccine Recipients

Prevaccination Serologic Testing

Vaccination of persons immune to HBV because of current 

or previous infection or HepB vaccination does not increase 

the risk for adverse events. 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 

household, sexual, or needle-sharing contacts of HBsAg-positive 

persons; HIV-positive persons; persons with elevated ALT/ AST 

of unknown etiology; hemodialysis patients; MSM; and past or 

current PWID. 

Serologic testing is not recommended before routine 

vaccination of infants, children, or adolescents.

Postvaccination Serologic Testing

Testing for immunity following vaccination is not recommended 

routinely. However, testing is recommended for persons 

whose subsequent management depends on knowledge of 

their immune status, including infants born to 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), HCP 

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), and sex partners of HBsAg-positive persons.

Testing should be performed 1 to 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 

(greater than or equal to 10 mIU/mL). Persons found to have 

anti-HBs concentrations of greater than or equal to 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. 

Serologic Testing

Prevaccination

● Consists of testing for HBsAg, 

anti-HBs, and anti-HBc

● Recommended for:

■ Household, sexual, or needlesharing contacts of HBsAgpositive persons

■ HIV-positive persons

■ Persons with elevated ALT/

AST of unknown etiology

■ Hemodialysis patients

■ MSM

■ Past or current PWID

Postvaccination

● Not routinely recommended 

● Recommended for:

■ Infants born to HBsAg+ 

women or women with 

unknown HBsAg status

■ HCP and public safety workers

■ Hemodialysis patients

■ HIV-infected persons

■ Other immunocompromised 

persons

■ Sex partners of HBsAg+ 

persons

● Results:

■ Anti-HBs ≥ 10 mIU/mL 

 Immune

■ Anti-HBs < 10 mIU/mL 

 Revaccinate
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Persons found to have anti-HBs concentrations less than 

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 to 

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). 

Infants born to HBsAg-positive women or HBsAg-unknown 

women whose status is not determined should be tested for 

HBsAg and anti-HBs 1 to 2 months after completion of the final 

dose of the HepB vaccine series, at age 9 through 12 months 

(generally at the next well-child visit following completion of 

the HepB vaccine series). If HBsAg is not present and anti-HBs 

antibody is greater than or equal to 10 mIU/mL, children can be 

considered to be protected.

HCP who have contact with blood and body fluids of patients 

who might be infected with HBV, or who are at ongoing risk 

for injuries with sharp instruments or needlesticks, should 

be tested for antibody 1 to 2 months after completion 

of the hepatitis B vaccine series. Increasingly, HCP with 

documentation of routine HepB vaccination received the 

series in infancy or as catch-up vaccination in adolescence 

without postvaccination testing, but they may be tested as a 

condition of employment. Antibody to vaccine antigen wanes 

over time, although protection persists in immunocompetent 

vaccine recipients who responded initially. A negative anti-HBs 

serologic response in HCP who received HepB vaccine in the 

distant past will not distinguish between failure to respond to 

the initial vaccination series (lack of protection) and response 

to the initial vaccination series with subsequent waning of 

antibody (protected). 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 less than10 mIU/mL should receive one or more 

additional doses of HepB vaccine and retesting. 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.
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Vaccine Nonresponse

Several factors have been associated with nonresponse 

to HepB vaccine. These include vaccine factors (e.g., dose, 

schedule, injection site) and host factors (e.g., older age, male 

gender). Older age (40 years and older), male gender, obesity, 

diabetes, smoking, and chronic illness have been independently 

associated with nonresponse to HepB vaccine. Additional 

vaccine doses for persons who receive postvaccination testing 

and who fail to respond to a primary vaccination series 

administered in the deltoid muscle produce adequate response 

in 15% to 25% of these persons after 1 additional dose and in 

30% to 50% after 3 additional doses.

Persons who do not respond to the first series of HepB vaccine 

should complete a second vaccine series. The second vaccine 

series should be given on the usual 0, 1, 6 month schedule. 

HCP and others for whom postvaccination serologic testing 

is recommended should be retested 1 to 2 months after 

completion of the second vaccine series. 

Fewer than 5% of persons receiving 6 doses of HepB vaccine 

administered by the appropriate schedule in the deltoid 

muscle fail to develop detectable anti-HBs antibody. One 

reason for persistent nonresponse to HepB vaccine is chronic 

infection with HBV. Persons who fail to develop detectable 

anti-HBs after 6 doses should be tested for HBsAg and 

anti-HBc. Persons who are found to be HBsAg-positive should 

be counseled accordingly and linked to care with providers 

experienced in the management of chronic HBV infection. 

