Alcohol consumption induces hepatocyte apoptosis in patients with chronic hepatitis C infection.
BACKGROUND
Epidemiological studies have established that heavy alcohol consumption in persons with chronic hepatitis C infection is associated with advanced liver disease, including cirrhosis. The cellular mechanisms underlying this process, which appear to occur over decades, are unknown. Increased hepatocyte apoptosis has been observed in association with hepatitis C infection. The aim of this study was to evaluate the relationship between alcohol consumption and hepatocyte apoptosis in hepatitis C-infected patients.


METHODS
Liver tissue from 20 hepatitis C-infected patients with variable alcohol consumption, and 10 normal control subjects was examined for hepatocyte apoptosis, proliferation and bcl-2 expression.


RESULTS
Hepatocyte apoptosis was significantly greater in hepatitis C-infected patients than in controls. In hepatitis C-infected patients, significantly more hepatocyte apoptosis was seen in those consuming at least 30 g per day of alcohol compared with those drinking less than 10 g daily. Bcl-2, an inhibitor of apoptosis, was not detected in liver tissue from patients with the highest ethanol intake and rate of hepatocyte apoptosis. In contrast, patients drinking lesser amounts of ethanol had lower rates of hepatocyte apoptosis and more frequent bcl-2 expression.


CONCLUSIONS
This study confirms that both hepatitis C infection and ethanol consumption induce hepatocyte apoptosis in humans. Ethanol-induced hepatocyte apoptosis has previously been shown only in animal models of alcohol-related liver injury. The precise role of apoptosis in the pathogenesis of hepatitis C-related liver injury remains unclear, but its induction may be related to downregulation of bcl-2 expression associated with ethanol consumption.
Department of Medicine, Monash Medical Centre, Melbourne, Australia.
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Pianko
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Patella
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Sievert
D000328:Adult; D000428:Alcohol Drinking; D017209:Apoptosis; D005260:Female; D019254:Genes, bcl-2 / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000473:pathology*; D022781:Hepatocytes / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies