Abstract

Alcoholic liver disease (ALD) is the most prevalent type of chronic liver disease worldwide. ALD can progress from alcoholic fatty liver (AFL) to alcoholic steatohepatitis (ASH), which is characterized by hepatic inflammation. Chronic ASH can eventually lead to fibrosis and cirrhosis and in some cases hepatocellular cancer (HCC). In addition, severe ASH (with or without cirrhosis) can lead to alcoholic hepatitis, which is an acute clinical presentation of ALD that is associated with liver failure and high mortality. Most individuals consuming >40 g of alcohol per day develop AFL; however, only a subset of individuals will develop more advanced disease. Genetic, epigenetic and non-genetic factors might explain the considerable interindividual variation in ALD phenotype. The pathogenesis of ALD includes hepatic steatosis, oxidative stress, acetaldehyde-mediated toxicity and cytokine and chemokine-induced inflammation. Diagnosis of ALD involves assessing patients for alcohol use disorder and signs of advanced liver disease. The degree of AFL and liver fibrosis can be determined by ultrasonography, transient elastography, MRI, measurement of serum biomarkers and liver biopsy histology. Alcohol abstinence achieved by psychosomatic intervention is the best treatment for all stages of ALD. In the case of advanced disease such as cirrhosis or HCC, liver transplantation may be required. Thus, new therapies are urgently needed.

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Change history

  • 28 August 2018

    The originally published article contained an error in figure 8 part a, in which cut off values for F3 fibrosis, cirrhosis, and screening for oesophageal varices and HCC were incorrectly presented as <8 kPa, <12.5 kPa and <20 kPa, respectively. These cut off values have been corrected in the HTML and PDF versions of the manuscript to >8 kPa for F3 fibrosis, >12.5 kPa for cirrhosis and >20 kPa for screening for oesophageal varices and HCC.

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Acknowledgements

The authors thank H. Engel for her help in managing administration, English language correction and the reference list during the writing of this article.

Reviewer information

Nature Reviews Disease Primers thanks H. Tilg, M. Neuman, A. Cederbaum, T. Morgan and R. Williams for their contribution to the peer review of this work.

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Affiliations

  1. Centre of Alcohol Research (CAR),, University of Heidelberg, Heidelberg and Department of Medicine, Salem Medical Center, Heidelberg, Germany

    • Helmut K. Seitz
    •  & Sebastian Mueller
  2. Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA, USA

    • Ramon Bataller
  3. Departmento de Gastroenterologia, CHLN, Laboratorio de Nutricão, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal

    • Helena Cortez-Pinto
  4. Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD, USA

    • Bin Gao
  5. Addiction Unit, Neuroscience Institute Hospital Clinic, IDIBAPS, Barcelona, Spain

    • Antoni Gual
  6. Institute of Pathology, Medical University of Graz, Graz, Austria

    • Carolin Lackner
  7. Service des Maladies de l’Appareil Digestif, Universite Lille 2 and INSERM U795, Lille, France

    • Philippe Mathurin
  8. Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA

    • Gyongyi Szabo
  9. University of Southern California Keck School of Medicine and Greater Los Angeles VA Healthcare System, Los Angeles, CA, USA

    • Hidekazu Tsukamoto

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Contributions

Introduction (H.K.S.); Epidemiology (H.K.S. and H.C.-P.); Mechanisms/pathophysiology (H.K.S., R.B., G.S. and H.T.); Diagnosis, screening and prevention (H.K.S., A.G., C.L. and S.M.); Management (R.B., A.G. and P.M.); Quality of life (H.C.-P.); Outlook (R.B. and B.G.); Overview of Primer (H.K.S.).

Competing interests

H.K.S. has received lecture fees from the Falk Foundation and research grants from Octapharma. R.B. has no conflicts of interest. H.C.-P. has received lecture fees and advisory board fees from Genfit, Gilead Sciences, Intercept Pharmaceuticals and Merck. She is also the Policy Councillor for the European Association for the Study of the Liver. B.G. has no conflicts of interest. A.G. has received honoraria and grants for research from D&A Pharma SAS and Lundbeck Limited. He was also principal investigator in one of the nalmefene pivotal studies, investigator in the sodium oxybate trial and Spanish coordinator of the acamprosate trial (Adisa study). He is a past president of the European Federation of Addiction Societies and vice president of the International Network on Brief Interventions for Alcohol and Drugs. C.L. has no conflicts of interest. P.M. consults for Gilead Sciences and Verlyx Pharma. S.M. has previously been an adviser for Echosens. G.S. has received US NIH grant funding from the National Institute on Alcohol Abuse and Alcoholism, is employed by the University of Massachusetts Medical School and is the Editor-in-Chief of Hepatology Communications of the American Association for the Study of Liver Disease. H.T. has received grants and donations from EA Pharma, Gilead Sciences and Otsuka Pharmaceutical.

Corresponding author

Correspondence to Helmut K. Seitz.

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https://doi.org/10.1038/s41572-018-0014-7

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