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The first descriptions of hepatitis (epidemic jaundice) are 

generally attributed to Hippocrates. Outbreaks of jaundice, 

probably hepatitis A, were reported in the 17th and 18th 

centuries, particularly in association with military campaigns. 

Hepatitis A (formerly called “infectious hepatitis”) was first 

differentiated epidemiologically from hepatitis B, which has 

a longer incubation period, in the 1940s. Development of 

serologic tests allowed definitive diagnosis of hepatitis B. 

In the 1970s, identification of the virus and development of 

serologic tests helped differentiate hepatitis A from other 

types of non-B hepatitis.

In the prevaccine era, the primary methods used for 

preventing hepatitis A were hygienic measures and passive 

protection with immune globulin (IG). Hepatitis A (HepA) 

vaccines were first licensed for use in the United States in 

1995. These vaccines provide long-term protection against 

hepatitis A virus (HAV) infection. The similarities between the 

epidemiology of hepatitis A and poliomyelitis suggest that 

widespread vaccination of appropriate susceptible populations 

with HepA vaccines can substantially lower disease incidence, 

eliminate virus transmission, and ultimately, eliminate HAV 

infection. Prior to 2004, hepatitis A was the most frequently 

reported type of hepatitis in the United States. From 1996, 

when the HepA vaccine was introduced, through 2011, 

hepatitis A cases decreased by over 95%, but re-emerged in 

2016 in the United States due to widespread outbreaks among 

persons reporting drug use and homelessness. In response, 

CDC has been assisting multiple state and local health 

departments with hepatitis A outbreaks.

Hepatitis A Virus

Hepatitis A is caused by infection with HAV, an RNA virus 

that is classified as a picornavirus. It was first isolated in 

1979. Humans are the only natural host, although several 

nonhuman primates have been infected in laboratory 

conditions. Depending on conditions, HAV can be stable in 

the environment for months. The virus is relatively stable at 

low pH levels, moderate temperatures, and frozen temperatures, but can be inactivated by high temperature (185°F 

[85°C] or higher), formalin, and chlorine.

Pathogenesis

HAV is typically acquired through ingestion (through fecal-oral 

transmission) and replicates in the liver. After 10 to 12 days, virus 

is present in blood and is excreted via the biliary system into 

the feces. Peak titers occur during the 2 weeks before onset of 

illness. Although virus is present in serum, its concentration is 

several orders of magnitude less than in feces. Virus excretion 

Monique A Foster, MD MPH; Penina Haber, MPH; Noele P Nelson, MD, PhD, MPH

Hepatitis A

● Descriptions of epidemic

jaundice attributed

to Hippocrates

● Differentiated from hepatitis B

in 1940s

● Serologic tests developed

in 1970s

● Vaccines first licensed in the U.S.

in 1995

Hepatitis A Virus

● Picornavirus (RNA)

● Humans are only natural host

● Stable at low pH

● Inactivated by temperature

of 185°F or higher, formalin,

chlorine

Hepatitis A Pathogenesis

● Fecal-oral transmission

● Viral replication in the liver

● Virus present in blood and feces

10 to 12 days after infection

● Virus excretion may continue

for up to 3 weeks after onset

of symptoms

https://www.cdc.gov/vaccines/pubs/pinkbook/hepa.html Aug 2021
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Hepatitis A

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begins to decline at the onset of clinical illness and decreases 

significantly by 7 to 10 days after onset of symptoms. Most 

infected persons no longer excrete virus in the feces by the third 

week of illness. 

Clinical Features

The incubation period of hepatitis A is approximately 28 

days (range 15 to 50 days). The clinical course of hepatitis A 

is indistinguishable from that of other types of acute viral 

hepatitis. The illness typically has an abrupt onset of fever, 

malaise, anorexia, nausea, abdominal discomfort, dark urine, 

and jaundice. Clinical illness usually does not last longer than 

2 months, although 10% to 15% of persons have prolonged or 

relapsing signs and symptoms for up to 6 months. Virus may be 

excreted during a relapse or prolonged Illness.

The likelihood of symptomatic illness from HAV infection is 

directly related to age. In children younger than age 6 years, 

most (70%) infections are asymptomatic. In older children and 

adults, infection is usually symptomatic, with jaundice occurring 

in more than 70% of patients.

Complications

Severe clinical manifestations of hepatitis A infection are 

rare; however, atypical complications may occur, including 

immunologic, neurologic, hematologic, pancreatic, and renal 

manifestations. Relapsing hepatitis, cholestatic hepatitis A, 

hepatitis A triggering autoimmune hepatitis, subfulminant 

hepatitis, and fulminant hepatitis have also been reported. 

