Consumption of Alcohol in the Presence of Hepatitis C Virus Is an Additive Risk for Liver Damage

Ohta, Setsuko; Watanabe, Yohko; Nakajima, Tamie

doi:10.1006/pmed.1998.0298

Cited by 8 publications

(1 citation statement)

References 24 publications

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“…Epidemiological studies have established that alcohol consumption and viral hepatitis infection act synergistically to promote the development and progression of liver disease (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11). For example, excess alcohol consumption predisposes individuals to viral hepatitis B (HBV) and C (HCV) infection (1)(2)(3)(4), and viral hepatitis infection with alcohol consumption is associated with the accelerated progression of liver injury (2,6), higher frequency of cirrhosis (7)(8)(9), and higher incidence of hepatocellular carcinoma (HCC) (10,11). However, the mechanism underlying the interaction of alcohol and hepatitis virus is unknown.…”

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confidence: 99%

Additive activation of hepatic NF‐κB by ethanol and hepatitis B protein X (HBX) or HCV core protein: involvement of TNF‐α receptor 1‐independent and ‐dependent mechanisms

et al. 2001

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Alcohol consumption and viral hepatitis infection synergistically accelerate liver injury, but the underlying mechanism is not fully understood. Here we have examined the effects of ethanol on hepatitis B protein X (HBX)- or hepatitis C core protein (HCV core protein)-mediated activation of NF-kappaB, a critical signal in hepatic injury, regeneration, and tumor transformation. Acute ethanol or acetaldehyde exposure potentiates HBX or HCV core protein activation of NF-kappaB in primary mouse hepatocytes. Such potentiation can be abolished by blocking ethanol metabolism or overexpression of dominant negative NF-kappaB-inducing kinase (NIK), IkappaB kinase (IKK), or IkappaB. Moreover, pertussis toxin attenuates NF-kappaB activation induced by acetaldehyde but not by HBX or HCV core protein, whereas HBX or HCV core protein-mediated activation of NF-kappaB is abolished completely in tumor necrosis factor a receptor 1 (TNFR1) (-/-) hepatocytes. Finally, chronic ethanol consumption induces hepatic CYP2E1 protein expression and potentiates HBX or HCV core protein activation of NF-kappaB in the liver. These findings suggest that ethanol activates hepatic NF-kappaB via its metabolism and that HBX or HCV core protein activates hepatic NF-kappaB via TNFR1. With the essential role of TNFR1 in alcoholic liver injury, targeting TNFR1 by hepatitis viral proteins could contribute to cooperative effects of alcohol consumption and viral hepatitis on liver disease.

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