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Mechanisms of alcohol-induced hepatocellular carcinoma

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Abstract

Chronic alcohol abuse is a major risk factor for hepatocellular carcinoma (HCC), the third leading cause of cancer deaths worldwide. Alcohol can also function synergistically with other risk factors to cause HCC. Hence, alcohol consumption is a major factor affecting hepatic carcinogenesis in millions and the cause of a substantial public health burden. Chronic alcohol consumption interferes with several host anti-tumor mechanisms, thereby facilitating hepatocyte proliferation and tumorigenesis. This review summarizes the major mechanisms of alcohol-induced HCC. These include pathways of ethanol metabolism, alcohol-induced oxidative stress and hypomethylation of DNA, and interplay of alcohol with iron elevation, retinoid metabolism, the immune system, inflammatory pathways, and neoangiogenesis. The relevance of each pathway in affecting HCC transformation is a topic of intense investigation. Ongoing research will enhance our insight into the alcohol-induced occurrence of HCC and offer hope in developing better therapeutics.

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Acknowledgements

This research was supported by the Intramural Research Program of the NIH (National Institute of Allergy and Infectious Diseases, and the Clinical Research Center). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.

Conflict of interest

Sreetha Sidharthan and Shyam Kottilil have no conflicts of interest to report.

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  1. Critical Care Medicine Department, Department of Health and Human Services, Clinical Center, National Institutes of Health, Bethesda, MD, USA

    Sreetha Sidharthan

  2. Laboratory of Immunoregulation, Department of Health and Human Services, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bldg10, Rm.11N204, Bethesda, MD, 20892, USA

    Shyam Kottilil

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  1. Sreetha Sidharthan
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Correspondence to Shyam Kottilil.

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Sidharthan, S., Kottilil, S. Mechanisms of alcohol-induced hepatocellular carcinoma. Hepatol Int 8 (Suppl 2), 452–457 (2014). https://doi.org/10.1007/s12072-013-9494-4

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  • DOI: https://doi.org/10.1007/s12072-013-9494-4

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