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The intersection between alcohol-related liver disease and nonalcoholic fatty liver disease

Nature Reviews Gastroenterology & Hepatology volume 20, pages 764–783 (2023)Cite this article

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Abstract

Nonalcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ALD) are the leading causes of chronic liver disease worldwide. NAFLD and ALD share pathophysiological, histological and genetic features and both alcohol and metabolic dysfunction coexist as aetiological factors in many patients with hepatic steatosis. A diagnosis of NAFLD requires the exclusion of significant alcohol consumption and other causes of liver disease. However, data suggest that significant alcohol consumption is often under-reported in patients classified as having NAFLD and that alcohol and metabolic factors interact to exacerbate the progression of liver disease. In this Review, we analyse existing data on the interaction between alcohol consumption and metabolic syndrome as well as the overlapping features and differences in the pathogenesis of ALD and NAFLD. We also discuss the clinical implications of the coexistence of alcohol consumption, of any degree, in patients with evidence of metabolic derangement as well as the use of alcohol biomarkers to detect alcohol intake. Finally, we summarize the evolving nomenclature of fatty liver disease and describe a recent proposal to classify patients at the intersection of NAFLD and ALD. We propose that, regardless of the presumed aetiology, patients with fatty liver disease should be evaluated for both metabolic syndrome and alcohol consumption to enable better prognostication and a personalized medicine approach.

Key points

  • Nonalcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ALD) are the leading causes of chronic liver disease globally; in many patients, both metabolic dysfunction and alcohol consumption coexist as aetiological factors of hepatic steatosis.

  • The thresholds commonly used to diagnose NAFLD aim to exclude the role of alcohol in disease progression, but current evidence indicates that even low levels can exacerbate liver injury in susceptible individuals with metabolic syndrome; at present, there are no available data to recommend a safe level of alcohol consumption in patients with NAFLD.

  • Genetic background interacts with environmental factors, such as dietary patterns, sedentarism and alcohol intake, to induce more advanced liver disease by activating multiple inflammatory and fibrogenic signals.

  • Limitations of the current nomenclature and insights into the interaction of metabolic factors and alcohol consumption have led to a global debate regarding the nomenclature of NAFLD. A recent multisociety proposal of a new nomenclature for fatty liver disease addresses the issue of overlapping NAFLD–ALD and proposes a new category, termed MetALD, to designate those patients with NAFLD (named metabolic dysfunction-associated steatotic liver disease (MASLD) in the new nomenclature) who consume alcohol beyond 140–350 g per week and 210–420 g per week for women and men, respectively.

  • Identifying under-reported alcohol consumption in patients with presumed NAFLD using alcohol biomarkers is highly desirable.

  • Further research should include conducting new prospective studies to better characterize the clinical course of patients with metabolic dysfunction and varying degrees of alcohol consumption, developing new biomarkers for disease diagnosis and monitoring, and evaluating the efficacy of therapies developed for NAFLD in patients with dual-aetiology NAFLD and ALD.

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Fig. 1: Pathophysiological mechanisms involved in development and progression of NAFLD and ALD.
Fig. 2: Key pathogenic mechanisms in dual-aetiology nonalcoholic/alcohol-related fatty liver disease.
Fig. 3: Fatty liver disease spectrum and clinical considerations for management.

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Acknowledgements

The authors were partially supported by the Chilean government through the Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT projects 1200227 to J.P.A. and 1191145 to M.A.). R.B. is supported by grants from the National Institutes of Alcohol and Alcoholism (NIAAA U01AA021908 and U01AA020821).

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Authors and Affiliations

  1. Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile

    Luis Antonio Díaz, Juan Pablo Arab & Marco Arrese

  2. Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University & London Health Sciences Centre, London, Ontario, Canada

    Juan Pablo Arab

  3. Department of Epidemiology and Biostatistics, Schulich School of Medicine, Western University, London, Ontario, Canada

    Juan Pablo Arab

  4. Service des Maladies de l’Appareil Digestif, Hôpital Huriez, Lille Cedex, France

    Alexandre Louvet

  5. Université Lille Nord de France, Lille, France

    Alexandre Louvet

  6. Unité INSERM INFINITE 1286, Lille, France

    Alexandre Louvet

  7. Liver Unit, Hospital Clinic, Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

    Ramón Bataller

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  1. Luis Antonio Díaz
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The authors contributed equally to all aspects of the article.

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Correspondence to Marco Arrese.

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Díaz, L.A., Arab, J.P., Louvet, A. et al. The intersection between alcohol-related liver disease and nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol 20, 764–783 (2023). https://doi.org/10.1038/s41575-023-00822-y

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