Is the hepatitis A vaccine an alternative to immune globulin for postexposure prophylaxis?

Hepatitis A is a reasonable alternative to immune globulin. Advantages of the vaccine include the likelihood of subsequent immunity, the fact that it is not a blood product, a less painful injection, and its wider availability, while a disadvantage is higher cost (although the authors argue that the cost of immune globulin is nearly as high as that of vaccine now). (LOE = 1b)

Victor JC, Monto AS, Surdina TY, et al. Hepatitis A vaccine versus immune globulin for postexposure prophylaxis. N Engl J Med 2007;357(17):1685-1694.  [PMID:17947390]

Randomized controlled trial (double-blinded)

Industry + govt

Unconcealed

Outpatient (any)

This study, set in Kazakhstan, randomized 4524 patients who had been exposed to hepatitis within the past 14 days to receive either hepatitis A vaccine (VAQTA, Merck) or immune globulin (0.02 mL/kg). Infants younger than 2 years and adults older than 40 years were excluded, as were patients with liver disease or a history of previous hepatitis A infection or immunization. The treating physicians knew which interventions were given, a potential bias although it is unclear how this might have influenced the results. Generally the lack of blinding favors the groups receiving the intervention. Patients were monitored for hepatitis A IgM antibodies 4 weeks and 8 weeks after exposure and were also told to contact the investigators if they developed symptoms. The primary end point of clinical hepatitis A infection was defined as positive IgM, serum alanine aminiotransferase at least twice the upper limit of normal, and at least one typical sign or symptom of hepatitis. Groups were balanced at the start of the study and the authors reported both per-protocol and modified intention-to-treat analysis. Although 4524 patients were initially randomized, approximately 75% in each group were found to be immune or already have contracted hepatitis A based on their baseline IgM. This left 740 patients in the vaccine group and 674 in the immune globulin group (the modified intention-to-treat analysis groups). Clinical Hepatitis A was diagnosed in 3.5% of those given the vaccine and 2.7% of those given immune globulin (relative risk = 1.32; 95% CI, 0.69 to 2.5). There were no serious adverse events attributed to the immunization or to the immune globulin.