Hepatitis A Questions and Answers for Health Professionals

Index of Questions

Overview and Statistics

What is the case definition for acute Hepatitis A?

The clinical case definition for acute viral hepatitis is 1) discrete onset of symptoms (e.g., nausea, anorexia, fever, malaise, or abdominal pain) and 2) jaundice or elevated serum aminotransferase levels. Because the clinical characteristics are the same for all types of acute viral hepatitis, Hepatitis A diagnosis must be confirmed by a positive serologic test for immunoglobulin M (IgM) antibody to Hepatitis A virus, or the case must meet the clinical case definition and occur in a person who has an epidemiologic link with a person who has laboratory-confirmed Hepatitis A (i.e., household or sexual contact with an infected person during the 15–50 days before the onset of symptoms).

The case definition for acute Hepatitis A is available at the following link:

Acute Hepatitis A

Additional guidance on viral hepatitis surveillance and case management is available at http://www.cdc.gov/hepatitis/SurveillanceGuidelines.htm.

How common is Hepatitis A virus (HAV) infection in the United States?

Hepatitis A rates in the United States have declined by 95% since Hepatitis A vaccine first became available in 1995.

In 2013, 1,781 acute symptomatic cases of hepatitis A were reported. These 1,781 hepatitis A cases represent an increase of 14% from 1,562 cases in 2012, due to an outbreak from imported pomegranate arils consumed by persons in several southwestern states and Hawaii in 2013. After adjusting for asymptomatic infection and underreporting, the estimated number of new infections was 3,473.

How is HAV transmitted?

• Person-to-person transmission through the fecal-oral route (i.e., ingestion of something that has been contaminated with the feces of an infected person) is the primary means of HAV transmission in the United States. Most infections result from close personal contact with an infected household member or sex partner.
• Common-source outbreaks and sporadic cases also can occur from exposure to fecally contaminated food or water. Uncooked HAV-contaminated foods have been recognized as a source of outbreaks. Cooked foods also can transmit HAV if the temperature during food preparation is inadequate to kill the virus or if food is contaminated after cooking, as occurs in outbreaks associated with infected food handlers. Waterborne outbreaks are infrequent in developed countries with well-maintained sanitation and water supplies.

Who is at increased risk for acquiring HAV infection?

• Travelers to countries with high or intermediate endemicity of HAV infection
• Men who have sex with men
• Users of injection and non-injection illegal drugs
• Persons with clotting factor disorders
• Persons working with nonhuman primates

What are the signs and symptoms of HAV infection?

• Fever
• Fatigue
• Loss of appetite
• Nausea
• Vomiting
• Abdominal pain
• Dark urine
• Clay-colored bowel movements
• Joint pain
• Jaundice

In children aged <6 years, 70% of infections are asymptomatic; if illness does occur, it is typically not accompanied by jaundice. Among older children and adults, infection is typically symptomatic, with jaundice occurring in >70% of patients.

When symptoms occur, how long do they usually last?

Symptoms usually last less than 2 months, although 10%–15% of symptomatic persons have prolonged or relapsing disease for up to 6 months.

What is the incubation period for Hepatitis A?

The average incubation period for Hepatitis A is 28 days (range: 15–50 days).

How long does HAV survive outside the body? How can the virus be killed?

HAV can live outside the body for months, depending on the environmental conditions. The virus is killed by heating to >185 degrees F (>85 degrees C) for one minute. However, the virus can still be spread from cooked food if it is contaminated after cooking. Adequate chlorination of water, as recommended in the United States, kills HAV that enters the water supply.

Can Hepatitis A become chronic?

No. Hepatitis A does not become chronic.

Can persons become reinfected with HAV after recovering from Hepatitis A?

No. IgG antibodies to HAV, which appear early in the course of infection, provide lifelong protection against the disease.

How is HAV infection prevented?

Vaccination with the full, two-dose series of Hepatitis A vaccine is the best way to prevent HAV infection. Hepatitis A vaccine has been licensed in the United States for use in persons 12 months of age and older. The vaccine is recommended for persons who are more likely to get HAV infection or are more likely to get seriously ill if they get Hepatitis A, and for any person wishing to obtain immunity (see Who should be vaccinated against Hepatitis A?).

