Steatotic liver disease as a risk enhancer in the presence of metabolic syndrome

Aims & Aims Steatotic liver disease (SLD) is an overarching term to encompass metabolic-dysfunction associated steatotic liver disease (MASLD), MASLD with increased alcohol intake (MetALD), and alcohol-associated liver disease (ALD). However, the impact of metabolic syndrome (MetS) on the association between SLD and mortality risk remains uncertain. This study aims to compare all-cause and cause-specific mortality across SLD subtypes stratified by MetS.Methods and results A population-based cohort study was conducted using NHANES III data, including 9217 participants stratified by MetS status and further categorized into no SLD, MASLD, MetALD, and ALD groups. MetS was defined according to the International Diabetes Federation criteria. Over a median follow-up of 26.4 years, 3521 mortality events occurred. After adjustment, SLD with MetS was significantly associated with an increased risk of all-cause mortality compared with healthy controls (HR 1.56, 95% CI 1.38-1.75). This association persisted across all SLD subtypes (MASLD: HR 1.52, 95% CI 1.34-1.72; MetALD: HR 1.92, 95% CI 1.41-2.62; ALD: HR 2.80, 95% CI 1.56-5.05). In contrast, no significant association was found between SLD subtypes without MetS and mortality risk. When stratified by MetS presence, MASLD, MetALD and ALD were each significantly associated with increased mortality risks compared with the no SLD group in individuals with MetS, primarily driven by high cancer-related and diabetes-related mortality. However, this association was not observed in the population without MetS.Conclusion This study reveals that the significant association between SLD subtypes and mortality risk is mediated by MetS. To enhance risk stratification and improve long-term health outcomes, it is crucial to distinguish between MASLD, MetALD, and other SLD types while managing metabolic status and reducing alcohol consumption.This study examines the impact of metabolic syndrome (MetS) on the association between different subtypes of steatotic liver disease (SLD) and mortality risk.People with SLD and MetS had a higher risk of mortality, particularly from cancer and diabetes, compared with those without liver disease.In contrast, SLD without MetS was not associated with a higher risk of mortality, highlighting the crucial role of metabolic health in liver disease outcomes.These findings emphasize the importance of managing metabolic health and alcohol consumption to mitigate long-term health risks.