Immunopathology of hepatitis B antigen positive and negative active chronic hepatitis.

Evidence is presented to suggest that an auto-immune response to a liver-specific lipoprotein antigen on the surface of hepatocytes is responsible for the progressive liver damage in active chronic hepatitis, and that in many cases infection with the hepatitis B virus is important in the initiation of the disease process. B cells appear to play a major role in the auto-immune response and may be activated by T cells reacting with viral antigens on the surface of infected hepatocytes. A postulated defect in humoral antibody production in HBAg-positive cases allows continued reinfection of the liver by the hepatitis B virus, persistence of a virus-directed T cell response and constant activation of B cells reacting with the liver-specific lipoprotein. In the HBAg -negative group the disease is also, in many cases initiated by an acute hepatitis, but here the auto-immune response continues after elimination of the virus because of a defect in the suppressor function of T cells which fail to turn off the autoreactive B cells. The histocompatibility antigen, HL-A8, may be a marker for such a defect in suppressor T cells - its increased frequency in active chronic hepatitis is restricted to the HBAg-negative cases. Finally, the hypothesis suggests how specific immunotherapy, either antibody to HBAg or Transfer Factor, could be given to correct the basic defects which lead to persistence of the auto-immune process.