Divergent risk profiles for cause-specific mortality in MASLD and MetALD: a nationwide population-based study

Metabolic-dysfunction-associated steatotic liver disease (MASLD) and MASLD with increased alcohol intake (MetALD) are overlapping but distinct conditions that influence liver disease progression and mortality. This study sought to examine how differing metabolic, behavioral, and sociodemographic profiles influence mortality in MASLD and MetALD.

Adults aged 20-79 years without a history of cancer, cardiovascular disease, or viral hepatitis were selected from the Korean National Health and Nutrition Examination Surveys (2007-2015). Mortality data up to November 2023 were obtained from the National Death Registry. MASLD and MetALD were defined using the hepatic steatosis index, cardiometabolic risk factors (CMRFs), and alcohol consumption.

A total of 7,783 participants, weighted to represent approximately 7.6 million Korean adults, were included, with a median follow-up duration of approximately 4 years. Both MASLD and MetALD were associated with increased all-cause mortality compared to controls, with a significant increase observed in MetALD (HR 2.085; 95% CI, 1.127-3.860; p = 0.019). The absolute all-cause mortality rates were 2.33% in the MetALD group and 1.05% in controls. Cancer-related mortality was significantly elevated in both MASLD (HR 2.610; 95% CI, 1.029-6.618; p = 0.043) and MetALD (HR 3.355; 95% CI, 1.097-10.263; p = 0.034). In MetALD, high alcohol consumption and current smoking were independent predictors of cancer-related and all-cause mortality. In MASLD, female sex and higher income were associated with reduced mortality. Cardiovascular mortality did not differ significantly between groups; however, in MASLD, each additional CMRF was associated with increased cardiovascular mortality (HR 1.838; 95% CI, 1.320-2.558; p < 0.001).

While both MASLD and MetALD were associated with increased mortality, the contributing risk profiles differed. Alcohol-related behaviors predominated in MetALD, whereas metabolic and sociodemographic factors influenced outcomes in MASLD.