MASLD/MetALD and mortality in individuals with any cardio-metabolic risk factor: A population-based study with 26.7 years of follow-up

Background and Aims: A new term, metabolic dysfunction-associated steatotic liver disease (MASLD), has been proposed by a multi-society expert panel. However, it remains unclear whether hepatic steatosis per se in MASLD contributes to an increased risk of mortality in individuals with any cardio-metabolic risk factor (CMRF), which is also a significant risk factor for increased mortality. This study aimed to compare all-cause and cause-specific mortality between the "MASLD/MetALD" and "no steatotic liver disease (SLD)" groups in individuals with any CMRF. Approach and Results: A population-based cohort study was conducted using 10,750 participants of the Third National Health and Nutrition Examination Survey. All-cause and cause-specific (cardiovascular, cancer, diabetes, and liver) mortality risks were compared between the "MASLD," "MetALD," and "no SLD" groups using the Cox proportional hazards model with complex survey design weights, adjusted for confounders. Over 26 years, the "MASLD" group did not show significantly increased all-cause (adjusted HR 1.04[95% CI: 0.95-1.14], p = 0.413), cardiovascular (0.88 [0.75-1.04], p = 0.139), or cancer (1.06[0.84-1.33], p = 0.635) mortality risk compared to the "no SLD" group in individuals with any CMRF. The MetALD group was associated with increased all-cause (1.41 [1.05-1.89], p = 0.022), cancer (2.35 [1.33-4.16], p = 0.004), and liver (15.04 [2.96-76.35], p = 0.002) mortality risk compared with the no SLD group. This trend was more pronounced in the MetALD group with advanced fibrosis assessed by Fibrosis-4 (FIB-4). Conclusions: In individuals with CMRF, the presence of steatotic liver disease (MASLD) alone did not increase the risk of mortality, except in cases with more alcohol consumption (MetALD). Therefore controlling metabolic risk factors and reducing alcohol consumption in people with MASLD or MetALD will be crucial steps to improve long-term health outcomes.