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Advances in Alcoholic Liver Disease

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Abstract

Alcoholic liver disease (ALD) remains a leading cause of death from liver disease in the United States. In studies from the Veterans Administration, patients with cirrhosis and superimposed alcoholic hepatitis had greater than 60% mortality over a 4-year period, with most of those deaths occurring in the first month. Thus, the prognosis for this disease is more ominous than for many common types of cancer (eg, breast, prostate, and colon). Moreover, ALD imposes a significant economic burden from lost wages, health care costs, and lost productivity. Unfortunately, there is still no Food and Drug Administration–approved or widely accepted drug therapy for any stage of ALD. Thus, a pressing need exists for a more detailed understanding of mechanisms of liver injury. This article reviews recent advances in mechanisms and therapy related to five major areas of direct relevance to ALD: oxidative stress; gut-liver axis and cytokine signaling; malnutrition; fibrin/clotting; and stellate cell activation/fibrosis. We also review why therapies related to these mechanisms have performed well in experimental animals and in vitro systems, but have not necessarily translated into effective therapy for humans with ALD.

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Acknowledgments

This work was supported by National Institutes of Health grants R01AA003624 (Arteel), R01AA015970 (McClain), R37AA010762 (McClain), R01DK071765 (McClain), P01AA017103 (McClain), R01AA018016 (McClain), RC2AA019385 (McClain), R01AA018869 (McClain), and the Veterans Administration (McClain).

Disclosure

Conflicts of interest: J. Beier—none; G. Arteel—none; C. McClain—fees and honoraria from Vertex, Ocera, Gilead, Baxter, and Nestle, grants or contracts with Roche, Merck, Axcan, and Gilead.

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, University of Louisville Health Sciences Center, Louisville, KY, 40292, USA

    Juliane I. Beier, Gavin E. Arteel & Craig J. McClain

  2. University of Louisville Alcohol Research Center, University of Louisville Health Sciences Center, Louisville, KY, 40292, USA

    Juliane I. Beier, Gavin E. Arteel & Craig J. McClain

  3. Department of Medicine, University of Louisville Health Sciences Center, Clinical and Translational Research Building, Room 503, 505 South Hancock Street, Louisville, KY, 40292, USA

    Craig J. McClain

  4. Robley Rex Veterans Administration Medical Center, Louisville, KY, 40206, USA

    Craig J. McClain

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  1. Juliane I. Beier
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  2. Gavin E. Arteel
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Correspondence to Craig J. McClain.

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Beier, J.I., Arteel, G.E. & McClain, C.J. Advances in Alcoholic Liver Disease. Curr Gastroenterol Rep 13, 56–64 (2011). https://doi.org/10.1007/s11894-010-0157-5

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