Metabolic dysfunction and alcohol-related liver disease (MetALD): Position statement by an expert panel on alcohol-related liver disease

Abstract

In this position statement, we explore the intricate relationship between alcohol intake and metabolic dysfunction in the context of the 2023 nomenclature update for steatotic liver disease (SLD). Recent and lifetime alcohol use should be accurately assessed in all patients with SLD to facilitate classification of alcohol use in grams of alcohol per week. Alcohol biomarkers (i.e., phosphatidylethanol), use of validated questionnaires (i.e. AUDIT-C [alcohol use disorders identification test consumption]), and collateral information from friends and relatives could help facilitate differentiation between alcohol-related liver disease (ALD) per se and liver disease with both metabolic and alcohol-related components (MetALD). Heavy alcohol use can contribute to cardiometabolic risk factors such as high blood pressure, hypertriglyceridaemia, and hyperglycaemia. As a result, caution should be exercised in the application of only one metabolic dysfunction criterion to diagnose MASLD, as suggested in the 2023 nomenclature document, particularly in individuals exceeding weekly alcohol use thresholds of 140 g for women and 210 g for men. This is particularly important in those individuals with isolated high blood pressure, hypertriglyceridaemia, or hyperglycaemia, where the disease process may be driven by alcohol itself. Additionally, metabolic dysfunction and alcohol use should be reassessed over time, especially after periods of change in risk factor exposure. This approach could ensure a more accurate prognosis and effective management of SLD, addressing both metabolic and alcohol-related factors.

Keywords: MASH; MASLD; MetALD; NASH; alcohol-related liver disease; alcoholic cirrhosis; alcoholic liver disease; non-alcoholic fatty liver disease; public health.

Fig. 1.. Attributable risk of the leading drivers of steatotic liver disease, including alcohol use, increased adiposity and obesity, diabetes, dyslipidaemia, and arterial hypertension.

In particular, the attributable risk of alcohol use, from a public health perspective, refers to the proportion of disease (MASLD and MetALD) that can be directly attributed to alcohol consumption. Presence and interaction of risk factors speed up progression of liver fibrosis over time. Of note, alcohol use will have specific features that could help in identifying the leading driver of disease. MetALD, metabolic dysfunction- and alcohol-related steatotic liver disease; MASLD, metabolic dysfunction-associated steatotic liver disease.

Fig. 2.. Association between alcohol and metabolic syndrome (pathophysiological mechanisms).

ALD, alcohol-related liver disease; MetALD, metabolic dysfunction- and alcohol-related steatotic liver disease; MASLD, metabolic dysfunction-associated steatotic liver disease.

Fig. 3.. Careful assessment of alcohol use and metabolic dysfunction in individuals with suspected steatotic liver disease.

ALD, alcohol-related liver disease; AUD, alcohol use disorder; AUDIT-C, alcohol use disorders identification test consumption; HDL, high-density lipoprotein; MetALD, metabolic dysfunction- and alcohol-related steatotic liver disease; MASLD, metabolic dysfunction-associated steatotic liver disease; NIAAA, National Institute on Alcohol Abuse and Alcoholism; SLD, steatotic liver disease; T2DM, type 2 diabetes mellitus; WC, waist circumference.