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.

Figure 1

Prevalence of hepatitis C virus infection in alcoholics with liver disease (LD). The bar graph represents the range of values found in each category based on studies cited in the text. HCC, hepatocellular carcinoma.

Figure 2

Histologic appearance of alcohol-induced liver disease and hepatitis C virus infection. Note the severe lobular disarray, cell dropout, steatosis, fibrosis, and lymphocytic infiltration of the portal areas.

Figure 3

Diagram illustrating the effect of alcohol on generation of anti hepatitis C virus (HCV) immune responses following genetic immunization and the central role of dendritic cells (DCs) in this process Genetic immunization is a technique that generates strong cellular immune responses to viral peptides The gene of interest is cloned into a plasmid followed by direct injection into muscle or fibroblastic cells The gene is transcribed and translated, and the protein processed where it may then be picked-up by adjacent DCs by phagocytosis. The viral protein is further processed and expressed on the cell surface with costimulatory proteins in the context of major histocompatibility complex (MHC) class I and class II molecules to activate CD8+ cytotoxic T lymphocyte (CTL) responses as well as CD4+ proliferative activity. The helper T cell (Th0) lymphocytes can mature via Th1 cytokine exposure promoting cellular immune responses or by Th2 cytokines generating B-cell antibody responses. Alcohol has its principal effect on blocking DC activity by poorly understood mechanisms and, therefore, affects both arms of the immune system in response to HCV immunization. DNA, deoxyribonucleic acid, TNF, tumor necrosis factor; IL, interleukin; IFN, interferon; mRNA, messenger ribonucleic acid.