In patients with autoimmune chronic
liver disease, a defect in the regulatory system of the immune response allows proliferation of clones of cells reacting with hepatocyte
antigens. Identification of these target
antigens, their isolation, and purification will allow further study of the nature of the immune
diathesis and permit development of specific
therapy designed to eliminate the malregulated clones of immunocytes. The mechanisms resulting in hepatocyte damage during chronic HBV
infection are more complex. Both lobular focal and periportal piecemeal
necrosis of hepatocytes is seen. Current evidence is consistent with the view that focal
necrosis represents T-cell lysis of hepatocytes containing replicating virus, whereas piecemeal
necrosis is a reflection of an autoimmune response to native liver membrane
antigens, initiated by viral replication. The latter response would be expected to be greatest during viral replication, but because of the increase in suppressor T-cell concentrations that occurs at this time, the liver membrane antibody response is largely suppressed. When viral replication ceases, in patients with normal suppressor cells, the liver membrane antibody response is suppressed. In some patients, suppressor cells are relatively reduced and the liver membrane antibody response continues after cessation of viral replication. At this stage, the composition of the inflammatory infiltrate in the liver is similar to that seen in autoimmune (lupoid)
chronic active hepatitis. The destruction of hepatocytes containing integrated HBV-
DNA is probably dependent on an immune response to HBs
antigen. Failure of this elimination process, for immunogenetic or environmental reasons, results in persistence of clones of cells from which malignantly derived cells may ultimately arise. Adequate
therapy of this condition must not only stop the replication of the virus, thereby reducing hepatic inflammatory activity, but eliminate clones of cells containing integrated HBV-
DNA so that the danger of malignant transformation of hepatocytes is removed.