{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T13:19:15Z","timestamp":1770815955798,"version":"3.50.1"},"reference-count":110,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2015,2,5]],"date-time":"2015-02-05T00:00:00Z","timestamp":1423094400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Hepatitis C and alcohol are the most widespread causes of liver disease worldwide. Approximately 80% of patients with a history of hepatitis C and alcohol abuse develop chronic liver injury. Alcohol consumption in hepatitis C virus (HCV)-infected patients exacerbates liver disease leading to rapid progression of fibrosis, cirrhosis and even hepatocellular carcinoma. Hepatocytes are the main sites of HCV-infection and ethanol metabolism, both of which generate oxidative stress. Oxidative stress levels affect HCV replication and innate immunity, resulting in a greater susceptibility for HCV-infection and virus spread in the alcoholic patients. In this review paper, we analyze the effects of ethanol metabolism and other factors on HCV replication. In addition, we illustrate the mechanisms of how HCV hijacks innate immunity and how ethanol exposure regulates this process. We also clarify the effects of HCV and ethanol metabolism on interferon signaling\u2014a crucial point for activation of anti-viral genes to protect cells from virus\u2014and the role that HCV- and ethanol-induced impairments play in adaptive immunity which is necessary for recognition of virally-infected hepatocytes. In conclusion, ethanol exposure potentiates the suppressive effects of HCV on innate immunity, which activates viral spread in the liver and finally, leads to impairments in adaptive immunity. The dysregulation of immune response results in impaired elimination of HCV-infected cells, viral persistence, progressive liver damage and establishment of chronic infection that worsens the outcomes of chronic hepatitis C in alcoholic patients.<\/jats:p>","DOI":"10.3390\/biom5010076","type":"journal-article","created":{"date-parts":[[2015,2,5]],"date-time":"2015-02-05T10:54:42Z","timestamp":1423133682000},"page":"76-94","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Hepatitis C, Innate Immunity and Alcohol: Friends or Foes?"],"prefix":"10.3390","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7498-0556","authenticated-orcid":false,"given":"Natalia","family":"Osna","sequence":"first","affiliation":[{"name":"Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, 4101 Woolworth Ave, Omaha, NE 68105, USA"},{"name":"Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68105, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Murali","family":"Ganesan","sequence":"additional","affiliation":[{"name":"Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, 4101 Woolworth Ave, Omaha, NE 68105, USA"},{"name":"Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68105, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7759-8889","authenticated-orcid":false,"given":"Kusum","family":"Kharbanda","sequence":"additional","affiliation":[{"name":"Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, 4101 Woolworth Ave, Omaha, NE 68105, USA"},{"name":"Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68105, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2015,2,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.drugalcdep.2010.05.008","article-title":"Alcohol impairs interferon signaling and enhances full cycle hepatitis C virus JFH-1 infection of human hepatocytes","volume":"112","author":"Ye","year":"2010","journal-title":"Drug Alcohol Depend."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/S1521-6918(03)00018-0","article-title":"Liver disease in alcohol and hepatitis C","volume":"17","author":"Jamal","year":"2003","journal-title":"Best Pract. 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