Molecular mechanisms involved in the interaction effects of alcohol and hepatitis C virus in liver cirrhosis

Valeria Mas, Ryan Fassnacht, Kellie J. Archer, Daniel Maluf

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)287-297
Number of pages11
JournalMolecular Medicine
Volume16
Issue number7-8
DOIs
StatePublished - Jan 1 2010

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Hepacivirus
Liver Cirrhosis
Alcohols
Fibrosis
Genes
Alcoholic Liver Cirrhosis
Cytochrome P-450 Enzyme System
Liver Diseases
Linear Models
Cell Proliferation
Apoptosis
Viruses
Gene Expression Profiling
Chronic Hepatitis C
Alcohol Drinking
Cell Death
Down-Regulation

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Molecular mechanisms involved in the interaction effects of alcohol and hepatitis C virus in liver cirrhosis. / Mas, Valeria; Fassnacht, Ryan; Archer, Kellie J.; Maluf, Daniel.

In: Molecular Medicine, Vol. 16, No. 7-8, 01.01.2010, p. 287-297.

Research output: Contribution to journalArticle

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