Fulminant hepatitis is the most severe rare complication, with 

mortality estimates up to 80%. Overall case-fatality estimates 

range from 0.3% to 0.6% for all ages and up to 1.8% among 

adults age 50 years or older. During outbreaks concentrated 

in older individuals or higher proportions of individuals with 

comorbidities, case-fatality rates can be significantly higher. 

Vaccination of high-risk groups and other public health 

measures have significantly reduced the overall number of 

hepatitis A cases and fulminant HAV infections. However, 

even nonfatal hepatitis A results in substantial morbidity, with 

associated costs of medical care and work loss.

Laboratory Testing

Hepatitis A cannot be distinguished from other types of viral 

hepatitis on the basis of clinical or epidemiologic features alone. 

Serologic testing is required to confirm the diagnosis. Virtually 

all patients with acute hepatitis A have detectable IgM anti-HAV. 

Acute HAV infection is confirmed during the acute or early 

convalescent phase of infection by the presence of IgM anti-HAV 

in serum. IgM generally becomes detectable 5 to 10 days before 

the onset of symptoms and can persist for up to 6 months.

Hepatitis A Clinical Features

● Incubation period 28 days

(range, 15 to 50 days)

● Symptoms: Abrupt onset of

fever, malaise, anorexia, nausea,

abdominal discomfort, dark

urine, jaundice

● Likelihood of symptomatic

illness directly related to age

● Children generally

asymptomatic, adults

symptomatic
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IgG anti-HAV appears in the convalescent phase of infection, 

remains present in serum for the lifetime of the person, and 

confers enduring protection against disease. The antibody 

test for total anti-HAV measures both IgG anti-HAV and IgM 

anti-HAV. Persons who are total anti-HAV-positive and IgM 

anti-HAV-negative have serologic markers indicating immunity 

consistent with either past infection or vaccination.

Molecular virology methods such as polymerase chain reaction 

(PCR)-based assays can be used to amplify and sequence viral 

genomes. These assays are helpful to investigate commonsource outbreaks of hepatitis A. 

Medical Management

There is no specific treatment for hepatitis A virus infection. 

Treatment and management of HAV infection are supportive.

Epidemiology

Occurrence

Hepatitis A occurs throughout the world. It is highly endemic in 

some areas, particularly Central and South America, Africa, the 

Middle East, Asia, and the Western Pacific. 

Reservoir

Humans are the only natural reservoir of the virus. There are 

no insect or animal vectors. A chronic HAV state has not been 

reported although infections may relapse or be prolonged.

Transmission

HAV infection is acquired primarily by the fecal-oral route 

by either ingestion of contaminated food or water or 

direct contact with an infectious person. Since the virus is 

present in blood during the illness prodrome, HAV has been 

transmitted on rare occasions by blood transfusion as well as 

solid organ transplantation. Although HAV may be present 

in saliva, transmission by saliva has not been demonstrated. 

Waterborne outbreaks are infrequent in the United States 

and are usually associated with sewage-contaminated or 

inadequately treated water.

Temporal Pattern

There is no appreciable seasonal variation in hepatitis A 

incidence. In the prevaccine era, cyclic increases in reported 

acute cases were observed every 10 to 15 years and were 

characterized by large community outbreaks of disease.

Hepatitis A Epidemiology

● Reservoir

■ Human

● Transmission

■ Fecal-oral

● Temporal pattern

■ None

● Communicability

■ Most infectious 1-2 weeks

before onset of illness
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Communicability

Viral shedding persists for 1 to 3 weeks. Infected persons are 

most likely to transmit HAV 1 to 2 weeks before the onset of 

illness, when HAV concentration in stool is highest. The risk then 

decreases and is minimal the week after the onset of symptoms. 

Risk Factors

Groups at increased risk for hepatitis A or its complications 

include international travelers (particularly those with high-risk 

itineraries such as travel to rural areas in high-risk regions 

[Central and South America, Africa, Asia]), recent international 

adoptees from hepatitis A-endemic countries and their 

contacts, men who have sex with men, people experiencing 

homelessness, persons with HIV, and people who use drugs. 

Outbreaks of hepatitis A have also been reported among 

persons working with hepatitis A–infected primates. 

Persons with chronic liver disease are not at increased risk of 

infection but are at increased risk of developing fulminant 

hepatitis A if infected. 

