Immunopathology of chronic viral hepatitis.

This paper reviews the main necro-inflammatory liver lesions observed in chronic viral hepatitis B and their apparent immunological mechanisms. Focal necrosis seems to represent the mechanism for clearance of virus replicating hepatocytes by cytotoxic T lymphocytes under HLA class I restriction and with hepatitis B virus nucleocapsid antigens as target antigen. Piecemeal necrosis involves CD8+ lymphocytes, possibly with hepatocellular membrane autoantigens as target antigen. Confluent lytic necrosis (bridging hepatic necrosis) presumably results from humoral immune mechanisms. Focal necrosis, piecemeal necrosis and confluent lytic necrosis determine the extent of necro-inflammatory activity in liver biopsy specimens, classified as chronic persistent hepatitis (low activity) or chronic active hepatitis (high activity). The extent of necro-inflammatory activity fluctuates during the natural course of chronic viral hepatitis B: from low activity during the viral replicative phase, through high activity in the viral elimination phase, into low activity again in the ensuing viral integration phase. The role of HLA antigens, intercellular adhesion molecules, cytokines and accessory antigen presenting cells is emphasized.