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World J Gastroenterol. May 28, 2011; 17(20): 2507-2514
Published online May 28, 2011. doi: 10.3748/wjg.v17.i20.2507
Involvement of autophagy in alcoholic liver injury and hepatitis C pathogenesis
Natalia A Osna, Paul G Thomes, Terrence M Donohue Jr
Natalia A Osna, Paul G Thomes, Terrence M Donohue Jr, University of Nebraska Medical Center, VA Medical Center, Omaha, NE 68105, United States
Author contributions: All authors contributed equally to this manuscript; Osna NA and Donohue TM Jr reviewed the current literature; Thomes PG provided much of the preliminary data on alcohol and autophagy mentioned in the text.
Supported by NIAAA, R21AA017232 and Dean’s Reviewed Research Grant of the University of Nebraska Medical Center
Correspondence to: Natalia A Osna, MD, PhD, University of Nebraska Medical Center, VA Medical Center, 4101 Woolworth Ave, Omaha, NE 68105, United States. nosna@unmc.edu
Telephone: +1-402-9953735 Fax: +1-402-4490604
Received: January 7, 2011
Revised: March 23, 2011
Accepted: March 30, 2011
Published online: May 28, 2011
Abstract

This review describes the principal pathways of macroautophagy (i.e. autophagy), microautophagy and chaperone-mediated autophagy as they are currently known to occur in mammalian cells. Because of its crucial role as an accessory digestive organ, the liver has a particularly robust autophagic activity that is sensitive to changes in plasma and dietary components. Ethanol consumption causes major changes in hepatic protein and lipid metabolism and both are regulated by autophagy, which is significantly affected by hepatic ethanol metabolism. Ethanol exposure enhances autophagosome formation in liver cells, but suppresses lysosome function. Excessive ethanol consumption synergizes with hepatitis C virus (HCV) to exacerbate liver injury, as alcohol-consuming HCV patients frequently have a longer course of infection and more severe manifestations of chronic hepatitis than abstinent HCV patients. Alcohol-elicited exacerbation of HCV infection pathogenesis is related to modulation by ethanol metabolism of HCV replication. Additionally, as part of this mechanism, autophagic proteins have been shown to regulate viral (HCV) replication and their intracellular accumulation. Because ethanol induces autophagosome expression, enhanced levels of autophagic proteins may enhance HCV infectivity in liver cells of alcoholics and heavy drinkers.

Keywords: Autophagy; Iysosome; Autophagosome; Hepatitis C virus; Hepatitis C virus replication cycle; Ethanol