[Induction and pathogenesis of chronic hepatitis experimentally induced in rabbits (author's transl)]

Studies of recent years have focussed on the immunopathogenesis of chronic liver diseases. Long-term immunization of rabbits with human liver proteins leads to liver lesions typical for human CAH. Delayed hypersensitivity against rabbit liver proteins, tested by skintest, correlated with the morphological changes of the liver. Circulating autoantibodies to liver specific protein, circulating immune complexes and IgG fixed in vivo to isolated hepatocytes could be observed before the liver lesions had developed histologically. The main target antigen in experimentally induced CAH seems to be an organ-specific but species-crossreacting macrolipoprotein with a molecular weight above 1 million, which is localized on the outer surface of the hepatocyte membrane. The liver specific protein (LSP) contains species-specific and non-species-specific determinants. Autoantibodies to non-species-specific determinants of LSP could only be detected in animals which had already developed CAH. Thus experimentally CAH in rabbits may be induced by the loss of tolerance to non-species-specific determinants of the LSP complex. Cell mediated and humoral immunity to LSP in man is found in HBsAg positive and HBsAg negative inflammatory liver diseases. Thus experimental CAH in rabbits seems to be a model for virus-induced and non-virus-induced chronic inflammatory liver diseases.