1. To determine the role of immunogenetic factors (such as polymorphisms of the Major Histocompatibility Complex) in the outcome of hepatitis B virus infection
2. To determine the role of immunogenetic factors in the response to interferon therapy for chronic hepatitis B virus infection.
3. To establish a clinical database of subjects with viral hepatitis with a library of genomic DNA and serum samples from these subjects.
A collaborating network of 9 European hepatology centres has been created to investigate the problem of hepatitis B virus infection. Although the majority of subjects exposed to HBV infection recover spontaneously, 5 - 10% develop persistent infection with concomitant sequelae. Persistent infection may be cleared with interferon therapy in up to 40% of patients.
The role of immunogenetic factors will be determined for the prediction of the outcome of HBV infection and in the response to interferon therapy. A large, molecular based, MHC disease association study will be conducted to determine MHC class I & II alleles associated with persistent HBV infection in Europe. Further case-control studies will be performed using candidate polymorphisms determined either through genomic scanning or scientific reasoning. The network of centres will be used to recruit patients and collect clinical samples. Immunogenetic analyses will be performed at St Mary's Hospital, London using sequence specific PCR analysis and dot-blot hybridization techniques.
Clinical and laboratory data will collected from all patients recruited to the study and will be used alongside the immunogenetic data to create a logistic regression model of the outcome of HBV infection and interferon therapy. A database of clinical records and an archive of DNA and serum samples will be assembled for this study and further European research.