Significance of soluble TNF receptor-I in acute-type fulminant hepatitis

OBJECTIVE: Fulminant hepatitis is associated with apoptosis of hepatocytes, which is mediated via Fas and tumor necrosis factor (TNF) receptors. The c linical significance of apoptotic factors and these receptors was investiga ted in fulminant hepatitis. METHODS: Serum levels of TNF-alpha, soluble TNF receptor-I and -II, soluble Fas antigen, and Fas ligand were measured. Then, the relationships between these parameters and the severity or prognosis of fulminant hepatitis were studied. RESULTS: Serum levels of TNF-or, soluble TNF receptor-I, and soluble TNF re ceptor-II were increased in acute-type fulminant hepatitis. In particular, soluble TNF receptor-I was significantly higher than in patients with subac ute-type fulminant hepatitis, severe acute hepatitis, acute hepatitis, or h ealthy controls. The soluble TNF receptor-I level continued to increase or remained high in patients who died of acute-type fulminant hepatitis, and e ight of nine patients had a level >10 ng/ml. In contrast, the soluble TNF r eceptor-I level remained <10 ng/ml in survivors. Soluble Fas and soluble Fa s ligand levels tended to increase in all types of acute liver disease and were not specific to fulminant hepatitis. CONCLUSION: Our findings suggested that monitoring the soluble TNF receptor -I level may help to assess the prognosis of acute-type fulminant hepatitis and that TNF might be associated with massive hepatic necrosis. (C) 2000 b y Am. Cell. of Gastroenterology.