Pathogenesis of active chronic hepatitis.

The possible immunological mechanisms involved in the progression from acute type B hepatitis to chronic hepatitis can be summarised as follows: following replication of the virus in the hepatocyte nucleus, the surface coat is added and the virus released from the hepatocyte. T cells recognise the foreign viral antigen on the surface of the liver cells and mount a T cell mediated reaction against infected hepatocytes. They also stimulate B cells to produce antibody to LSP, the ensuing antibody-dependent cell-mediated K cell reaction against normal liver membrane antigens contributing to the hepatocyte necrosis. Released virus stimulates anti-viral antibody production which complexes with the virus, the complex being removed by the reticuloendothelial system. With the removal of virus there is no longer any T cell reaction against the virus or helper effect for anti-LSP production and this, together with a normally functioning suppressor T cell system, leads to cessation of liver cell necrosis and recovery from the episode of acute hepatitis. In HBsAg-positive ACH as a result of a quantitative or qualitative defect in the production of antibody to Dane particles there is a failure to clear the virus, with reinfection of further hepatocytes and continuation of both mechanisms of immunological liver cell damage. In patients progressing to HBsAg-negative ACH, however, anti-viral antibody production is adequate and the virus is cleared. In this group of patients the defect probably lies in suppressor T cell function, which is unable to switch off the autoimmune reaction against LSP. The increased frequency of histocompatibility antigens HLA A1 and B8 and the associated high levels of autoantibodies and anti-viral antibodies suggests that this defect may be genetically inherited.