Clinical and biological relevance of hepatocyte apoptosis in alcoholic hepatitis

Background/Aims: Although human and experimental studies have shown that ap optosis plays a role in hepatocyte death in alcoholic liver disease, its cl inical and biological significance has not been investigated in alcoholic h epatitis (AH),The aim of this study was to quantify hepatocyte apoptosis in AH and to attempt to relate it to the clinical and biological severity of the disease. Methods: The hepatocyte apoptotic index was determined using a double in si tu transferase-mediated dUTP nick end (TUNEL) and CD15 (neutrophils) labell ing on 35 liver biopsies from patients with AH lesions of different severit ies. The specificity of TUNEL labelling for apoptosis was monitored both by morphology and fractin (a caspase actin cleavage site) immunostaining. Results: The hepatocyte apoptotic index ranged from 0.3 to 28% and was rela ted to the severity of alcoholic hepatitis as measured by the Maddrey score (P < 0.05; Mann-Whitney test) while ballooning (which reflects hepatocytes potentially undergoing necrosis) and neutrophil indexes were not. Conclusions: This suggests that hepatocyte apoptosis could be a therapeutic target to treat or to prevent alcoholic hepatitis in cirrhotic patients. C o-localization of apoptotic hepatocytes with neutrophils and the strong qua ntitative correlation would suggest an apoptosis dependent transmigration o f neutrophils. (C) 2001 European Association for the Study of the Liver. Pu blished by Elsevier Science B.V. All rights reserved.