Persons with clotting factor disorders may be at increased risk 

of hepatitis A because of administration of solvent/detergenttreated factor VIII and IX concentrates; however, secondary virus 

reduction steps, common use of recombinant clotting factor 

concentrates, and screening of plasma for HAV has greatly 

reduced the risk of HAV transmission from clotting factors to the 

same as that among the general population.

Persons with occupational risk include only those who 

work with hepatitis A–infected nonhuman primates or with 

clinical or nonclinical material containing hepatitis A virus 

in a research laboratory setting. Food handlers are not at 

increased risk for hepatitis A because of their occupation, 

and secondary transmission from food handlers is rare. 

Health care personnel do not have an increased incidence 

of HAV infections, and nosocomial HAV transmission is rare. 

Nonetheless, outbreaks have been observed in neonatal 

intensive care units and in association with adult fecal 

incontinence. Other than the occasional transmission within 

health care settings, no worker-related HAV infections have 

been reported in the United States. Consistently, serologic 

studies in the United States have shown no or mildly 

increased risk of HAV infection in wastewater workers. 

Historically, HAV infection was highly endemic in institutions 

for persons with developmental disabilities. Now, persons 

with developmental disabilities typically live in group homes 

or residential facilities. Outbreaks can occur in these settings. 

Schools are not common sites for HAV transmission. Multiple 

cases among children at a school require investigation 

to identify a common source and efforts to improve 

immunization coverage. 
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9

Children generally have asymptomatic or unrecognized 

illnesses, so they may serve as a source of infection, particularly 

for household or other close contacts. 

In 2018, 5,026 (40%) of the 12,474 hepatitis A cases reported 

in the United States had a risk factor identified; the other 60% 

either had no risk factor identified or risk factor data were 

missing. Of the 40% with a risk factor identified, injection 

drug use was the most commonly identified risk factor. Other 

sources of infection identified in the United States in 2018 

included men who have sex with men, sexual/household 

contact with a hepatitis-A-infected person, other contact with 

a hepatitis A patient, and international travel. 

Secular Trends in the United States

Hepatitis A became nationally notifiable as a distinct entity in 

1966. During the prevaccine era in the United States, hepatitis 

A occurred in large, nationwide epidemics. The largest number 

of cases reported in one year (59,606) was in 1971. Prior to 

2000, the incidence of reported hepatitis A was substantially 

higher in the western United States than in other parts of the 

country. From 1987 to 1997, 11 mostly western states (Arizona, 

Alaska, Oregon, New Mexico, Utah, Washington, Oklahoma, 

South Dakota, Idaho, Nevada, California) accounted for 

50% of reported cases, but only 22% of the U.S. population. 

Historically, children age 2 through 18 years had the highest 

rates of hepatitis A (15 to 20 cases per 100,000 population in 

the early to mid-1990s).

In 1996, CDC’s Advisory Committee on Immunization Practices 

(ACIP) recommended administration of HepA vaccine to persons 

at increased risk for the disease, including international travelers, 

men who have sex with men, people who use non-injection 

and injection drugs, and children living in communities with 

high rates of disease. In 1999, ACIP also recommended routine 

vaccination for children living in 11 Western states with average 

hepatitis A rates of more than 20 cases per 100,000 population 

and recommended that vaccination be considered for children 

in an additional 6 states with rates of 10 to 20 cases per 100,000 

population. ACIP expanded these recommendations in 2006 

to include routine vaccination of children beginning at age 

12 months in all 50 states. In 2019, the ACIP recommended 

vaccination of all persons experiencing homelessness age 1 

year or older. In 2020, ACIP recommended vaccination of all 

children and adolescents age 2 through 18 years who have not 

previously received HepA vaccine and routine vaccination of all 

persons with HIV age 1 year or older.

Hepatitis A rates have been declining since vaccination 

initiation in 1996 and were less than 1 case per 100,000 until 

increases occurred due to widespread outbreaks among 

persons reporting drug use and homelessness. The number 

Hepatitis A Secular Trends 

in the United States

● Large, nationwide epidemic 

during prevaccine era

● Historically, children 2–18 had 

highest rates of hepatitis A (15 

to 20 cases per 100,000)

● Prior to 2000, incidence higher 

in Western states

● Rates declined 95.5% since 

vaccination initiation in 1996 

to 2011

● From 2016-2021, over 37,000 

outbreak-associated cases 

reported from 35 states
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of reported acute hepatitis A cases decreased 95.5% overall 

from 1996 to 2011. Many of the high-incidence states began 

routine hepatitis A vaccination programs for children in the 

late 1990s, and since 2002, rates have been similar in all parts 

of the country, ranging from 0.1 case per 100,000 population 

to 5.1 cases per 100,000 population. Since 2002, rates among 

children have declined. The wider use of vaccine is largely 

responsible for the marked decrease in hepatitis A rates in 

the United States, for the elimination of regional disparities in 

rates of infection, and for decreased infection rates in children. 

