Abstract
BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is burdened by significant all-cause and cardiovascular mortality, yet simple and effective predictive indices for long-term outcomes are currently lacking. In this study, we investigated the prognostic value of the triglyceride glucose-a body shape index (TyG-ABSI), a novel composite of insulin resistance and visceral adiposity, for mortality in MASLD. METHODS: This prospective cohort study included 7515 adults with MASLD from the National Health and Nutrition Examination Survey (NHANES, 1999-2018). MASLD was defined as a Fatty Liver Index ≥ 60 accompanied by at least one cardiometabolic risk factors. The primary outcomes were all-cause mortality (ACM) and cardiovascular mortality (CVM). Kaplan-Meier survival curves, multivariable Cox regression, restricted cubic splines (RCS), and receiver operating characteristic (ROC) analyses were employed to evaluate the predictive value of TyG-ABSI. Additionally, subgroup, sensitivity, and mediation analyses were conducted to verify robustness and explore underlying mechanisms. RESULTS: During a median follow-up of 138 months, 1368 all-cause and 376 cardiovascular deaths were recorded. TyG-ABSI demonstrated improved predictive accuracy compared to TyG, TyG-BMI, TyG-WC, and TyG-WHtR, as evidenced by higher AUC values and significant Net Reclassification Improvement（NRI). In fully adjusted models, participants in the highest TyG-ABSI quartile faced significantly elevated risks of ACM (HR 1.49, 95% CI 1.03-2.14) and CVM (HR 2.32, 95% CI 1.02-5.30) relative to the lowest quartile. RCS analysis indicated a linear dose-response relationship, and the associations remained robust across subgroup and sensitivity analyses. Mediation analysis revealed that accelerated biological aging significantly mediated mortality risks, with KDM and HD explaining 24.75% and 32.15% of ACM, and 34.89% and 46.53% of CVM, respectively. CONCLUSIONS: TyG-ABSI serves as a robust, independent predictor of mortality in patients with MASLD, outperforming traditional TyG-related metrics. The association is significantly associated with the pathway of accelerated biological aging, highlighting the utility of TyG-ABSI for enhanced risk stratification in clinical practice.