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Diagnosis and Treatment of Alcohol-Associated Liver DiseaseA Review

Educational Objective
To review the spectrum of alcohol-associated liver disease (ALD) and its diagnosis and treatment.
1 Credit CME

Importance  Alcohol-associated liver disease results in cirrhosis in approximately 10% to 20% of patients. In 2017, more than 2 million people had alcohol-associated cirrhosis in the US. Alcohol-associated liver disease is the primary cause of liver-related mortality and the leading indication for liver transplant, representing 40% to 50% of all liver transplant in high-income countries.

Observations  Steatosis, alcoholic hepatitis, and fibrosis are the 3 pathologic findings that are associated with progression to cirrhosis, with highest risk in patients with alcoholic hepatitis. The amount and duration of alcohol consumption, female sex, obesity, and specific genetic polymorphisms such as patatin-like phospholipase domain protein 3, membrane bound O-acyltransferase, and transmembrane 6 superfamily member 2 genes are risk factors for alcohol-associated liver disease progression. Ten-year survival of patients with alcohol-associated liver disease is 88% among those who are abstinent and 73% for those who relapse to alcohol consumption. Symptomatic alcoholic hepatitis is characterized by rapid onset of jaundice and a 30% risk of mortality 1 year after diagnosis. Severe alcoholic hepatitis, defined as a modified discriminant function score greater than or equal to 32 or Model for End-Stage Liver Disease score (starts at 6 and capped at 40; worst = 40) greater than 20, is associated with the development of acute-on-chronic liver failure and multiorgan failure. Corticosteroid therapy is associated with improved 1-month survival from 65% in untreated patients to 80% in treated patients. Early liver transplant may be appropriate in highly select patients with severe alcoholic hepatitis who do not respond to medical therapy. In patients with decompensated cirrhosis, liver transplant should be considered if the Model for End-Stage Liver Disease score remains greater than 17 after 3 months of alcohol abstinence. Between 2014 and 2019, the proportion of patients waiting for liver transplantation who had alcohol-associated liver disease increased from 22% to 40%. Alcohol-associated cirrhosis accounted for approximately 27% of 1.32 million deaths worldwide related to cirrhosis in 2017.

Conclusions and Relevance  Alcohol-associated liver disease is among the most common liver diseases and more than 2 million people in the US in 2017 had alcohol-associated cirrhosis. Corticosteroid therapy improves survival in select patients with severe alcoholic hepatitis. Liver transplantation is the most effective therapy in patients with decompensated liver disease.

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Article Information

Corresponding Authors: Ashwani K. Singal, MD, University of South Dakota Sanford School of Medicine, 1815 S Cliff Ave, Sioux Falls, SD 57105 (ashwanisingal.com@gmail.com); Philippe Mathurin, MD, Hospital Huriez, Rue Michel Polonowski, 59000 Lille, France (philippe.mathurin@chru-lille.fr).

Accepted for Publication: April 29, 2021.

Author Contributions: Dr Singal had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design, acquisition, analysis, or interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content, and administrative, technical, or material support: Both authors.

Conflict of Interest Disclosures: Dr Singal reported receiving personal fees from Gilead Pharmaceuticals and the American College of Gastroenterology, nonfinancial support from the American Association for the Study of Liver Diseases, and grants from the American College of Gastroenterology and National Institute on Alcohol Abuse and Alcoholism during the conduct of the study; and grants from the National Institute of Diabetes and Digestive and Kidney Diseases, personal fees from Gilead Pharmaceuticals, Recordati Pharmaceuticals, Alnylam Pharmaceuticals, Medscape Gastroenterology, the Chronic Liver Disease Foundation, and UpToDate, and nonfinancial support from the American Porphyria Foundation outside the submitted work. Dr Mathurin reported receiving personal fees from Gilead and Verlyx during the conduct of this review, and personal fees from Bayer Healthcare, AbbVie, Ipsen, Eisai, MSD, Servier, and Sanofi outside the submitted work.

Additional Information: We acknowledge the help of Eric Daleside from the Department of Medicine, University of South Dakota Sanford School of Medicine, for media expertise in developing the figures; Gnemmi Viviane from the University of Lille and Sulaiman Raed, MD, from the Avera McKennan Hospital for providing histology slides for Figure 1; and Dale Lebrec for her expertise in English language and proofreading the article for syntax and grammar.

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Mathurin  P , Lucey  MR .  Liver transplantation in patients with alcohol-related liver disease: current status and future directions.   Lancet Gastroenterol Hepatol. 2020;5(5):507-514. doi:10.1016/S2468-1253(19)30451-0PubMedGoogle ScholarCrossref
Mathurin  P , Moreno  C , Samuel  D ,  et al.  Early liver transplantation for severe alcoholic hepatitis.   N Engl J Med. 2011;365(19):1790-1800. doi:10.1056/NEJMoa1105703PubMedGoogle ScholarCrossref
Singal  AK , Bashar  H , Anand  BS , Jampana  SC , Singal  V , Kuo  YF .  Outcomes after liver transplantation for alcoholic hepatitis are similar to alcoholic cirrhosis: exploratory analysis from the UNOS database.   Hepatology. 2012;55(5):1398-1405. doi:10.1002/hep.25544PubMedGoogle ScholarCrossref
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AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

  • 1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
  • 1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
  • 1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
  • 1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
  • 1.00 credit toward the CME [and Self-Assessment requirements] of the American Board of Surgery’s Continuous Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.

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