Beginning in the late 1990s, national age-specific rates 

declined more rapidly among children than adults; rates were 

similar among all age groups until the widespread person-toperson outbreaks occurred in 2017, primarily impacting adults 

and increasing rates among individuals age 20 years or older. 

Historic differences in rates among racial/ethnic populations 

have narrowed in the vaccine era. 

In 2018, 12,474 cases of acute hepatitis A were reported 

nationwide to CDC. The overall incidence rate for 2018 was 3.8 

cases per 100,000 population, an increase from recent years. The 

rate was similar for males and females but increased for persons 

older than age 20 years. In the United States, there have been 

decreases in incidence of hepatitis A due to universal childhood 

vaccination. However, this has resulted in the average age of 

hepatitis A-related hospitalizations and deaths increasing, and 

the proportion of persons hospitalized is more likely to have 

liver diseases and other comorbid medical conditions. Analysis 

of anti-HAV positivity prevalence, based on data from the 

National Health and Nutrition Examination Surveys (NHANES) 

conducted in 2007–2016, showed a significant increase among 

children age 6 through 19 years, and significant increases 

occurred in the proportion of children age 6 to 19 years with 

immune markers of protection, most likely from vaccination. 

Minimal change in anti-HAV positivity prevalence occurred 

among adults age 20 through 39 years, with 74% of adults 

being susceptible to disease. Significant decreases occurred in 

the proportion of adults age 40 years or older with protection. 

During 2007–2016, the prevalence of anti-HAV positivity among 

U.S.-born residents differed significantly by race/ethnicity. 

Overall, antibody positivity prevalence was lowest among 

non-Hispanic whites, intermediate among non-Hispanic blacks, 

and greatest among Hispanics across all age groups. 

During 2017, a total of 1,521 outbreak-associated HAV cases 

were reported from California, Kentucky, Michigan, and Utah, 

with 1,073 (71%) hospitalizations and 41 (3%) deaths; most 

infections were among persons reporting homelessness or 

injection or non-injection drug use. From August 2016 through 

January 2021, over 37,000 outbreak-associated cases had been 

reported from 35 states. 
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Among children born during 2016–2017, 85.8% had received 

at least 1 dose of HepA vaccine by age 24 months, an increase 

of 1.8 percentage points from 2014–2015. By age 35 months, 

76.9% had received at least 2 doses of HepA vaccine, a 2.0 

percentage point increase from 2014–2015. In 2019, 77.1%, 

of adolescents age 13-17 years had received at least 2 doses 

of HepA vaccine compared with 73.6% the year prior. For 

adults age 19 years or older, vaccination coverage in 2017 was 

reported at 10.9% for at least 2 doses.

Hepatitis A Vaccines

To produce HepA vaccines, cell culture–adapted virus is 

propagated in human fibroblasts, purified from cell lysates, 

inactivated with formalin, and adsorbed to an aluminum 

hydroxide adjuvant. Single-antigen HepA vaccine was licensed 

for use in the United States in 1995 (Havrix) and 1996 (Vaqta). In 

2001, a combination HepA-HepB vaccine (Twinrix) was licensed.

Characteristics

Single-antigen HepA vaccines (Havrix and Vaqta) are available 

in two formulations: pediatric and adult. The pediatric 

formulations of Havrix and Vaqta contain 720 ELISA units and 

25 HAV units per dose, respectively. The adult formulations of 

Havrix and Vaqta contain 1,440 ELISA units and 50 HAV units 

per dose, respectively. Twinrix contains 720 ELISA units of 

HepA vaccine and 20 micrograms of hepatitis B surface antigen 

protein per dose. HepA vaccines are administered by the 

intramuscular route. 

Twinrix contains yeast protein. Each dose of HepA vaccine 

contains aluminum as an adjuvant and neomycin as an 

antibiotic. HepA vaccines contain no preservative. Presentations 

of HepA vaccines contain latex rubber.