Persons who fail to respond to two appropriately administered 

series and who are HBsAg-negative should be considered 

susceptible to HBV infection and should be counseled 

regarding precautions to prevent HBV infection. They should 

also be counseled about the need to obtain HBIG prophylaxis 

for exposure to HBsAg-positive blood.

Vaccine Nonresponse

● Persons who do not respond 

to the first HepB series should 

complete a second series on a 

0, 1, 6 month schedule

● Retest anti-HBs 1–2 months 

after completion of 

second series
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Occupational Postexposure Management

After a percutaneous (needle stick, laceration, bite) or 

permucosal exposure that contains or might contain HBV, 

blood should be obtained from the source patient to determine 

their HBsAg status. Management of the exposed HCP depends 

on the HBsAg status of the source and the vaccination and 

anti-HBs response status of the exposed HCP. Recommended 

postexposure prophylaxis is described in the following table.

Postexposure Management of Health Care Personnel after Occupational Exposure to Blood and Body 

Fluids, by Health Care Personnel HepB Vaccination and Response Status

HepB Vaccination 

and Response 

Status

Postexposure 

testing results for 

source patient 

(HBsAg)

Postexposure 

testing results for 

HCP (anti-HBs)

HBIG* 

postexposure 

prophylaxis

Vaccination 

postexposure 

prophylaxis

Postvaccination 

Serologic 

Testing†

Documented 

responder§ after 

complete series 

(3 or more doses)

No action needed No action needed No action needed No action needed No action needed

Documented 

nonresponder¶

after 2 complete 

series

Positive/ unknown ** 2 doses HBIG 

separated by 

1 month

No action needed No action needed

Negative No action needed No action needed No action needed No action needed

Response 

unknown after a 

complete series

Positive/ unknown less than 

10 mIU/mL**

1 dose HBIG Initiate 

revaccination

Yes

Negative less than 

10 mIU/mL

None Initiate 

revaccination

Yes

Any result greater than or 

equal to 10 mIU/mL

No action needed No action needed No action needed

Unvaccinated/

incompletely 

vaccinated or 

vaccine refusers

Positive/ unknown ** 1 dose HBIG Complete 

vaccination

Yes

Negative No action needed None Complete 

vaccination

Yes

*HBIG should be administered intramuscularly as soon as possible after exposure when indicated. The effectiveness of HBIG when 

administered greater than 7 days after percutaneous, mucosal, or nonintact skin exposures is unknown. HBIG and HepB vaccine 

should be administered in separate anatomic injection sites.

†

Should be performed 1 to 2 months after the last dose of the HepB vaccine series (and 4 to 6 months after administration of HBIG 

to avoid detection of passively administered anti-HBs) using a quantitative method that allows detection of the protective concentration of anti-HBs (greater than or equal to 10 mIU/mL).

§

A responder is defined as a person with anti-HBs greater than or equal to 10 mIU/mL after 3 or more doses of HepB vaccine.

¶

A nonresponder is defined as a person with anti-HBs less than 10 mIU/mL after 2 complete series of HepB vaccine.

**HCP who have anti-HBs less than 10 mIU/mL, or who are unvaccinated or incompletely vaccinated, and sustain an exposure to a 

source patient who is HBsAg-positive or has unknown HBsAg status, should undergo baseline testing for HBV infection as soon as 

possible after exposure and follow-up testing approximately 6 months later. Initial baseline tests consist of total anti-HBc; testing at 

approximately 6 months consists of HBsAg and total anti-HBc.

Non-Occupational Exposure 

Persons who have written documentation of a complete 

HepB vaccine series and who did not receive postvaccination 

testing should receive a single vaccine booster dose after 

non-occupational exposure to an HBsAg-positive source. 

Persons who are in the process of being vaccinated but who 

have not completed the vaccine series should complete the 
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vaccine series and receive the appropriate dose of HBIG as soon 

as possible. 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. Unvaccinated 

persons should receive both HBIG and a dose of HepB vaccine 

as soon as possible after exposure (preferably within 24 

hours) and complete the HepB vaccine series according to 

the appropriate schedule. HepB vaccine may be administered 

simultaneously with HBIG in a separate injection site, i.e., 

separate limb.

