Significant role of apoptosis in type-1 autoimmune hepatitis.

We used the terminal deoxyribonucleotidyl transferase-mediated deoxyuridine triphosphate-digoxigenin nick-end labeling (TUNEL) method to detect apoptosis, and immunohistochemical staining for molecules related to apoptosis, a marker of cell proliferation, and surface markers of lymphocytes to examine 20 patients with autoimmune hepatitis (AIH). Confluent hepatic necrosis was frequently found, in which rosette formation of hepatocytes and ductular proliferation were common. TUNEL staining and staining for Lewis Y antigen, Bax protein, and Fas antigen were found in biliary epithelial cells in bile ducts and proliferating atypical bile ductules in regions of confluent necrosis with severe lymphocytic infiltration. TUNEL staining and staining for Lewis Y antigen and Bax protein were found in rosette-forming hepatocytes. Many hepatocytes in lobules without injury were stained for proliferating cell nuclear antigen (PCNA). bcl-2 oncoprotein was found in many lymphocytes surrounding proliferating atypical bile ductules and rosette-forming hepatocytes in regions of confluent necrosis, in which CD20 and OPD 4 were found. Apoptosis of both hepatocytes in rosette arrangement and biliary epithelial cells in bile ducts and proliferating atypical bile ductules may play a role in progression of AIH as well as confluent hepatic necrosis.