Vaccination Schedule and Use 

The pediatric formulations of Havrix and Vaqta vaccines are 

approved for persons age 12 months through 18 years. The 

adult formulations are approved for persons age 19 years or 

older. Both vaccines are approved as a 2-dose series. The 

second dose of Vaqta is administered 6 through 18 months 

after the first dose, and the second dose of Havrix is 

administered 6 through 12 months after the first dose. 

HepA-HepB (Twinrix) is licensed for persons age 18 years or 

older and administered as a 3-dose series at 0, 1, and 6 months. 

The first and second doses should be separated by at least 4 

weeks, and the second and third doses should be separated 

by at least 5 months. Twinrix is approved for persons age 18 

years or older and can be used in persons in this age group 

Hepatitis A Vaccines

● HepA (Havrix, Vaqta)

● HepA-HepB (Twinrix)

Hepatitis A Vaccine Characteristics

● Administered by intramuscular 

injection

● Contains aluminum adjuvant 

and neomycin

● Twinrix contains yeast protein

● Some presentations contain 

latex rubber

Hepatitis A Vaccination Schedule

● All children age 12 through 23 

months and all children and 

adolescents age 2 through 18 

years who have not previously 

received HepA vaccine

■ 2-dose series at 0, 6–18 

months (Vaqta)

■ 2-dose series at 0, 6–12 

months (Havrix)

● Adults age 19 years or older 

with risk factors

■ 2-dose series at 0, 6–18 

months (Vaqta)

■ 2-dose series at 0, 6–12 

months (Havrix)

■ 3-dose series at 0, 1, 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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with indications for both hepatitis A and hepatitis B vaccines. 

Twinrix is also approved using an alternative schedule with 

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

after the first dose.

All children should receive hepatitis A vaccine at age 1 year 

(i.e., 12 through 23 months). Vaccination should be completed 

according to the licensed schedules. All children and 

adolescents age 2 through 18 years who have not previously 

received HepA vaccine should be vaccinated (i.e., children and 

adolescents are recommended for catch-up vaccination). 

Adults age 19 years or older with risk factors should receive the 

adult formulation of HepA vaccine. Persons at increased risk for 

HAV infection, or who are at increased risk for severe disease 

from HAV infection, should be routinely vaccinated. 

Immune Globulin

Immune globulin (IG) provides protection against hepatitis A 

through passive transfer of antibody. GamaSTAN is a sterile, 

preservative-free solution of IG for intramuscular administration 

and is used for prophylaxis against diseases caused by HAV, 

measles, varicella, and rubella viruses. GamaSTAN is the only 

IG product approved by FDA for hepatitis A prophylaxis. In 

2017, the dosing of IG was changed to reflect decreased IgG 

anti-HAV potency, likely resulting from decreasing prevalence 

of previous HAV infection among plasma donors. GamaSTAN 

can be administered simultaneously with inactivated vaccines 

or toxoids in a different anatomic site (e.g., separate limbs) or 

at any time interval between doses. When MMR and varicella 

vaccines are recommended, they should be administered 

at least 2 weeks before or at least 6 months after the 

administration of IG.

Travelers

Persons at increased risk for hepatitis A should be identified and 

vaccinated. HepA vaccine is recommended for persons age 6 

months or older traveling to or working in countries where they 

would have a high or intermediate endemicity of HAV infection. 

These persons should be vaccinated, or receive IG if too young 

or contraindicated for vaccine, before departure. For travelers 

who are partially vaccinated already (i.e., did not receive a full 

vaccine series), a dose should be administered before travel, if 

needed, according to the vaccine schedule. If the first dose was 

given within the past 6 months, a second dose is not needed 

before travel.

HepA vaccine should be administered to infants age 6 through 

11 months traveling outside the United States when protection 

against HAV is recommended. The travel-related dose for infants 

age 6 through 11 months does not count toward the routine 

2-dose series. Therefore, the 2-dose HepA vaccination series 

should be initiated at age 12 months with the appropriate 

dosage and schedule. 
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9

Healthy persons age 12 months through 40 years who are 

planning on traveling to an area with high or intermediate 

hepatitis A endemicity and who have not received HepA 

vaccine should receive a single dose of HepA vaccine as soon 

as travel is considered and should complete the HepA vaccine 

series with the appropriate dosage and schedule.

Persons older than age 40 years, persons with 

immunocompromising conditions, and persons with chronic 

liver disease planning on traveling to an area with high or 

intermediate HAV endemicity should receive a single dose 

of HepA vaccine as soon as travel is considered. Persons 

traveling in less than 2 weeks should receive the initial dose 

of HepA vaccine and simultaneously may be administered IG 

in a different anatomic injection site (e.g., separate limbs). The 

HepA vaccine series should be completed according to the 

routine schedule.

