Alcohol and hepatitis C virus-interactions in immune dysfunctions and liver damage

G. Szabó, Jack R. Wands, Ahmet Eken, Natalia A. Osna, Steven A. Weinman, Keigo MacHida, H. Joe Wang

Research output: Contribution to journalReview article

56 Citations (Scopus)

Abstract

Hepatitis C virus infection affects 170 million people worldwide, and the majority of individuals exposed to HCV develop chronic hepatitis leading to progressive liver damage, cirrhosis, and hepatocellular cancer. The natural history of HCV infection is influenced by genetic and environmental factors of which chronic alcohol use is an independent risk factor for cirrhosis in HCV-infected individuals. Both the hepatitis C virus and alcohol damage the liver and result in immune alterations contributing to both decreased viral clearance and liver injury. This review will capture the major components of the interactions between alcohol and HCV infection to provide better understanding for the molecular basis of the dangerous combination of alcohol use and HCV infection. Common targets of HCV and alcohol involve innate immune recognition and dendritic cells, the critical cell type in antigen presentation and antiviral immunity. In addition, both alcohol and HCV affect intracellular processes critical for hepatocyte and immune cell functions including mitochondrial and proteasomal activation. Finally, both chronic alcohol use and hepatitis C virus infection increase the risk of hepatocellular cancer. The common molecular mechanisms underlying the pathological interactions between alcohol and HCV include the modulation of cytokine production, lipopolysaccharide (LPS)-TLR4 signaling, and reactive oxygen species (ROS) production. LPS-induced chronic inflammation is not only a major cause of progressive liver injury and fibrosis, but it can also contribute to modification of the tissue environment and stem cells to promote hepatocellular cancer development. Alteration of these processes by alcohol and HCV produces an environment of impaired antiviral immune response, greater hepatocellular injury, and activation of cell proliferation and dedifferentiation.

Original languageEnglish
Pages (from-to)1675-1686
Number of pages12
JournalAlcoholism: Clinical and Experimental Research
Volume34
Issue number10
DOIs
Publication statusPublished - Oct 2010

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Viruses
Hepacivirus
Liver
Liver Diseases
Alcohols
Liver Neoplasms
Virus Diseases
Liver Cirrhosis
Antiviral Agents
Lipopolysaccharides
Wounds and Injuries
Infection
Chemical activation
Cell Dedifferentiation
Antigen Presentation
Cell proliferation
Chronic Hepatitis
Stem cells
Natural History
Dendritic Cells

Keywords

  • Antigen-Presenting Cells
  • CD4 T Cells
  • CD8 T Cells
  • CYP2E1
  • Cytokines
  • Cytotoxic T Lymphocytes (CTL)
  • Dendritic Cells (DCs)
  • HCV
  • HCV Core Protein
  • Hepatocellular Carcinoma (HCC)
  • Hepatocytes
  • Innate and Adaptive Immunity
  • Lieber-DeCarli diet
  • Lipopolysaccharide (LPS)
  • Mitochondrial Ca
  • Mitochondrial Dysfunction
  • Mn-Superoxide Dismutase (SOD2)
  • NS5a Protein
  • Proteasome
  • Reactive Oxygen Species (ROS)
  • Toll-Like Receptor 4 (TLR4)
  • Transgenic Mice

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Psychiatry and Mental health
  • Toxicology

Cite this

Alcohol and hepatitis C virus-interactions in immune dysfunctions and liver damage. / Szabó, G.; Wands, Jack R.; Eken, Ahmet; Osna, Natalia A.; Weinman, Steven A.; MacHida, Keigo; Joe Wang, H.

In: Alcoholism: Clinical and Experimental Research, Vol. 34, No. 10, 10.2010, p. 1675-1686.

Research output: Contribution to journalReview article

Szabó, G. ; Wands, Jack R. ; Eken, Ahmet ; Osna, Natalia A. ; Weinman, Steven A. ; MacHida, Keigo ; Joe Wang, H. / Alcohol and hepatitis C virus-interactions in immune dysfunctions and liver damage. In: Alcoholism: Clinical and Experimental Research. 2010 ; Vol. 34, No. 10. pp. 1675-1686.
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