Hepatitis A Virus (HAV) Infection

HAV infection has an incubation period of approximately 28 days (range: 15–50 days) (1296). HAV replicates in the liver and is shed in high concentrations in feces from 2–3 weeks before to 1 week after the onset of clinical illness. HAV infection produces a self-limited disease that does not result in chronic infection or chronic liver disease. However, approximately 10% of patients experience a relapse of symptoms during the 6 months after acute illness. Acute liver failure from hepatitis A is rare (overall case-fatality rate: 0.5%). The risk for symptomatic infection is directly related to age, with approximately 70% of adults having symptoms compatible with acute viral hepatitis and the majority of children having either asymptomatic or unrecognized infection. Antibody produced in response to HAV infection persists for life and confers protection against reinfection (1297).

HAV infection is primarily transmitted by the fecal-oral route, by either person-to-person contact or through consumption of contaminated food or water (1298). Transmission of HAV during sexual activity probably results from fecal-oral contact. Although viremia occurs early during infection and can persist for weeks after symptom onset, bloodborne transmission of HAV is uncommon (1299). Transmission by saliva has not been demonstrated.

In the United States, of the hepatitis A cases accompanied by risk information, a particular risk was identified among only 23.8% (13,372). Among cases with a risk factor identified, a recognized foodborne or waterborne outbreak was the most commonly identified risk (49.6%). Other infection sources identified in the United States include MSM; persons who use injecting drugs; sexual and household contacts; those experiencing homelessness; international travelers; those with children attending a nursery, childcare, or preschool; and persons working in such settings (13,372).

Diagnostic Considerations

Diagnosis of HAV infection cannot be made on a clinical basis alone but requires serologic testing. Presence of IgM antibody to HAV is diagnostic of acute HAV infection. A positive test for total anti-HAV indicates immunity to HAV infection but does not differentiate current from previous HAV infection. Although usually not sensitive enough to detect the low level of protective antibody after vaccination, anti-HAV tests also might be positive after hepatitis A vaccination.

Treatment

Patients with acute HAV infection usually require only supportive care, with no restrictions in diet or activity. Hospitalization might be necessary for patients who become dehydrated because of nausea and vomiting and is crucial for patients with signs or symptoms of acute liver failure. Medications that might cause liver damage or are metabolized by the liver should be used with caution among persons with HAV infection.

Prevention

Vaccination is the most effective means of preventing HAV transmission among persons at risk for infection (e.g., MSM, injecting drug users, and persons with chronic liver disease) who did not receive hepatitis A vaccination during childhood. Hepatitis A vaccines are prepared from formalin-inactivated, cell-culture–derived HAV. Two monovalent vaccines (Havrix and Vaqta are approved by FDA for persons aged ≥12 months (Table 3). These vaccines are available for eligible children and adolescents aged <19 years through the VFC program (https://www.cdc.gov/vaccines/programs/vfc/index.html). Administered IM in a 2-dose series at 0 and 6–12 months, hepatitis A vaccines induce protective antibody levels among virtually all adults. By 1 month after the first dose, 94%–100% of adults have protective antibody levels, and after a second dose, 100% achieve protective levels (1297,1300,1301). Kinetic models of antibody decrease among adults indicate that protective levels persist for >40 years (1302–1304). A study of Alaska Natives demonstrated that seropositivity for hepatitis A persists for >20 years after completing 2-dose vaccination at age 12–21 months (1302). Anti-HAV persistence of >20 years was demonstrated among immunocompetent adults vaccinated with a 2-dose hepatitis A schedule as adults (1303,1305). A combined hepatitis A and hepatitis B vaccine (Twinrix) has been developed and licensed for use as a 3-dose series for adults aged ≥18 years at risk for HAV or HBV infections. When administered IM on a 0-, 1-, and 6-month schedule, the vaccine has equivalent immunogenicity to that of the monovalent hepatitis A vaccines.

Pre-Exposure Vaccination

Persons at risk for HAV infection (Box 5) (1297) should be offered vaccine (Table 3). If persons are at risk for both HAV and HBV, the combined vaccine can be considered.

