Metabolic dysfunction-associated fatty liver disease and excessive alcohol consumption are both independent risk factors for mortality.

BACKGROUND AND AIMS: MAFLD often cooccurs with excessive alcohol consumption, while its prognostic value in this group remains unclear. We aimed to study the mortality risk of MAFLD in relation to excessive alcohol consumption and its potential interactions. APPROACH AND RESULTS: We analyzed persons 25-74 years old enrolled in the National Health and Nutrition Examination Survey III cohort with available steatosis and alcohol data. Participants with viral hepatitis, body mass index < 18.5, and missing data on age or follow-up were excluded, leaving 12,656 participants for analysis with a median follow-up of 22.9 [20.9-24.8] years. MAFLD was defined as steatosis on ultrasound in the presence of metabolic dysfunction. Daily alcohol intake of ≥10 g in females and ≥20 g in males was considered excessive alcohol consumption. We quantified mortality risk with multivariate Cox regression for MAFLD and excessive alcohol consumption. Models were adjusted for age, age squared, sex, race, marital status, education, and smoking. MAFLD was present in 31% and excessive alcohol consumption in 13% and were both independently and simultaneously associated with increased mortality risk in fully adjusted models (adjusted HR [aHR], 1.21; 95% CI, 1.13-1.30 and aHR, 1.14; 95% CI, 1.04-1.26, respectively). Similarly, MAFLD was associated with increased mortality risk in participants with and without excessive alcohol consumption. Participants with both MAFLD and excessive alcohol consumption (4.0%) expressed the highest mortality risk (aHR, 1.47; 95% CI, 1.28-1.71). Results were consistent using the initial 10 years of follow-up, a stringent definition of excessive alcohol, and propensity score weighting. CONCLUSIONS: MAFLD increases mortality risk independent of excessive alcohol consumption. This underscores the importance of MAFLD, even in patients with excessive alcohol consumption.