Contraindications and Precautions 

to Vaccination

As with other vaccines, a history of a severe allergic reaction 

(anaphylaxis) to a vaccine component or following a prior 

dose is a contraindication to further doses. Moderate or severe 

acute illness (with or without fever) in a patient is considered a 

precaution to vaccination, although persons with minor illness 

may be vaccinated. 

In 2011, the Institute of Medicine concluded that the evidence 

convincingly supports a causal relationship between HepB 

vaccine and anaphylaxis in yeast-sensitive persons. HepB 

vaccination is contraindicated for persons with a history of 

hypersensitivity to yeast or any other vaccine component. 

The estimated incidence of anaphylaxis among HepB vaccine 

recipients is 1.1 per million vaccine doses administered. 

Some presentations of HepB vaccines contain latex, which may 

cause allergic reactions.

Vaccination is not contraindicated in persons with a history of 

multiple sclerosis, Guillain-Barré syndrome, autoimmune disease 

(e.g., systemic lupus erythematosis or rheumatoid arthritis) or 

other chronic diseases. 

Contraindications to combination vaccines that contain 

HepB vaccine include the contraindications to the individual 

component vaccines (e.g., DTaP, hepatitis A); specific ingredients 

differ by vaccine.

Vaccination during Pregnancy

Pregnancy is not a contraindication to HepB vaccination. 

Limited data suggest that developing fetuses are not at risk for 

adverse events when HepB vaccine is administered to pregnant 

women. Available vaccines contain noninfectious HBsAg and 

should cause no risk of infection to the fetus.

Pregnant women who are identified as being at risk for HBV 

infection during pregnancy (e.g., persons with more than one 

sex partner during the previous 6 months, persons who have 

Hepatitis B Vaccine 

Contraindications and Precautions

● Contraindication

■ Severe allergic reaction 

to vaccine component or 

following a prior dose

■ History of hypersensitivity 

to yeast

● Precaution

■ Moderate or severe 

acute illness
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been evaluated or treated for an STI, recent or current PWID, or 

persons who have had an HBsAg-positive sex partner) should 

be vaccinated.

Heplisav-B is not recommended in pregnancy, based on a lack 

of available safety data. 

Vaccine Safety

In prelicensure trials, adverse events following HepB vaccination 

were most commonly injection site reactions and mild systemic 

reactions. Commonly reported mild adverse events from 

postmarketing data include pain (3% to 29%), erythema (3%), 

swelling (3%), fever (1% to 6%), and headache (3%). 

In rare instances, other illnesses have been reported after 

HepB vaccination, including Guillain-Barré syndrome, chronic 

fatigue syndrome, neurologic disorders (e.g., leukoencephalitis, 

optic neuritis, and transverse myelitis), rheumatoid arthritis, 

type 1 diabetes, and autoimmune disease. However, no causal 

association between those conditions or any other chronic 

illness and HepB vaccine has been demonstrated. Reviews by 

scientific panels have also found no causal association between 

HepB vaccination and multiple sclerosis.

Reported episodes of alopecia (hair loss) after rechallenge with 

HepB vaccine suggest that vaccination might very rarely trigger 

alopecia. “Rechallenge” in this context means the same adverse 

event occurs twice, each time after sequential doses of vaccine. 

Some cases were transient. However, a population-based study 

found no statistically significant association between alopecia 

and Hep B vaccination.

Vaccine Storage and Handling

HepB vaccine should be maintained at refrigerator temperature 

between 2°C and 8°C (36°F and 46°F). Manufacturer package 

inserts contain additional information. For complete information 

on best practices and recommendations, please refer to CDC’s 

Vaccine Storage and Handling Toolkit, www.cdc.gov/vaccines/

hcp/admin/storage/toolkit/storage-handling-toolkit.pdf.

Surveillance and Reporting of Hepatitis B 

Hepatitis B infection is nationally notifiable in the United 

States. For information on guidance for state and local health 

department staff who are involved in surveillance activities for 

vaccine-preventable diseases, please consult the Manual for the 

Surveillance of Vaccine-Preventable Diseases, www.cdc.gov/

vaccines/pubs/surv-manual/chapters.html. 

Hepatitis B Vaccine Safety

● Pain

■ 3% to 29%

● Erythema

■ 3%

● Swelling

■ 3%

● Fever

■ 1% to 6%

● Headache

■ 3%
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Acknowledgements

The editors would like to acknowledge Maria Cano and Phil 

Spradling for their contributions to this chapter.

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NOTES
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NOTES