Significance of Fas antigen-mediated apoptosis in human fulminant hepatic failure

OBJECTIVE: The aim of this study was to elucidate the role of apoptosis in human fulminant hepatic failure. We studied the expression of Fas antigen o n liver tissues, Fas ligand in lymphocytes, and soluble Fas ligand in patie nts' serum. METHODS: On finding apoptotic cells in fulminant hepatic failure liver, we first examined them using the TUNEL method. Subsequently, the expression of Fas was studied by immunostaining. Simultaneously, Fas ligand presenting o n both liver-infiltrated cells and peripheral lymphocytes was studied by re verse transcription-polymerase chain reaction, and soluble Fas ligand in se ra was measured by ELISA. RESULTS: By using the TUNEL method, we first demonstrated that many apoptot ic cells existed in fulminant hepatic failure bat not in normal ones. Our i mmunohistochemistry study showed that many hepatocytes in fulminant hepatic failure strongly expressed Fas. In addition, Fas ligand on both liver-infi ltrating lymphocytes and peripheral lymphocytes in fulminant hepatic failur e patients was detected. The serum level of soluble Fas ligand was signific antly increased in fulminant hepatic failure (mean value, 2.91 ng/ml in ful minant hepatic failure [n = 10], 1.62 ng/ml in acute hepatitis [n = 10], an d 0.27 ng/ml in healthy controls [n = 10]). Furthermore, this serum level o f sFas ligand was significantly associated with prothrombin time both in ac ute hepatitis and fulminant hepatic failure. CONCLUSIONS: The present results indicate that Fas-mediated apoptosis may b e one of the triggers for che induction of fulminant hepatic failure. (C) 2 000 by Am. Cell. of Gastroenterology.