Immune globulin is available for short-term protection (approximately 3 months) against Hepatitis A, both pre- and post-exposure. Immune globulin must be administered within 2 weeks after exposure for maximum protection.

Good hygiene — including handwashing after using the bathroom, changing diapers, and before preparing or eating food — is also integral to Hepatitis A prevention, given that the virus is transmitted through the fecal–oral route. Environmental surfaces can be cleaned with a freshly prepared solution of 1:100 dilution of household bleach.

Hepatitis A Vaccination

Who should be vaccinated against Hepatitis A?

Hepatitis A vaccination is recommended for all children at age 1 year, for persons who are at increased risk for infection, for persons who are at increased risk for complications from Hepatitis A, and for any person wishing to obtain immunity. The following groups are recommended to receive Hepatitis A vaccination:

Which Hepatitis A vaccines are licensed for use in the United States?

Two single-antigen Hepatitis A vaccines, HAVRIX® (manufactured by GlaxoSmithKline) and VAQTA® (manufactured by Merck & Co., Inc), are currently licensed in the United States. A combination vaccine, TWINRIX® (manufactured by GlaxoSmithKline), contains both HAV (in a lower dosage; see table) and Hepatitis B virus antigens. All are inactivated vaccines.

What are the dosages and schedules for Hepatitis A vaccines?

Licensed dosages and schedules for HAVRIX ® 1
Age	Dose (ELISA units)2	Volume (mL)	No. of doses	Schedule (mos)3
12 mos–18 yrs	720	0.5	2	0,6-12
≥19 years	1,440	1.0	2	0,6-12

¹Hepatitis A vaccine, inactivated, GlaxoSmithKline.
²Enzyme-linked immunosorbent assay units.
³0 months represents timing of the initial dose; subsequent numbers represent months after the initial dose.

Licensed dosages and schedules for VAQTA ® 1
Age	Dose (U.)2	Volume (mL)	No. of doses	Schedule (mos)3
12 mos–18 yrs	25	0.5	2	0,6-18
≥19 years	50	1.0	2	0,6-18

¹Hepatitis A vaccine, inactivated, Merck & Co., Inc.
²Units.
³0 months represents timing of the initial dose; subsequent numbers represent months after the initial dose.

TWINRIX ^{® 1} (HepAHepB) Vaccine Schedule (Not recommended for post exposure prophylaxis)

Licensed dosages and schedules for TWINRIX ® 1
Age	Dose (ELISA units)2	Volume (mL)	No. of doses	Schedule
≥ 18 yrs	720	1.0	3	0, 1, 6 mos
≥ 18 yrs	720	1.0	4	0, 7, 21–30 days + 12 mos3

¹Combined Hepatitis A and Hepatitis B vaccine, inactivated, GlaxoSmithKline.
²Enzyme-linked immunosorbent assay units.
³This 4-dose schedule enables patients to receive 3 doses in 21 days; this schedule is used prior to planned exposure with short notice and requires a fourth dose at 12 months.

How long does protection from Hepatitis A vaccine last?

A recent review by an expert panel, which evaluated the projected duration of immunity from vaccination, concluded that protective levels of antibody to HAV could be present for at least 25 years in adults and at least 14–20 years in children.

Can Hepatitis A vaccine be administered concurrently with other vaccines?

Yes. Hepatitis B, diphtheria, poliovirus (oral and inactivated), tetanus, oral and intramuscular typhoid, cholera, Japanese encephalitis, rabies, and yellow fever vaccines and immune globulin can be given at the same time that Hepatitis A vaccine is given, but at a different injection site.

Can a patient receive the first dose of Hepatitis A vaccine from one manufacturer and the second (last) dose from another manufacturer?

Yes. Although studies have not been done to examine this issue, there is no reason to believe that using single-antigen vaccine from different manufacturers would be a problem.

What should be done if the second (last) dose of Hepatitis A vaccine is delayed?

The second dose should be administered as soon as possible. The first dose does not need to be readministered.

Can Hepatitis A vaccine be given during pregnancy?

