Hepatitis C Virus and Alcohol

Abstract

This review will focus on the prevalence of hepatitis c virus (HCV) infection in alcoholics with and without liver disease. Evidence will be presented to demonstrate that ethanol and chronic HCV infection synergistically accelerate liver injury. Some of the major postulated mechanisms responsible for disease progression include high rates of apoptosis, lipid peroxidation, and generation of free radicals and reactive oxygen species with reduced antioxidant capacity of the liver. Acquisition and persistence of HCV infection may be due to the adverse effects of ethanol on humoral and cellular immune responses to HCV. Dendritic cells (DC) appear to be one of the major targets for ethanol's action and DC dysfunction impairs the ability of the host to generate viral specific cluster of differentiation 4 (CD4+) and cluster of differentiation 8 (CD8+) immune responses. There is a relationship between increased alcohol intake and decreased response to interferon (IFN) therapy, which may be reversed by abstinence. Clinical studies are needed to optimize treatment responses in alcoholic patients with chronic HCV infection. KeywordsHepatic C virus; cellular immune response; liver disease Chronic hepatitis C virus (HCV) infection is a major cause of liver disease, cirrhosis, and hepatocellular carcinoma (HCC) in alcoholics. 1 Since chronic ethanol abuse in the setting of persistent HCV infection accelerates the progression of liver disease, we will focus on several pathogenic mechanisms of how acute and chronic liver injury is produced by both alcohol and HCV infection. The critical role of the host cellular immune response will be addressed including clinical and pre-clinical studies that document alcohol suppressive effects on generation of viral specific cluster of differentiation 4 (CD4+) and cluster of differentiation 8 (CD8+) immune responses required for HCV elimination from the liver. It appears that dendritic cells (DCs) are a critical cellular target of alcohol, and acute and chronic exposure substantially inhibits the ability of these cells to function as antigen-presenting cells. Because alcohol has effects on interferon-(IFN-) generated signal transduction pathways that modulate immune responses, patients suffering from alcoholism may have suboptimal therapeutic responses to antiviral agents. Reduced efficacy of treatment may also be related to HCV RNA titers, extent of liver fibrosis, increased hepatic fat deposition, and decreased cellular immunity. EPIDEMIOLOGYStudies on the prevalence of HCV were made possible in 1989 by discovery of the virus and subsequent generation of anti-HCV markers. 2 The first generation enzyme-linked Address for correspondence and reprint requests: Jack R. Wands, M.D., Director, Division of Gastroenterology and The Liver Research Center, Warren Alpert Medical School of Brown University, 55 Claverick Street, 4th Floor, Providence, RI 02903 (jack_wands_md@brown.edu). NIH Public Access Author ManuscriptSemin Liver Dis. Author manuscript; available in PMC 2010 June 28. NIH-PA A...

New Insights Into the Relationships Among Alcohol Consumption, Hepatocellular Carcinoma and Hepatitis C Virus Infection

“…This result was reported in a study by Takahashi et al The mean polymerase chain reaction polymorphism, related to hyper-variable regions, was higher in patients consuming alcohol, compared to the ones who abstain (45,46). 9) Alcohol impairs cell-mediated immunity by the inhibition of DCs, which results in hindering the immune system to overcome HCV infection (44). In addition, it has been reported that under the effects of alcohol, interleukin 2 (IL-2) and IL-12 production is reduced and IL-10 production is increased (36,47,48).…”

“…Consequently, interferon IFN therapy for chronic hepatitis C is less effective in heavy drinkers than in non-drinkers (13). Researches have indicated that anti-HCV response rates were inversely proportional to alcohol consumption (44). Moreover, a six month period of abstinence may not be sufficient to resolve this negative effect on treatment outcomes (86).…”

Prediction of Sustained Virological Response to Combination Therapy with Pegylated Interferon Alfa and Ribavirin in Patients with Genotype 3 Chronic Hepatitis C

“…In our study, patients without cirrhosis achieved higher SVR as compared to cirrhotics (Table 2); however, this was not statistically significant and might be due to a smaller number of cirrhotic patients in this study. Although it has been established that chronic alcoholics have a high incidence of HCV infection, the reasons for these high rates are unknown, but may partially relate to the effects of alcohol on the humoral and cellular immune responses to viral structural and nonstructural proteins [4,37,38]. Despite the frequent presence of HCV infection in subjects with chronic alcoholism, the impact of alcohol use on treatment outcomes with antiviral agents is poorly understood.…”

“…Habitual drinking suppresses the innate immunological response to HCV infection. In turn, mutation in the HCV genome could easily occur, resulting in an increased viral diversity and increased resistance to IFN therapy [38].…”

Alcoholic Cirrhosis and Hepatocellular Carcinoma

“…Chronic alcohol consumption is an established risk modifi er of HCC development in patients with other, non-alcoholic concomitant liver diseases, particularly viral hepatitis [ 28 ], hereditary hemochromatosis (HH) [ 29 ] and non-alcoholic fatty liver disease (NAFLD) [ 30 ]. Hepatitis B and C infections account for the large majority of HCC cases in the developing world, whereas NAFLD along with the obesity epidemic is an increasing cause of HCC in Western countries.…”