HEPATIC-FAILURE AND LIVER-CELL DAMAGE IN ACUTE WILSONS-DISEASE INVOLVE CD95 (APO-1 FAS) MEDIATED APOPTOSIS/

Wilson's disease can result in fulminant liver failure due to hepatic copper overload. The CD95 system mediates apoptosis and has been demon strated to be involved in liver disease. In this study CD95 mediated a poptosis was investigated in patients with fulminant hepatic failure i n the course of Wilson's disease and in an in vitro model of copper tr eated human hepatoma cells. In patients, hepatic expression of CD95 an d CD95L mRNA and apoptosis were detected. Copper overload in vitro res ulted in hepatocytic apoptosis which could be reduced with a neutraliz ing anti-CD95L antibody. Copper treatment of hepatocytes results in ac tivation of the CD95 system and induction of apoptosis which is operat ive during the course of hepatic failure in acute Wilson's disease.