Review Article | Published:

Alcoholic liver disease: mechanisms of injury and targeted treatment

Nature Reviews Gastroenterology & Hepatology volume 12, pages 231242 (2015) | Download Citation

Abstract

Alcoholic liver disease (ALD) is a complex process that includes a wide spectrum of hepatic lesions, from steatosis to cirrhosis. Cell injury, inflammation, oxidative stress, regeneration and bacterial translocation are key drivers of alcohol-induced liver injury. Alcoholic hepatitis is the most severe form of all the alcohol-induced liver lesions. Animal models of ALD mainly involve mild liver damage (that is, steatosis and moderate inflammation), whereas severe alcoholic hepatitis in humans occurs in the setting of cirrhosis and is associated with severe liver failure. For this reason, translational studies using humans and human samples are crucial for the development of new therapeutic strategies. Although multiple attempts have been made to improve patient outcome, the treatment of alcoholic hepatitis is still based on abstinence from alcohol and brief exposure to corticosteroids. However, nearly 40% of patients with the most severe forms of alcoholic hepatitis will not benefit from treatment. We suggest that future clinical trials need to focus on end points other than mortality. This Review discusses the main pathways associated with the progression of liver disease, as well as potential therapeutic strategies targeting these pathways.

Key points

  • Alcoholic liver disease (ALD) is characterized by a complex spectrum of histological lesions, ranging from steatosis to cirrhosis

  • Alcoholic hepatitis is a specific entity, which is associated with a fast progression to cirrhosis and with liver failure and a poor outcome in its most severe form

  • ALD is characterized by oxidative stress, disturbance of hepatocyte metabolism, liver inflammation, modifications in the regeneration process and translocation of bacterial products from the gut microbiota into the portal blood stream

  • Because animal models do not reproduce the complete spectrum of alcohol-induced hepatic lesions, translational research based on human samples is crucial to identify new treatment options

  • The best-documented treatment for severe alcoholic hepatitis is corticosteroids, but this treatment is not ideal and 40% of patients still die after a short period of time

  • The future evaluation of new strategies in severe alcoholic hepatitis should focus not only upon survival, but also on surrogate markers of outcome, with a specific plan of development

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  1. Service des Maladies de L'appareil Digestif et Unité INSERM 995, Hôpital Huriez, Rue Polonovski, 59037 Lille Cedex, France.

    • Alexandre Louvet
    •  & Philippe Mathurin

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Both authors contributed equally to all aspects of the manuscript.

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The authors declare no competing financial interests.

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Correspondence to Philippe Mathurin.

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https://doi.org/10.1038/nrgastro.2015.35