The safety of Hepatitis A vaccination during pregnancy has not been determined; however, because the vaccine is produced from inactivated HAV, the theoretical risk to the developing fetus is expected to be low. The risk associated with vaccination, however, should be weighed against the risk for Hepatitis A in women who might be at high risk for exposure to HAV.

Can Hepatitis A vaccine be given to immunocompromised persons (e.g., persons on hemodialysis or persons with AIDS)?

Yes. Because Hepatitis A vaccine is inactivated, no special precautions need to be taken when vaccinating immunocompromised persons.

Is it harmful to administer an extra dose(s) of Hepatitis A or Hepatitis B vaccine or to repeat the entire vaccine series if documentation of vaccination history is unavailable?

No. If necessary, administering extra doses of Hepatitis A or Hepatitis B vaccine is not harmful.

Should prevaccination testing be performed before administering Hepatitis A vaccine?

• Persons who were born in geographic areas with high or intermediate prevalence of HAV infection
• Older adolescents and adults in certain population groups (i.e., American Indians, Alaska Natives, and Hispanics)
• Adults in groups that have a high prevalence of infection (e.g., injection drug users)

Prevaccination testing might also be warranted for all older adults. The decision to test should be based on 1) the expected prevalence of immunity, 2) the cost of vaccination compared with the cost of serologic testing, and 3) the likelihood that testing will not interfere with initiation of vaccination.

Should postvaccination testing be performed?

No. Postvaccination testing is not indicated because of the high rate of vaccine response among adults and children. In addition, not all testing methods approved for routine diagnostic use in the United States have the sensitivity to detect low, but protective, anti-HAV concentrations after vaccination.

Which groups do NOT need routine vaccination against Hepatitis A?

Hepatitis A and International Travel

Who should receive protection against Hepatitis A before travel?

All susceptible persons traveling to or working in countries that have high or intermediate rates of Hepatitis A should be vaccinated or receive immune globulin (IG) before traveling. Persons from developed countries who travel to developing countries are at high risk for Hepatitis A. The risk for Hepatitis A exists even for travelers to urban areas, those who stay in luxury hotels, and those who report that they have good hygiene and that they are careful about what they drink and eat. For more information on international travel and HAV, see CDC's travel page at http://wwwn.cdc.gov/travel/yellowBookCh4-HepA.aspx .

How soon before travel should the first dose of Hepatitis A vaccine be given?

The first dose of Hepatitis A vaccine should be administered as soon as travel is considered.

Previously, Hepatitis A vaccination was recommended to be administered at least 2–4 weeks before departure to an area with intermediate or high rates of Hepatitis A. Travelers who were departing in less than 2 weeks were recommended to receive receive immune globulin (IG) for short-term protection.

However, on the basis of data indicating that immune globulin and vaccine have equivalent postexposure efficacy among healthy persons aged ≤40 years, the Advisory Committee on Immunization Practices (ACIP) has amended its guidelines for Hepatitis A vaccination for travelers. ACIP now recommends that one dose of single-antigen Hepatitis A vaccine administered at any time before departure may provide adequate protection for most healthy persons.

For optimal protection, older adults, immunocompromised persons, and persons with chronic liver disease or other chronic medical conditions who are planning to depart in ≤2 weeks should receive the initial dose of vaccine and also can simultaneously be administered IG (0.02 mL/kg) at a separate anatomic injection site.

What should be done if a traveler cannot receive Hepatitis A vaccine?

Travelers who are allergic to a vaccine component, who elect not to receive vaccine, or who are aged <12 months should receive a single dose of IG (0.02 mL/kg), which provides effective protection against Hepatitis A virus infection for up to 3 months. Travelers whose travel period exceeds 2 months should be administered IG at 0.06 mL/kg; administration must be repeated if the travel period exceeds 5 months.

What should be done for travelers less than 12 months of age?

Immune globulin is recommended because Hepatitis A vaccine is currently not approved for use in this age group.

Postexposure Prophylaxis for Hepatitis A

What are the current CDC guidelines for postexposure protection against Hepatitis A?