Prevaccination Serologic Testing

Among U.S.-born adults aged >20 years, HAV susceptibility prevalence (i.e., total antibody to HAV was negative) was 74.1% (95% CI: 72.9%–75.3%) during 2007–2016 (1306). Prevaccination serologic testing for HAV immunity before vaccination is not routinely recommended; however, it can be considered in specific settings to reduce costs by not vaccinating persons who are already immune. Prevaccination serologic testing should not be a barrier to vaccination of susceptible persons, especially for populations that are difficult to access. If prevaccination testing is performed, commercially available tests for total anti-HAV or IgG anti-HAV should be used (1297).

Persons for whom prevaccination testing will likely be most cost-effective include adults who were either born in or lived for extensive periods in geographic areas where HAV endemicity is high or intermediate (1297). Prevaccination serologic testing of children is not indicated because of the low prevalence of infection among that age group.

For populations who are expected to have high rates of previous HAV infection, vaccination history should be obtained when feasible before testing or vaccination. Vaccination should not be postponed if vaccination history cannot be obtained, records are unavailable, or prevaccination testing is infeasible. Vaccinating persons immune from natural infection carries no known risk, nor does giving extra doses of hepatitis A vaccine (1307). Vaccination of a person who is already immune is not harmful. Persons who have a documented history of ≥2 doses of hepatitis A vaccine do not need further vaccination or serologic testing.

Postvaccination Serologic Testing

Serologic testing for immunity is unnecessary after routine vaccination of infants, children, or adults (1297). Testing for anti-HAV antibody after vaccination is recommended for persons whose subsequent clinical management depends on knowledge of their immune status and persons for whom revaccination might be indicated (e.g., persons with HIV infection and other immunocompromising conditions).

Postexposure Prophylaxis

Persons who recently have been exposed to HAV and who previously have not received hepatitis A vaccine should be administered a single dose of monovalent hepatitis A vaccine or immunoglobulin (IG) (0.1 mL/kg body weight) as soon as possible, ideally <2 weeks after exposure because the efficacy of vaccine or IG when administered >2 weeks after exposure has not been established (1297). In most cases, monovalent hepatitis A vaccine at the age-appropriate dose is preferred over IG for PEP. Advantages of hepatitis A vaccine for PEP include induction of active immunity, longer-term protection, ease of administration, and better acceptability and availability. Decisions to use vaccine versus IG should be guided by patient characteristics associated with more severe manifestations of HAV infection (e.g., older age, immunocompromising conditions, and chronic liver disease) and the magnitude of the risk for HAV transmission resulting from the exposure (1297).

IG should be used for children aged <6 months, immunocompromised persons, persons with chronic liver disease, and persons for whom vaccine is contraindicated. IG can be administered to persons aged >40 years, in addition to hepatitis A vaccine (1297).

IG administered IM can provide PEP against HAV (Table 4). IG is a sterile solution of concentrated immunoglobulins prepared from pooled human plasma processed by cold ethanol fractionation. In the United States, IG is produced only from plasma that has tested negative for HBsAg, antibodies to HIV and HCV, and HIV and HCV RNA. In addition, the process used to manufacture IG inactivates viruses (e.g., HBV, HCV, and HIV). When administered IM <2 weeks after exposure to HAV, IG is >85% effective in preventing HAV infection (1308).

If IG is administered to persons for whom hepatitis A vaccine also is recommended, a dose of vaccine should be provided simultaneously with IG in different anatomic sites (e.g., different limbs) as soon as possible, and the second vaccine dose should be administered according to the licensed schedule to complete the series. The combined vaccine can be considered for persons among whom both hepatitis A and hepatitis B vaccine is recommended (13,1297,1302–1304).

Special Considerations

For persons with HIV infection, antibody response can be directly related to CD4⁺ T-cell levels. Although persons with HIV who have lower CD4⁺ T-cell counts or percentages might have a weaker response to the vaccine, vaccination should not be delayed for the CD4⁺ T-cell count to exceed a certain threshold because of the prolonged risk for HAV exposure created by missed opportunities to vaccinate.

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