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Effects of Alcohol on HCV Replication and Treatment Response

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Effects of Alcohol on HCV Replication and Treatment ResponseBy Liz Highleyman

It is well known that heavy alcohol consumption can lead to advanced liver disease, including cirrhosis and hepatocellular carcinoma, but the effects of alcohol on hepatitis C virus (HCV) infection and its treatment are not fully understood.As reported in the December 15, 2008 Journal of Infectious Diseases, McCartney from the University of Adelaide in Australia and colleagues conducted a laboratory study to determine the effect of alcohol metabolism on HCV replication and the antiviral activity of interferon.The researchers used Huh-7 cells that allow for in vitro HCV replication and metabolize ethanol via the introduced expression of cytochrome P450 2E1 (Cyp2e1). Cell cultures were exposed to ethanol and "treated" with interferon alfa.Results

Exposing the cells to ethanol (0-100 mmol/L) significantly increased HCV replication. This effect was dependent on Cyp2e1 expression and alcohol-metabolized oxidative stress. This was demonstrated by the fact that the antioxidant N-acetylcysteine blocked the effect. The anti-HCV action of interferon alfa was reduced in the presence of ethanol, most likely via attenuation of Stat1 tyrosine-701 phosphorylation.

"These in vitro results mimic what is often noted clinically," the researchers concluded. "[F]urther dissection of this model system will aid in our understanding of interactions between HCV and alcohol metabolism."These findings serve to underline the recommendation that people with chronic hepatitis C or other types of liver disease should avoid alcohol entirely or consume it only in small amounts.Infectious Diseases Laboratories, Institute of Medical and Veterinary Science, and School of Molecular and Biomedical Sciences, University of Adelaide, Adelaide, Australia; Digestive Diseases Laboratory, Northern Clinical School, University of Sydney, Sydney, Australia; Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX.

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