Apoptosis in acute hepatic failure: histopathological study of human liver tissue using the tunel method and immunohistochemistry

The role of apoptpsis in the occurrence of massive or submassive liver cell death was investigated. Of liver tissues removed from 49 autopsy cases of acute hepatic failure, 26 cases were fulminant hepatic failure (FHF), 13 were subacute hepatic failure (SAHF) and the remaining 10 were acute-on-chronic hepatic failure (AoCHF). Eleven cases were associated with HBV infection, 2 with HCV, 5 with non-A non-B hepatitis, 4 with drug medication and 4 with autoimmune disorder, while the etiology of 23 cases remained unknown. Examinations by the TUNEL method and immunohistochemistry using anti-Fas, -Bax, and -Bcl-2 antibodies were conducted. Most of the FHF and AoCHF cases and half of the SAHF cases showed massive or submassive hepatic lobular injury histopathologically. TUNEL positive cells were observed frequently, and the grade of lobular injury showed significant correlation with the frequency of TUNEL-positive liver cells. Bax and Fas were expressed on the remaining liver cells, while Bcl-2 was seen on the infiltrating lymphocytes. The frequency of TUNEL-positive liver cells showed a significant correlation with Bax expression and the grades of inflammatory cell infiltration, but a poor correlation with Fas and Bcl-2 expression. The results of the present study suggested that apoptosis plays an important role in massive and submassive hepatic cell death. Fas and Bcl-2 might not be involved in the apoptosis of liver cells, but the findings suggested that Bax might play a role in inducing liver cell apoptosis, though the mechanism could not be explained.