Objective: To review two main issues concerning the hepatitis B vaccine: (1) the management of unresponsive subjects and (2) the need for routine booster doses.
Data sources: Pertinent literature identified via MEDLINE (1980-1996) search as well as references cited in published articles.
Data synthesis: The optimal procedure for management of subjects unresponsive to hepatitis B vaccine has not been well established. Most unresponsive subjects are not absolute nonresponders, since most of them can develop protective concentrations of antibodies to hepatitis B surface antigen (anti-HBsAg) after hepatitis B revaccination, consisting of a fourth or a fifth dose or a new complete course of immunization. In subjects who do not respond to the hepatitis B vaccine after four or more injections, the benefits of the combination of cytokines (e.g., interferon-alfa, interleukin-2 [aldesleukin]) and vaccine have not been clearly shown. There are two main opinions regarding the need for routine booster doses. Experts from the US, claiming long-term protection from immunologic memory, suggest delaying booster doses for at least a decade after vaccination in subjects with normal immune status. Furthermore, postvaccination antibody testing should be restricted only to high-risk subjects. Once a vaccinated subject has responded satisfactorily, further antibody tests are unnecessary. Only hemodialysis patients should be tested annually for adequate antibody concentrations and the booster dose administered when concentrations decline to less than 10 IU/L. Experts from Europe suggest that vaccine-induced antibody responses should be assessed in all subjects and booster doses administered at intervals, with the theory being that protection correlates with the presence of antibody. However, indications about appropriate timing for booster doses and target titers of anti-HBsAg remain controversial.
Conclusions: It is possible to obtain seroconversion in nonresponders by using variations in vaccination strategies (i.e., > 3 doses, double amounts of HBsAg). Adjuvants such as interferon-alfa or aldesleukin are of limited use. The opinions of American experts regarding routine booster doses, as expressed by the statement of the Immunization Practices Advisory Committee, seem to be well defined and helpful to clinicians trying to resolve controversies for individual patients. The opinions of the European experts are not unanimous and are sometimes impractical. A consensus conference is needed.