Molecular Mechanisms Involved in the Interaction Effects of Alcohol and Hepatitis C Virus in Liver Cirrhosis

Abstract

The mechanisms by which alcohol consumption accelerates liver disease in patients with chronic hepatitis C virus (HCV) are not well understood. To identify the characteristics of molecular pathways affected by alcohol in HCV patients, we fit probe-set level linear models that included the additive effects as well as the interaction between alcohol and HCV. The study included liver tissue samples from 78 patients, 23 (29.5%) with HCV-cirrhosis, 13 (16.7%) with alcohol-cirrhosis, 23 (29.5%) with HCV/alcohol cirrhosis and 19 (24.4%) with no liver disease (no HCV/no alcohol group). We performed gene-expression profiling by using microarrays. Probe-set expression summaries were calculated by using the robust multiarray average. Probe-set level linear models were fit where probe-set expression was modeled by HCV status, alcohol status, and the interaction between HCV and alcohol. We found that 2172 probe sets (1895 genes) were differentially expressed between HCV cirrhosis versus alcoholic cirrhosis groups. Genes involved in the virus response and the immune response were the more important upregulated genes in HCV cirrhosis. Genes involved in apoptosis regulation were also overexpressed in HCV cirrhosis. Genes of the cytochrome P450 superfamily of enzymes were upregulated in alcoholic cirrhosis, and 1230 probe sets (1051 genes) had a significant interaction estimate. Cell death and cellular growth and proliferation were affected by the interaction between HCV and alcohol. Immune response and response to the virus genes were downregulated in HCV-alcohol interaction (interaction term alcohol*HCV). Alcohol*HCV in the cirrhotic tissues resulted in a strong negative regulation of the apoptosis pattern with concomitant positive regulation of cellular division and proliferation.

General and Cancer Mortality in a Large Cohort of Italian Alcoholics

“…This estimate could be due to the local prevalence of hepatitis C virus (HCV) (Bardazzi et al, 2000); it is well known that alcohol may interact with HCV infection in the development of liver cirrhosis (Mas et al, 2010). Unfortunately, the lack of individual data on HCV infection in our series cannot allow us to evaluate this association.…”

Acute and chronic viral hepatitis

“…Alcoholics with alcohol-related liver disease are at significantly increased risk for developing chronic HCV infection, while those without alcoholrelated liver disease are not. 292 The precise mechanisms for these effects are not known, but are hypothesized to include: enhancement of immune-mediated antiviral damage to alcohol-altered hepatocyte membranes; alcohol inhibition of liver regeneration; enhancement by alcohol of viral replication; and concomitant immune suppression. These findings suggest that HCV infection enhances the injury induced by alcohol or, conversely, that alcoholic liver disease increases the risk of HCV infection or progression of HCV infection to chronicity.…”

“…In fact, several studies report an increase in the frequency of HCV markers as the histological severity of alcoholic liver disease increases. 288,289,292 As noted above, mild to moderate steatosis is often identified in association with hepatitis C and, by itself, neither suggests nor excludes the possibility of concomitant alcoholic liver disease. [288][289][290] From the diagnostic point of view, if biopsy specimens taken for documentation of alcoholic liver disease contain features more typical of chronic hepatitis, a significant proportion will be hepatitis C positive.…”

An Overview and Evaluation of Combining an Addiction Liaison Nurse Outpatient Service With Hepatitis C Outpatient Clinics in Glasgow, Scotland

“…In patients with HCV, alcohol consumption expedites the progression of liver fibrosis (and for some, cirrhosis) (Mahl & O'Grady, 2006 ) and has a negative impact on outcomes (Mas, Fassnacht, Archer, & Maluf, 2002 ). Mas et al (2002) imply that the impact alcohol has with HCV may be due to it reducing the effectiveness of the body's immune system. Alcohol is highlighted as the biggest barrier to HCV treatment because it is said to reduce the effectiveness of antiviral therapy (Dieperink et al, 2010 ).…”