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Posted on November 02, 2007

 

Hepatitis A, caused by infection with HAV, has an incubation period of approximately 28 days (range: 15–50 days). HAV replicates in the liver and is shed in high concentrations in feces from 2 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, 10%–15% of patients might 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 >80% 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.

 

HAV infection is primarily transmitted by the fecal-oral route, by either person-to-person contact, or through consumption of contaminated food or water. Although viremia occurs early in infection and can persist for several weeks after onset of symptoms, bloodborne transmission of HAV is uncommon. HAV occasionally might be detected in saliva in experimentally infected animals, but transmission by saliva has not been demonstrated.

 

In the United States, nearly half of all reported hepatitis A cases have no specific risk factor identified. Among adults with identified risk factors, the majority of cases are among MSM, persons who use illegal drugs, and international travelers. Because transmission of HAV during sexual activity probably occurs because of fecal-oral contact, measures typically used to prevent the transmission of other STDs (e.g., use of condoms) do not prevent HAV transmission. In addition, efforts to promote good personal hygiene have not been successful in interrupting outbreaks of hepatitis A. Vaccination is the most effective means of preventing HAV transmission among persons at risk for infection, many of whom might seek services in STD clinics.

 

Diagnosis

 

The diagnosis of hepatitis A cannot be made on clinical grounds alone and requires serologic testing. The 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 might be positive after hepatitis A vaccination.

 

Treatment

 

Patients with acute hepatitis A 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 critical 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 hepatitis A.

 

Prevention

 

Two products are available for the prevention of HAV infection: hepatitis A vaccine (Table 2) and immune globulin (Ig) for IM administration. Hepatitis A vaccines are prepared from formalin-inactivated, cell-culture–derived HAV and have been available in the United States since 1995, initially for persons aged ≥2 years. In 2005, the vaccines were approved by FDA for persons aged ≥12 months. Administered IM in a 2-dose series, these vaccines induce protective antibody levels in virtually all adults. By 1 month after the first dose, 94%–100% of adults have protective antibody levels; 100% of adults develop protective antibody after a second dose. In randomized controlled trials, the equivalent of 1 dose of hepatitis A vaccine administered before exposure has been 94%–100% effective in preventing clinical hepatitis A. Kinetic models of antibody decline indicate that protective levels of antibody persist for at least 20 years.

 

TABLE 2. Recommended regimens: dose and schedule for hepatitis A vaccines


VaccineAge(years)Dose*Volume(mL)Two-does schedule(mos)†
HAVRIX§1-18720 (EL.U.)0.50, 6–12
>181,440 (EL.U.)1.00, 6–12
VAQTA¶1-1825 (U)0.50, 6–18
>1850 (U)1.00, 6–18

* EL.U. = enzyme-linked immunosorbent assay (ELISA) units. U = units.
† 0 months represents the timing of the initial dose; subsequent numbers represent the months after the initial dose.
§ Hepatitis A vaccine, inactivated, GlaxoSmithKline Biologicals. This vaccine also is licensed for a 3-dose series in children aged 1–18 years, with 360 EL.U., 0.5-mL doses at 0, 1, and 6–12 months.
¶ Hepatitis A vaccine, inactivated, Merck & Co., Inc.

A combined hepatitis A and hepatitis B vaccine have been developed and licensed for use as a 3-dose series in adults aged ≥18 years. When administered IM on a 0-, 1-, and 6-month schedule, the vaccine has equivalent immunogenicity to that of the monovalent vaccines.

 

  • Hepatitis A vaccine is available for eligible children and adolescents aged <19 years through the Vaccines for Children program (telephone: 800-232-2522).
  • 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 hepatitis B surface antigen, antibodies to HIV and HCV, and HCV RNA. In addition, the process used to manufacture Ig inactivates viruses (e.g., HBV, HCV, and HIV). When administered IM before or within 2 weeks after exposure to HAV, Ig is >85% effective in preventing HAV infections.

 

Preexposure Immunization

 

Persons in the following groups who are likely to be treated in STD clinic settings should be offered hepatitis A vaccine: 1) all MSM; 2) illegal drug users (both injecting and noninjecting drugs); and 3) persons with CLD, including persons with chronic HBV and HCV infection who have evidence of CLD.

 

Prevaccination Serologic Testing for Susceptibility

 

Approximately one third of the U.S. population has serologic evidence of previous HAV infection, which increases directly with age and reaches 75% among persons aged >70 years. Screening for HAV infection might be cost-effective in populations where the prevalence of infection is likely to be high (e.g., persons aged >40 years and persons born in areas of high HAV endemicity). The potential cost-savings of testing should be weighed against the cost and the likelihood that testing will interfere with initiating vaccination. Vaccination of a person who is already immune is not harmful.

 

TABLE 3. Recommended doses of currently licensed formulations of adolescent and adult hepatitis B vaccines


GroupSingle-antigen vaccineCombination vaccine
Recombivax HB®Engerix-B®Twinrix®*
Dose
(µg)
Volume
(mL)
Dose
(µg)
Volume
(mL)
Dose
(µg)
Volume
(mL)
Adolescents aged 11–19 yrs§50.5100.5NANA
Adolescents aged 11–15 yrs**101.0NANANANA
Adults aged ≥20 yrs101.0201.0201.0
Hemodialysis patients and other immunocompromised persons aged <20 yrs§50.5100.5NANA
Hemodialysis patients and other immunocompromised persons aged ≥20 yrs401.040§§2.0NANA

* Combined hepatitis A and hepatitis B vaccine. This vaccine is recommended for persons aged >18 years who are at increased risk for both hepatitis B and hepatitis A virus infections.
† Recombinant hepatitis B surface antigen protein dose in micrograms.
§ Pediatric formulation administered on a 3-dose schedule; higher doses might be more immunogenic, but no specific recommendations have been made.
¶ Not applicable.
** Adult formulation administered on a 2-dose schedule.
Dialysis formulation administered on a 3-dose schedule at 0, 1, and 6 months.
§§ Two 1.0-mL doses of the adult formulation administered at one site on a 4-dose schedule at 0, 1, 2, and 6 months.

Postvaccination Serologic Testing

 

Postvaccination serologic testing is not indicated because the majority of persons respond to the vaccine. In addition, the commercially available serologic test is not sensitive enough to detect the low, but protective, levels of antibody produced by vaccination.

 

Postexposure Prophylaxis

 

Previously unvaccinated persons exposed to HAV (e.g., through household or sexual contact or by sharing illegal drugs with a person who has hepatitis A) should be administered a single IM dose of Ig (0.02 mL/kg) as soon as possible but not >2 weeks after exposure. Persons who have had 1 dose of hepatitis A vaccine at least 1 month before exposure to HAV do not need Ig. If hepatitis A vaccine is recommended for a person receiving Ig, it can be administered simultaneously at a separate anatomic injection site. The use of hepatitis A vaccine alone is not recommended for PEP.

 

Special Considerations

 

Limited data indicate that vaccination of persons with CLD and of HIV-infected persons results in lower seroprotection rates and antibody concentrations. In HIV-infected persons, antibody response might be directly related to CD4+ levels.


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