| 12829987 |
Zhang T, Li Y, Lai JP, Douglas SD, Metzger DS, O'Brien CP, Ho WZ: Alcohol potentiates hepatitis C virus replicon expression. Hepatology. 2003 Jul;38(1):57-65.
Alcohol consumption accelerates liver damage and diminishes the anti-hepatitis C virus (HCV) effect of interferon alfa (IFN-alpha) in patients with HCV infection. It is unknown, however, whether alcohol enhances HCV replication and promotes HCV disease progression. The availability of the HCV replicon containing hepatic cells has provided a unique opportunity to investigate the interaction between alcohol and HCV replicon expression. We determined whether alcohol enhances HCV RNA expression in the replicon containing hepatic cells. Alcohol, in a concentration-dependent fashion, significantly increased HCV replicon expression. Alcohol also compromised the anti-HCV effect of IFN-alpha. Investigation of the mechanism (s) responsible for the alcohol action on HCV replicon indicated that alcohol activated nuclear factor kappaB (NF-kappaB) promoter. Caffeic acid phenethyl ester (CAPE), a specific inhibitor of the activation of NF-kappaB, abolished alcohol-induced HCV RNA expression. In addition, naltrexone, an opiate receptor antagonist, abrogated the enhancing effect of alcohol on HCV replicon expression. In conclusion, alcohol, probably through the activation of NF-kappaB and the endogenous opioid system, enhances HCV replicon expression and compromises the anti-HCV effect of IFN-alpha. Thus, alcohol may play an important role in vivo as a cofactor in HCV disease progression and compromise IFN-alpha-based therapy against HCV infection. |
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