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New Recommendations for the Prevention of Hepatitis A
Abstract & Commentary
By Stan Deresinski, MD, FACP
Clinical Professor of Medicine, Stanford University; Associate Chief of Infectious Diseases, Santa Clara Valley Medical Center.
Dr. Deresinski reports no financial relationship relevant to this field of study. This article originally appeared in the December 2007 issue of Infectious Disease Alert. It was peer reviewed by Connie Price, MD, Assistant Professor, University of Colorado School of Medicine. Dr. Price reports no financial relationship relevant to this field of study.
Synopsis: Low rates of hepatitis A in both groups indicate that hepatitis A vaccine and immune globulin provided good protection after exposure.
Sources: Victor JC, et al. Hepatitis A vaccine versus immune globulin for postexposure prophylaxis. N Engl J Med. 2007;357:1685-1694; CDC. Update: Prevention of hepatitis A after exposure to hepatitis A virus and in international travelers. Updated recommendations of the Advisory Committee on Immunization Practices (ACIP). 2007;56:1080-1084. Available at www.cdc.gov.
Previously, the recommendation in the United States for post-exposure prophylaxis of hepatitis A virus (HAV) infection has consisted of the administration of a single dose of immune serum globulin (ISG). While some other countries recommended the use of HAV vaccine for this purpose, the evidence to support this stance had been judged to be inadequate. New data, however, have now led to a change in recommendations in the United States.
Victor and colleagues randomized household and day-care center contacts of individuals with acute hepatitis A virus (HAV) infection who were 2 to 40 years of age to receive, within 14 days after exposure, either a single dose of HAV vaccine or of immune serum globulin. Of the 1414 subjects who were susceptible to HAV infection, 1090 were included in the final analysis of this study performed in Kazakhstan. The mean age of the subjects was 12 years and the mean interval from exposure to prophylaxis receipt was 18 days.
Laboratory-confirmed symptomatic HAV infection occurred in 25 (4.4%) of the vaccine recipients and in 17 (3.3%) of those given ISG (relative risk, 1.35; 95% CI, 0.70 to 2.67), thus meeting pre-set criteria for non-inferiority of vaccine prophylaxis. It is noted by Victor et al, however, that at all study points examined, infection rates for vaccine recipients were higher than those observed in those given ISG. Nonetheless, "the risk of infection in the vaccine group was never more than 1.5% greater than that in the immune globulin group." These results have led to a change in the APIC and CDC recommendations for post-exposure prophylaxis of HAV infection, as well as for prophylaxis in the international traveler, as discussed below.
The results of this randomized trial fill in a data gap, which has allowed the CDC, upon the advice of APIC, to provide updated recommendations. It must be stressed, however, that the changes only strictly apply to the age cohort included in the study, those 2- to 40-years-old. There is no comparably reliable data that might apply to younger or older individuals, or to individuals who are immunocompromised. As a consequence, the recommendations state that "decisions to use vaccine or ISG should take into account patient characteristics associated with more severe manifestations of hepatitis A, including older age and chronic liver disease." It must also be recognized that, although vaccination efficacy was not inferior to that of ISG, according to preset criteria, the overall data did suggest that ISG "performed modestly better than vaccine." Nonetheless, the drawbacks to ISG use, including the temporary nature of the protection provided, the pain associated with injecting the large volume often required, limitations in product supply, and the concerns of some about safety, make the vaccine an attractive alternative.
The bottom line is that the updated recommendations state that "Persons who recently have been exposed to HAV and who have not previously received hepatitis A vaccine should be administered a single dose of single-antigen vaccine or ISG (90.02 mL/kg) as soon as possible." Note the stress on the "single-antigen vaccine" — this is a consequence of a lack of data regarding the efficacy of the HAV-HBV combined vaccine, which contains a smaller amount of HAV antigen. For those 12 months to 40 years of age, "single-antigen hepatitis A vaccine, at the age-appropriate dose, is preferred to IG." For those > 49 years of age, IG is preferred. IG should be used for children < 12 months of age, immunocompromised persons, persons with known chronic liver disease, and in those in whom the vaccine is contraindicated. The efficacy of either vaccine or ISG, when administered more than 2 weeks after exposure, remains unknown.
The standard recommendation for travelers to countries with high or intermediate HAV endemicity has been the administration of the vaccine. However, it was also recommended that individuals traveling to an area of high endemicity less than 4 weeks after the initial vaccine dose also be considered for receipt of ISG. The updated recommendations now state that hepatitis A single-antigen vaccine alone can be recommended for travelers < 40 years of age at any time prior to departure. For optimal protection, older adults, immunocompromised individuals, and those with chronic medical conditions, including chronic liver disease, should also receive ISG (0.02 mL/kg) at a separate injection site. For those < 12 months of age, or those who refuse vaccine or are allergic to it, a single dose of ISG will provide protection for up to 3 months. If travel is to last > 2 months, the dose of ISG should be 0.06 mL/kg, and dosing should be repeated if travel time exceeds 5 months.