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C D95 (APO-1/Fas) belongs to the subfamily of death receptors among the tumor necrosis factor/ nerve growth factor receptor superfamily. 1 CD95 plays an important role in liver homeostasis. 2 Hepatocytes express high amounts of CD95 and are very sensitive toward CD95 triggering. 3,4 Mice injected with agonistic anti-CD95 antibody rapidly die of liver failure. 5 CD95-mediated apoptosis is involved in a broad spectrum of human liver diseases, including acute liver failure. 6 In vivo silencing of the CD95 gene via small, interfering RNA protects mice from liver failure as well as from fibrosis in a model of autoimmune hepatitis. 7 A key event of CD95 signaling is the formation of a multimeric complex of proteins called death-inducing signaling complex (DISC). Two different pathways are described downstream of CD95. In type I cells, the death signal is propagated by a cascade that is initiated by the activation of large amounts of caspase-8 at the DISC and subsequent activation of downstream caspases. 8 In type II cells, including hepatocytes, DISC formation is weak, and the Heidelberg (M.M. and P.K.).

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