Hepatocyte apoptosis is a pathologic feature of human alcoholic hepatitis

Background/Aims: The pathogenesis of alcoholic hepatitis (AH) remains poorl y understood. Although apoptosis is now recognized as a mechanism of liver injury, the extent and mechanisms of apoptosis in human AH remain unknown. Thus, our aims were to quantify hepatocyte apoptosis in patients with AH, c orrelate it with disease severity, and identify the mechanisms of apoptosis induction. Methods: Hepatocyte apoptosis was assessed in 26 patients with AH and 27 co ntrols without liver disease using the TUNEL assay and immunohistochemistry for activated caspase 3, Liver specimens were also graded for disease seve rity. The expression of the death receptors, Fas and tumor necrosis factor- alpha receptor 1 (TNF-R1), was assessed by immunohistochemistry. Results: In contrast to normal livers, TUNEL- and caspase 3-positive hepato cytes were readily observed in the livers of patients with AH. In the AH gr oup, hepatocyte apoptosis was significantly higher in patients with a serum bilirubin of >3 mg/dl, Apoptosis was also greater in grade 4 steatohepatit is. The Fas receptor was strongly expressed in hepatocytes in AH, but not i n normal livers; the TNF-R1 expression was comparable in both groups. Conclusions: The present results demonstrate that hepatocyte apoptosis is s ignificantly increased in human AH and justify therapeutic strategies aimed at inhibiting apoptosis in this disease. (C) 2001 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights rese rved.