Until recently, an injection of immune globulin (IG) was the only recommended way to protect people after they have been exposed to Hepatitis A virus. In June 2007, U.S. guidelines were revised to allow for Hepatitis A vaccine to be used after exposure to prevent infection in healthy persons aged 1–40 years.

• For healthy persons aged 12 months–40 years, single-antigen Hepatitis A vaccine at the age-appropriate dose is preferred to IG because of the vaccine’s advantages, including long-term protection and ease of administration, as well as the equivalent efficacy of vaccine to IG.
• For persons aged 40 years and older, IG is preferred because of the absence of information regarding vaccine performance in this age group and because of the more severe manifestations of Hepatitis A in older adults. The magnitude of the risk of HAV transmission from the exposure should be considered in decisions to use vaccine or IG in this age group.
• Vaccine can be used if IG cannot be obtained.
• IG should be used for children aged less than12 months, immunocompromised persons, persons with chronic liver disease, and persons who are allergic to the vaccine or a vaccine component (see Footnote).

Footnote:

• CDC does not have official guidance to define all subgroups of persons recommended to receive IG.
• IG is indicated for persons at increased risk of severe or fatal hepatitis A infection. These persons include adults older than 40 years of age, particularly adults 75 years and older, persons with chronic liver disease (e.g., cirrhosis), and those who are immunocompromised.
• IG is indicated for persons with decreased response to hepatitis A vaccine. Based on available data such persons include those with HIV/AIDs, persons undergoing hemodialysis, recipients of solid organ, bone marrow or stem cell transplants, persons with chronic liver disease (e.g., cirrhosis), and other patients unlikely to develop an adequate immune response. Also, antibody response after a single dose of hepatitis A vaccine in persons older than 40 years may be reduced, but data are limited.
• Immunocompromised persons generally are incapable of developing a normal immune response, usually as a result of disease, malnutrition, or immunosuppressive therapy. IG is indicated for patients who might include those receiving high dose steroids, chemotherapy, immunomodulators, and those who have primary immunodeficiency conditions. Clinical guidance should be obtained if the immune status is unclear.

Who requires protection (i.e., immune globulin (IG) or Hepatitis A vaccine) after exposure to HAV?

• Household and sex contacts
• Persons who have shared illicit drugs with someone with Hepatitis A

Consideration should also be given to providing IG or Hepatitis A vaccine to persons with other types of ongoing, close personal contact with a person with Hepatitis A (e.g., a regular babysitter or caretaker).

• Postexposure prophylaxis (PEP) should be administered to all previously unvaccinated staff and attendees of child care centers or homes if 1) one or more cases of Hepatitis A are recognized in children or employees or 2) cases are recognized in two or more households of center attendees.
• In centers that provide care only to older children who no longer wear diapers, PEP need be administered only to classroom contacts of the index patient (i.e., not to children or staff in other classrooms).
• When an outbreak occurs (i.e., Hepatitis A cases in three or more families), PEP should also be considered for members of households that have diaper-wearing children attending the center.

Persons exposed to a common source, such as an infected food handler. If a food handler receives a diagnosis of Hepatitis A, post-exposure prophylaxis (PEP) should be administered to other food handlers at the same establishment. Because transmission to patrons is unlikely, PEP administration to patrons typically is not indicated but may be considered if 1) during the time when the food handler was likely to be infectious, the food handler both directly handled uncooked foods or foods after cooking and had diarrhea or poor hygienic practices, and 2) patrons can be identified and treated within 2 weeks of exposure.

In settings in which repeated exposures to HAV might have occurred, such as institutional cafeterias, stronger consideration of PEP use might be warranted.

If a case of Hepatitis A is found in a school, hospital, or office setting, what should be done?

If a single case of Hepatitis A is identified in a school (other than a child care setting in which children wear diapers), office, or other work setting, and if the source of infection is outside the school or work setting, PEP (i.e., injection of IG or Hepatitis A vaccine) is not routinely recommended. Similarly, when a person who has Hepatitis A is admitted to a hospital, staff should not routinely be administered PEP; instead, careful hygienic practices should be emphasized.

However, if it is determined that Hepatitis A has been spread among students in a school or among patients and staff in a hospital, PEP should be administered to unvaccinated persons who have had close contact with an infected person.