Mortality Risk in Steatotic Liver Disease Stratified by Cardiometabolic Risk Factors and Alcohol Consumption: A Nationwide Cohort Study

Background/Aims: Steatotic liver disease (SLD) has emerged as a new nomenclature; however, the long-term outcomes of SLD associated with its subtypes have been understudied. We aimed to investigate the all-cause and cause-specific mortality risk across SLD subtypes. Methods: Health checkup results of 2,049,641 Korean individuals were analyzed. SLD was defined as a Fatty Liver Index ≥30. Mortality risks in metabolic dysfunction-associated SLD (MASLD), metabolic dysfunction and alcohol-related liver disease (MetALD), and alcohol-associated liver disease (ALD) were investigated considering cardiometabolic risk factors (CMRFs) and alcohol consumption. Multivariable Cox proportional hazards models were used to calculate the adjusted hazard ratios (HRs). Results: Compared with no SLD, MASLD (HR, 1.28; 95% confidence interval [CI], 1.24 to 1.30), MetALD (HR, 1.40; 95% CI, 1.36 to 1.44), and ALD (HR, 1.70; 95% CI, 1.65 to 1.75) showed higher risks of all-cause mortality. All subtypes had an increased cause-specific mortality risk from liver-related disease, extrahepatic cancer, and cardiovascular disease, with liver-related mortality being the most prominent (HR, 2.57; 95% CI, 2.36 to 2.80 for MASLD; HR, 4.34; 95% CI, 3.93 to 4.78 for MetALD; HR, 6.23; 95% CI, 5.65 to 6.91 for ALD). The cumulative incidence of all-cause mortality increased as the number of CMRFs increased in all subtypes. The number of CMRFs affecting the mortality risk was the most pronounced in MASLD but the least pronounced in ALD. Conclusions: This study demonstrated that MASLD, MetALD, and ALD had an increased risk of all-cause and cause-specific mortality compared with no SLD. The impact of the number of CMRFs on mortality risk was most pronounced in MASLD, calling for more customized management strategies.