Apoptotic mechanisms in fulminant hepatic failure: potential therapeutic target.

Pathogenesis of fulminant hepatic failure (FHF) in nonacetaminophen etiology is not elucidated. We have investigated the significance of tumor necrosis factor (TNF) type-I receptor (TNF-R1) and Fas receptor (CD95, APO-1) in FHF.,Liver biopsy samples were obtained from 14 FHF patients. Liver tissue samples of 10 patients with acute viral hepatitis (AVH) and 10 cases who died, unrelated to liver disease served as tissue biopsy controls. Immunohistochemical methods were employed to analyze expression of TNF-R1 and Fas expression in hepatocytes.,Immunohistochemical analysis revealed high expression (P<0.001) of Fas and TNF-R1 in FHF cases in relation to AVH cases. This expression was more in cytoplasm of apoptotic hepatocytes than viable swollen hepatocytes and this correlated with the extent of hepatocyte apoptosis. The mean apoptotic index was significantly (P<0.001) higher in FHF in relation to AVH.,Enhanced expression of TNF-R1 and Fas receptors on the apoptotic hepatocytes suggest that both may be involved in the pathogenesis of FHF and seem to be potential therapeutic target.