Travelers for whom vaccine is contraindicated, who choose 

not to receive HepA vaccine when it is indicated, and 

persons younger than age 6 months old should receive 

IG. Persons traveling for up to 1 month should receive a 

single dose of IG (0.1 mL/kg). Persons traveling for up to 2 

months should receive IG at 0.2 mL/kg. Persons traveling for 

2 months or longer should receive IG at 0.2 mL/kg repeated 

every 2 months for the duration of travel. Infants age <6 

months traveling for 2 months or longer should receive IG at 

0.2 mL/kg repeated every 2 months for the duration of travel 

or until the infant is administered HepA vaccine (i.e., at age 

≥6 months). 

International Adoptees and Persons Who 

Anticipate Close Personal Contact with an 

International Adoptee

Screening asymptomatic people for hepatitis A is generally 

not recommended; however, clinicians may decide to test 

internationally adopted children for anti-HAV IgG and IgM 

to identify those who may be acutely infected and shedding 

virus and to make decisions regarding HepA vaccination.

HepA vaccination is recommended for all previously 

unvaccinated persons who anticipate close personal contact 

(e.g., household contact or regular babysitting) with an 

international adoptee from a country of high or intermediate 

endemicity during the first 60 days following arrival of the 

adoptee in the United States. The first dose of the 2-dose 

HepA vaccine series should be administered as soon as 

adoption is planned, ideally 2 or more weeks before the 

arrival of the adoptee.

Vaccination of Groups at 

Increased Risk

● Persons age 6 months or 

older traveling to or working 

in countries with high or 

intermediate endemicity 

of HAV infection

■ <6 months or contraindicated 

for vaccine: IG

■ 6–11 months: 1 dose of HepA 

vaccine (does not count 

toward routine 2-dose series)

■ 12 months–40 years and 

partially vaccinated or 

unvaccinated: 1 dose of HepA 

vaccine

■ >40 years, 

immunocompromised, or 

chronic liver disease: 1 dose 

of HepA vaccine when travel 

is considered; if traveling in 

less than 2 weeks, 1 dose of 

HepA vaccine and may be 

administered IG in a 

separate limb

● International adoptees and 

persons who anticipate close 

personal contact with an 

international adoptee

■ Adoptees: Consider testing 

for anti-HAV IgG and IgM to 

guide decision-making

■ Contacts: 2-dose series as 

soon as adoption is planned

● Persons experiencing 

homelessness, persons with 

chronic liver disease, persons 

with HIV: Routine vaccination
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Hepatitis A

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Persons Experiencing Homelessness

All persons age 1 year or older experiencing homelessness 

should be routinely vaccinated against hepatitis A. HepA 

vaccine should be integrated into routine preventive services 

for persons experiencing homelessness. A homeless person is 

defined as an individual: who lacks housing (without regard 

to whether the individual is a member of a family), including 

an individual whose primary residence during the night is a 

supervised public or private facility (e.g., shelter) that provides 

temporary living accommodations and an individual who 

is a resident in transitional housing; without permanent 

housing who may live on the streets; stay in a shelter, mission, 

single-room occupancy facility, abandoned building or vehicle; 

or in any other unstable or nonpermanent situation; who is 

“doubled up,” a term that refers to a situation where individuals 

are unable to maintain their housing situation and are forced to 

stay with a series of friends or extended family members.

Persons with Chronic Liver Disease 

Persons with chronic liver disease are at increased risk for 

fulminant hepatitis A should they become infected. Persons 

who have chronic liver disease, including those who either 

are awaiting or have received liver transplantation, should be 

vaccinated. Persons with chronic liver disease (including but 

not limited to persons with hepatitis B virus infection, hepatitis 

C virus infection, cirrhosis, fatty liver disease, alcoholic liver 

disease, autoimmune hepatitis, or an alanine aminotransferase 

(ALT) or aspartate aminotransferase (AST) level persistently 

greater than twice the upper limit of normal) should be 

routinely vaccinated against hepatitis A.

Persons with HIV

All persons with HIV infection age 1 year or older should be 

routinely vaccinated with HepA vaccine. Because the response 

to the vaccine might be reduced in persons with HIV infection 

who are immunosuppressed, postvaccination serologic testing 

should be performed for all persons with HIV infection at least 1 

month after completing the HepA vaccine series.

