Clinical

Alcohol enhances hepatitis C virus replicon expression

Last Updated: 2003-07-22 15:14:00 -0400 (Reuters Health)

By Will Boggs, MD

NEW YORK (Reuters Health) - Alcohol enhances the expression of hepatitis C virus (HCV) replicons and interferes with the anti-HCV effects of interferon alfa (IFNa), according to a report in the July issue of Hepatology.

Alcohol consumption accelerates liver damage and reduces the therapeutic response to IFNa in patients infected with HCV, the authors explain, but whether alcohol enhances HCV replication and promotes HCV disease progression was unknown.

Dr. Wen-Zhe Ho from The Children's Hospital of Philadelphia, Pennsylvania and associates examined the effects of alcohol on HCV RNA expression in replicon-containing hepatic cells and the mechanisms behind those effects.

"Although the HCV replicon system mimics only some aspects of HCV replication," the investigators explain, "this cell system provides an important means of investigating viral RNA and protein synthesis and of characterizing those factor(s) that regulate HCV RNA expression."

In cell cultures, alcohol increased the expression of HCV RNA in a concentration-dependent fashion, the authors report, and increases the expression of NS5 protein, which plays a critical role in HCV replication. Alcohol also significantly attenuated the anti-HCV effects of IFNa in culture.

Several experiments demonstrated that alcohol activates nuclear factor kappa B (NFkB), an important transcriptional nuclear factor that controls viral replication and cytokine production.

Naltrexone, an opiate receptor antagonist, inhibited alcohol-induced activation of the NFkB promoter and reversed alcohol's enhancement of HCV RNA expression, the researchers note. Pretreatment of cells with inhibitors of alcohol dehydrogenase and acetaldehyde dehydrogenase also attenuated the alcohol-induced increase of HCV RNA expression.

"As demonstrated in our study, alcohol not only induced HCV replicon expression but also compromised anti-HCV effect of interferon alfa," Dr. Ho told Reuters Health. "These findings provide practical guidance toward the reduction of risk factors that interfere with interferon-based therapy and promote HCV disease progression."

"Our data showing that naltrexone blocks the enhancing effect of alcohol on HCV suggest that there might be an additional benefit for treating HCV-infected alcohol abusers with naltrexone," Dr. Ho added.

"One, however, has to understand that our data were generated from in vitro experiments," Dr. Ho concluded, "and clinical significance of our findings needs to be confirmed by epidemiological investigations, which is what we would like to do in the future."

Hepatology 2003;38:57-65.