Liver transplantation is the only effective treatment for potentially fatal cases of fulminant hepatic failure. However, it is very difficult to predict which cases will be fatal. The mortality may depend on alternative medical therapies. According to a nationwide survey of patients with fulminant hepatic failure presenting with encephalopathy of a coma grade greater than 11 within 8 weeks from the first symptoms of illness with a prothrombin time less than 40% of normal value, there were 93 patients in 311 hospitals between January and December 1998 in Japan. During this period, there were 11 patients with late-onset hepatic failure. The etiology was HAV infection in 4%, HBV infection in 44%, and nonA-nonB in 41 %. Specific therapies were intensively used in all patients. The mean survival rate was 44 %, with differences depending on the etiology. Six patients underwent liver transplantation, and 5 survived. In animal experiments, sinusoidal fibrin deposition caused massive liver necrosis. Activation of Kupffer cells and hepatic macrophages was a major contributing factor of this development. There were different mechanisms of such fibrin deposition. Tumor necrosis factor-a and superoxide anions released from hepatic macrophages after endotoxin administration destroyed endothelial cells, and then coagulopathy occurred in the sinusoids in rats given Propionibacteriom acnes, while a tissue factor from Kupffer cells played that role in rats undergoing partial hepatectomy. The prognosis of fulminant hepatic failure may depend on the etiology. The indication for liver transplantation for this disease must be carefully decided by analyzing the etiology, pathological conditions, and response to therapies in each case.