HepA vaccination is not routinely recommended for health care 

personnel, persons attending or working in child care centers, 

food service establishments and food handlers, or persons 

who work in liquid or solid waste management (e.g., sewer 

workers or plumbers). These persons have not been shown to 

be at increased risk for HAV infection. In addition, transmission 

of HAV from infected food handlers to susceptible consumers 

or restaurant patrons in the workplace is rare. As of 2020, 

persons who receive blood products for clotting disorders (e.g., 

hemophilia) are no longer specifically recommended to receive 

HepA vaccine.
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Vaccine Interchangeability

Limited data indicate that vaccines from different manufacturers 

are interchangeable. Completion of the series with the same 

product is preferable. However, if the originally used product is 

not available or not known, vaccination with either product is 

acceptable.

For both vaccines, the dosage of the second dose should be 

based on the person’s age at the time of the dose, not the age 

when the first dose was given. The minimum interval between 

the first and second doses of hepatitis A vaccine is 6 months. 

There is no maximum interval for either vaccine. A second dose 

given at 12 months or longer after the first dose need not be 

repeated.

Single-antigen hepatitis A and hepatitis B vaccines may be 

used in conjunction with Twinrix to form a complete series of 

these vaccines. Because the hepatitis B component of Twinrix 

is equivalent to a standard adult dose of hepatitis B vaccine, 

the schedule when vaccinating against hepatitis B is the same 

regardless of which hepatitis B vaccine (i.e., single-antigen 

or Twinrix) is used for which dose. Because the hepatitis A 

component of Twinrix is equivalent to a pediatric dose of 

hepatitis A vaccine, a series mixing the single-antigen hepatitis 

A vaccine and Twinrix is more complex. A person age 19 years 

or older who receives 1 dose of Twinrix may complete the 

hepatitis A series with 2 doses of adult formulation hepatitis A 

vaccine separated by at least 5 months. A person who receives 

2 doses of Twinrix may complete the hepatitis A series with 1 

dose of adult formulation hepatitis A vaccine 5 months after the 

second dose. A person who begins the hepatitis A series with 

single-antigen hepatitis A vaccine may complete the series with 

2 doses of Twinrix or 1 dose of adult formulation hepatitis A 

vaccine. Persons age 18 years should follow the same schedule 

using the pediatric formulation.
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Hepatitis A

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Vaccination series for adult using a combination of single-antigen HepA vaccine and Twinrix

1st Dose 2nd Dose* 3rd Dose†

TWINRIX TWINRIX TWINRIX

Single-Antigen

[Not Needed]§

Single-Antigen TWINRIX

Single-Antigen

[Not Needed]§

Single-Antigen TWINRIX TWINRIX

Single-Antigen

[Not Needed]§

Single-Antigen¶ [Not Needed]

Persons age 19 years and older—use adult formulation hepatitis A vaccine. Persons age 18 years old—use pediatric formulation 

hepatitis A vaccine.

*1 month after first dose (see § for exception)

†

5 months after second dose

§

A third dose is not needed if all three conditions are met: 1) person being vaccinated is not yet age 19 years old; 2) 6 months separate 

the first 2 doses; 3) protection against hepatitis B disease is NOT needed.

¶

6 months after first dose

Postexposure Prophylaxis (PEP)

HepA vaccine should be administered as soon as possible, 

within 2 weeks of exposure, to all unvaccinated persons age 12 

months or older who have recently been exposed to HAV. In 

addition to HepA vaccine, coadministration of IG (0.1 mL/kg) 

is recommended under certain circumstances and for persons 

age 40 years or older based on the provider’s risk assessment. 

Considerations regarding decision to use IG, vaccine, or both 

should include the ability of the person to develop a protective 

level of antibodies after receipt of HepA vaccine, the magnitude 

of the risk for HAV transmission from the exposure, and the 

availability of IG and vaccine.

Unvaccinated persons who are immunocompromised or have 

chronic liver disease and who have been exposed to HAV 

within the past 14 days should receive both IG (0.1 mL/kg) and 

HepA vaccine simultaneously in a different anatomic site (e.g., 

separate limbs) as soon as possible after exposure. 

When the dose of HepA vaccine administered for postexposure 

prophylaxis is the first dose the exposed person has received, a 

second dose should be administered 6 months after the first for 

long-term immunity; however, the second dose is not necessary 

for PEP.

