lewis-x-antigen and Hepatitis--Alcoholic

Although human and experimental studies have shown that apoptosis plays a role in hepatocyte death in alcoholic liver disease, its clinical and biological significance has not been investigated in alcoholic hepatitis (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.. The hepatocyte apoptotic index was determined using a double in situ transferase-mediated dUTP nick end (TUNEL) and CD15 (neutrophils) labelling on 35 liver biopsies from patients with AH lesions of different severities. The specificity of TUNEL labelling for apoptosis was monitored both by morphology and fractin (a caspase actin cleavage site) immunostaining.. The hepatocyte apoptotic index ranged from 0.3 to 28% and was related 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.. This suggests that hepatocyte apoptosis could be a therapeutic target to treat or to prevent alcoholic hepatitis in cirrhotic patients. Co-localization of apoptotic hepatocytes with neutrophils and the strong quantitative correlation would suggest an apoptosis dependent transmigration of neutrophils.

Topics: Actins; Adult; Aged; Apoptosis; Case-Control Studies; DNA Fragmentation; Female; Hepatitis, Alcoholic; Hepatocytes; Humans; In Situ Nick-End Labeling; Lewis X Antigen; Male; Middle Aged; Neutrophils; Peptide Fragments

Apoptosis is a type of cell death which is clearly distinguishable from necrosis in its morphological and biochemical features. To clarify the role of apoptosis in alcoholic liver injury, we investigated the expression of apoptosis-related Lewis(Le)(y) antigen by immunohistochemistry in liver samples from patients suffering from alcoholic liver disease. Liver biopsy samples were taken from 20 patients who drank more than 80 g of ethanol per day on average. Indirect immunohistochemical staining was carried out using anti-cytokeratin and anti-Le(y) antibodies. To examine the relationship between Mallory bodies and apoptosis, double staining was performed using both antibodies. In alcoholic hepatitis, many Mallory bodies were stained with anti-cytokeratin antibody in hepatocytes of the centrilobular area. Le(y) antigen was also detected in hepatocytes in the same area. Immunohistochemical double staining showed that some of the hepatocytes containing Mallory bodies were stained with anti-Le(y) antibody. Few hepatocytes expressing Le(y) antigens, however, were observed in other types of alcoholic liver disease, including steatosis, fibrosis and cirrhosis. From these results, it is suggested that apoptosis may also be involved in alcoholic hepatitis and that hepatocytes containing Mallory bodies can be eliminated by apoptosis.

Topics: Apoptosis; Hepatitis, Alcoholic; Humans; Immunohistochemistry; Lewis X Antigen; Liver Cirrhosis