Recombinant hepatitis B vaccine and the risk of multiple sclerosis: A prospective study. Hernán MA, Jick SS, Olek MJ, Jick H. Neurology 2004;63(5):838-842.
Explanatory note: Hepatitis B virus (HBV) immunization is recommended for all infants, children, adolescents, and high-risk adults in the United States for protection from serious liver disease including liver cancer.
HBV vaccine has been suggested as a cause of demyelinating neurological disorders, such as multiple sclerosis (MS) and Guillain-Barré syndrome. In 2002, the Institute of Medicine (IOM) Immunization Safety Review Committee reviewed the evidence regarding the hypothesis that the hepatitis B vaccine causes demyelinating disorders. The Committee found that evidence of possible biological mechanisms that could produce this effect was weak and concluded that the evidence favored rejection of a causal relationship between the HBV vaccine in adults and MS.
Are some multiple sclerosis (MS) cases associated with HBV vaccination?
This case-control study used data from the General Practice Research Database (GPRD), which includes medical records of more than 3 million people in the United Kingdom. This study only looked at adults.
Of the 713 adults diagnosed with MS between January 1, 1993, and December 31, 2000 in the GPRD, 163 were selected for study. Of these, 11 HBV vaccinated patients were used for analysis. They then compared these 11 cases with a control group of people with no MS diagnosis, which were also in the GPRD, matched on age, sex and medical practice attended.
Immunizations with HBV, tetanus and influenza vaccines were determined from computerized medical records. The immunization records were not verified, however.
This study found that the proportion of cases that received at least one HBV immunization during the 3 years before the date of first symptoms was greater than in controls, suggesting that the risk of MS could be higher for people vaccinated with HBV vaccine than for people not vaccinated against hepatitis B.
Only 11 of the patients with MS in this study (7%) had received HBV vaccine.
The study found no increase in the risk of MS after vaccination against influenza or tetanus.
These study results are consistent with a hypothesis that HBV could increase the risk of MS in a small proportion of the adults who subsequently develop MS. However, the study is based on a very small number of individuals.
This study differs from many other studies, which did not find a relation between HBV vaccine and MS (as reviewed by the IOM Immunization Safety Review Committee).
The present study has serious limitations. Many of the people identified with MS were excluded and there were only 11 cases of MS in the HBV immunized group. In addition, the controls for each case were not matched for whether they had an indication for HBV vaccine (such as being a healthcare worker). This likely would have introduced serious selection bias because, at the time of this study, vaccination against HBV in the United Kingdom was targeted towards people at risk for HBV exposure.
Thus, the findings do not provide convincing evidence to support a hypothesis for an association of HBV vaccine and MS. Other expert groups have interpreted these findings similarly (for example, WHO’s Global Advisory Committee on Vaccine Safety).