IG (0.1 mL/kg) is recommended for postexposure prophylaxis for 

children younger than age 12 months and for persons for whom 

vaccine is contraindicated. 
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Immunogenicity and Vaccine Efficacy

Both monovalent HepA vaccines are highly immunogenic. More 

than 95% of adults will develop protective antibody within 

4 weeks of a single dose of either vaccine, and nearly 100% 

will seroconvert after receiving 2 doses. Among children and 

adolescents, more than 97% will be seropositive within a month 

of the first dose. In clinical trials, all recipients aged 2–18 years 

had protective levels of antibody after 2 doses.

Both vaccines are effective in preventing clinical hepatitis A. 

The efficacy of Havrix in protecting against clinical hepatitis A 

was 94% among 40,000 children in Thailand age 1 to 16 years 

who received 2 doses, 1 month apart, while living in villages 

with high HAV disease rates. The efficacy of Vaqta in protecting 

against clinical hepatitis A was 100% among 1,000 children in 

New York age 2 to 16 years who received 1 dose while living in a 

community with a high HAV disease rate.

The exact duration of protection after vaccination is unknown. 

Anti-HAV has been shown to persist for at least 25 years in 

adults administered inactivated vaccine as children with the 

3-dose schedule recommended prior to 1999, and anti-HAV 

persistence of at least 20 years also was demonstrated among 

persons vaccinated with a 2-dose schedule as adults. Detectable 

antibodies are estimated to persist for 40 years or longer based 

on mathematical modeling and anti-HAV kinetic studies.

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. 

Contraindications to Twinrix include the contraindications to 

HepB vaccine. 

Vaccine Safety

The most frequently reported adverse events to the Vaccine 

Adverse Event Reporting System (VAERS) for single-antigen 

hepatitis A vaccines were fever, injection site erythema, injection 

site swelling, and rash. The most frequently reported adverse 

events for combination hepatitis A vaccine and hepatitis B 

vaccine were fever, headache, injection site pain, and dizziness.

Hepatitis A Vaccine Efficacy

● Highly immunogenic

● More than 95% of adults 

develop protective antibody 

within 4 weeks of a single dose

● More than 97% of children and 

adolescents will be seropositive 

within 1 month of the first dose

Hepatitis A Vaccine 

Contraindications and Precautions

● Contraindication

■ Severe allergic reaction 

to vaccine component or 

following a prior dose

● Precaution

■ Moderate or severe 

acute illness

Hepatitis A Vaccine Safety

● Single-antigen HepA vaccines: 

Fever, injection site erythema, 

injection site swelling, rash

● HepA-HepB vaccine: Fever, 

headache, injection site 

pain, dizziness
138

Hepatitis A

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Vaccination in Pregnancy

A review of VAERS did not identify any concerning patterns 

of adverse events in pregnant women or their infants after 

vaccination with Havrix, Vaqta, or Twinrix during pregnancy. 

A multisite study in CDC’s Vaccine Safety Datalink (VSD) 

of maternal HepA vaccination found that HepA vaccine 

administration during pregnancy was not associated with 

increased risk for a range of adverse events examined among 

pregnancies resulting in live births. However, an association 

was found between maternal HepA vaccination and infants 

who were small for gestational age. Investigators believe this 

association was likely due to unmeasured confounding but 

might warrant additional consideration.

Vaccine Storage and Handling

HepA vaccines 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 for Hepatitis A

The 2019 Council of State and Territorial Epidemiologists 

surveillance case definition for hepatitis A clinical criteria 

includes an acute illness with a discrete onset of any sign 

or symptom consistent with acute viral hepatitis (e.g., fever, 

headache, malaise, anorexia, nausea, vomiting, diarrhea, and 

abdominal pain), and either a) jaundice or elevated bilirubin 

levels greater than or equal to 3 mg/dL, or b) elevated serum 

ALT levels greater than 200 IU/L and the absence of a more 

likely diagnosis. Since hepatitis A cannot be differentiated 

from other types of viral hepatitis on clinical or epidemiologic 

features alone, serologic evidence of HAV infection or detection 

of HAV through nucleic acid testing is necessary. The laboratory 

criteria for hepatitis A requires the presence of HAV-specific 

IgM antibody or a positive nucleic acid amplification test. For 

additional information on the case definition and guidance on 

case and contact investigations, please consult the Manual for 

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

vaccines/pubs/surv-manual/index.html. 
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Acknowledgements

The editors would like to acknowledge Clive Brown, Maria Cano, 

and Jennifer Hamborsky for their contributions to this chapter.

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