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Anastasia-Stefania Alexopoulos1,2, Kenneth Cusi3
1Division of Endocrinology, Metabolism and Nutrition, Department of Medicine, Duke University Medical Center, Durham, NC.
Abstract:
Metabolic dysfunction-associated steatotic liver disease (MASLD) affects the majority of individuals with diabetes and severe obesity, and is one of the most common indications for liver transplantation in the U.S. Emerging evidence underscores the synergistic and detrimental impact of alcohol and metabolic disease on liver and overall health. In 2023, the nomenclature for steatotic liver disease was revised to include a new subcategory known as MetALD (metabolic dysfunction- and alcohol-associated liver disease), which acknowledges alcohol use as a cofactor in liver injury alongside metabolic risk factors. This review offers key insights into the role of alcohol use as both a direct hepatotoxin and an indirect contributor to insulin resistance, dyslipidemia, and obesity. Notably, even light-to-moderate alcohol intake may hasten MASLD progression to cirrhosis and hepatocellular carcinoma, especially in individuals with existing metabolic disease, and can worsen cardiovascular disease risk. MetALD is associated with increased all-cause, cancer-related, and liver-related mortality in comparison with MASLD, reinforcing the importance of accurate alcohol assessment in managing diabetes and obesity. Diagnosis now requires stratifying alcohol use and integrating tools such as the Alcohol Use Disorders Identification Test (AUDIT) questionnaire and phosphatidylethanol testing. The caveats and use of these tools in clinical practice are discussed. Management strategies for MASLD focus on lifestyle changes, weight loss, and medications such as glucagon-like peptide 1 receptor agonists, with emerging evidence suggesting that these agents may also reduce alcohol consumption. However, treatment data on MetALD are limited. This review offers practical guidance for health care professionals on how to integrate alcohol use into existing, recommended MASLD care pathways.
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