Discussion

General Approach Following Exposure to Hepatitis A Virus

Hepatitis A virus (HAV) is primarily transmitted via the fecal-oral route, through either person-to-person contact or by ingestion of contaminated food or water[1]. The evaluation and management of a patient potentially exposed to HAV entails a three-part strategy. First, the context in which the exposure occurred should be considered, and the necessity of postexposure prophylaxis assessed. Second, if this assessment reveals that the exposure warrants postexposure prophylaxis, immune globulin (IG) or single-antigen hepatitis A vaccine should be administered, depending on the evaluation of a variety of factors. Third, assessment of future risk for acquisition of hepatitis A virus (HAV) should direct initiation (or completion) of hepatitis A vaccine to prevent future infection.

Assessment for Hepatitis A Postexposure Prophylaxis

Administering postexposure prophylaxis to prevent hepatitis A should occur if the following four criteria are met.

  1. The source of the exposure (index case) had serologic confirmation of acute hepatitis A, as documented by a positive IgM anti-HAV test result.
  2. The type of contact with the source was a known risk for HAV transmission (Figure 1).
  3. The contact occurred when the source was infectious. In persons with hepatitis A, peak infectivity occurs during the 2-week period before the onset of jaundice (or 2 weeks before the increase in liver enzyme levels), when the concentration of HAV in stool is highest. The concentration of virus in stool declines substantially after jaundice appears. Although virus in stool can persist at low levels for another 1 week, exposure to the source during the 2 weeks prior to the onset of jaundice is considered the period when transmission is most likely to occur.
  4. The evaluation for postexposure prophylaxis takes place within a time frame whereby postexposure prophylaxis would provide benefit. Use of either IG or hepatitis A vaccine for postexposure prophylaxis is not recommended if more than 2 weeks have elapsed from the last exposure to the infectious source[1,2]. In addition, postexposure prophylaxis is not indicated if the exposed individual has received one or more doses of hepatitis A vaccine at least one month prior to the exposure[1,2].

Recommendations for Postexposure Prophylaxis

Historically, only IG was recommended for HAV postexposure prophylaxis, whereas HAV vaccine was recommended primarily for pre-exposure prophylaxis. In October 2007, the US Advisory Committee on Immunization Practices (ACIP) updated their guidelines[3] to include HAV vaccine in the postexposure prophylaxis recommendations. The revision in the ACIP guidelines was based on results of a randomized, double-blind non-inferiority trial that demonstrated comparable efficacy of HAV vaccine and IG when administered within 14 days of exposure to HAV in healthy persons 12 months to 40 years of age[4]. Assuming IG is 90% efficacious in preventing HAV, the vaccine was estimated to have 86% efficacy in preventing symptomatic HAV infection (95% CI 73 to 93%)[4]. The vaccine has a number of advantages for postexposure prophylaxis when compared with IG, including induction of active immunity that provides long-term protection, greater ease of administration, higher patient acceptability, and widespread availability. Screening of the exposed individual for HAV immunity by measuring serum antibody to HAV before administering HAV vaccine or IG is not recommended for two reasons. First, serologic screening is generally not cost-effective in this setting. Second, waiting for the results of screening can delay vaccine or IG administration and thus reduce the efficacy of postexposure prophylaxis.

2007 ACIP Recommendations for Postexposure Prophylaxis

The 2007 ACIP postexposure prophylaxis recommendations state that persons recently exposed to hepatitis A and who have not previously received HAV vaccination should be administered either a single-dose of HAV single-antigen vaccine or immune globulin (IG) as soon as possible, and within 14 days after exposure[3]. No information exists regarding the efficacy of IG or vaccine if administered >2 weeks after exposure. These guidelines, however, stratify the recommendations based on the patient population exposed:

  1. For healthy persons aged 12 months-40 years of age, single antigen HAV vaccine is preferred
  2. For persons older than 40 years of age, IG is preferred, but HAV vaccine can be used if IG cannot be obtained; and
  3. For children younger than 12 months, immunocompromised individuals, persons with a diagnosis of chronic liver disease, and persons with a contraindication to vaccine, the use of IG is recommended.

For groups other than healthy persons 12 months-40 years of age, the ACIP recommendation to use IG takes into account the lack of data on vaccine performance in these groups, as well as the greater risk of severe consequences of HAV among older patients and patients with chronic liver disease. Persons who receive HAV vaccine for postexposure prophylaxis should receive the second dose at the appropriate licensed schedule to complete the series. In addition, for persons receiving IG postexposure prophylaxis and for whom HAV vaccine is recommended for long-term HAV protection, the first dose of the HAV vaccine series should be given at the same time the IG is given, though at a separate anatomic site[3].

Administering HAV Vaccine for Postexposure Prophylaxis

When using HAV vaccine in the postexposure prophylaxis setting, any of the single-antigen licensed HAV vaccines can be used, but the vaccine series should be given at the age-appropriate schedule and dose (Figure 2). Hepatitis A vaccine should be administered as an intramuscular dose in the deltoid muscle. Two inactivated hepatitis A vaccines are available in the United States (Havrix and Vaqta)[1]. The updated recommendations for use of hepatitis A vaccine alone for postexposure prophylaxis do not apply to the combination hepatitis A/hepatitis B vaccine (Twinrix) because no data exist regarding the performance of the combination vaccine for prophylaxis after exposure to HAV[6]. The concentration of HAV antigen in the currently available combination vaccine formulation is half that included in the single-antigen vaccine available from the same manufacturer.

Administering Immune Globulin (IG) for Postexposure Prophylaxis

When IG is administered, it should be given as a a single intramuscular dose (0.02 mL/kg) in the deltoid or gluteal muscle, as these sites can accommodate a large volume injection with a needle length appropriate for the person's age and size. If administered within 2 weeks following an exposure to HAV, IG is more than 85% effective in preventing hepatitis A [1,2]. Efficacy is greatest when IG is administered early in the incubation period. Hepatitis A vaccine and IG can be administered simultaneously, but they should be given at separate anatomic injection sites. In general, IG does not interfere with the immune response to inactivated vaccines; it can, however, interfere with the response to many live, attenuated vaccines, and appropriate precautions should be taken to have a sufficient interval between IG administration and certain live vaccines [1,2]. Although IG is made from pooled human plasma, the preparation of IG includes multiple steps to ensure the final product does not contain any potentially infectious pathogens. Indeed, no instances of transmission of HIV, hepatitis B virus, hepatitis C virus, or other viruses have been reported with the intramuscular use of IG and no significant adverse effects were noted in clinical trials[7]. In addition, pregnant women and women who are nursing can safely receive IG.

Completing Hepatitis A Vaccine Series for Long-Term Protection

As noted, persons receiving hepatitis A vaccine for postexposure prophylaxis should complete the hepatitis A vaccine series to provide long-term protection against HAV infection. In addition, individuals who receive IG for postexposure prophylaxis and for whom hepatitis A vaccine is also recommended (for other reasons) should receive the hepatitis A vaccine series. Further details regarding hepatitis A immunization, including indications for routine preexposure prophylaxis, are provided in the Hepatitis A Vaccine case in this same Hepatitis A module. Postvaccination testing to determine adequate immune response is not indicated since the vaccine series induces protective antibody levels in 98 to 99% of healthy adults[8,9].

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    Figure 1 - Settings for Consideration of Immunoglobulin (IG) Postexposure Prophylaxis Against Hepatitis A Infection

    Adapted from CDC. Prevention of hepatitis A through active or passive immunization: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 1999;48(RR-12):1-37.

    Figure 1
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    Figure 2 - Hepatitis A Vaccines Figure 2