Abstract / Summary
Abstract Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent condition closely linked to cardiovascular diseases and type 2 diabetes. Although the triglyceride-glucose (TyG) index is widely acknowledged as an indicator of insulin resistance, its standalone prognostic value for mortality in MASLD remains limited. This study evaluated whether combining the TyG index with systemic inflammatory markers-specifically TyG-MLR, TyG-NLR, TyG-SIRI, TyG-lgPLR, and TyG-lgSII-improves prediction of all-cause, cardiovascular, and diabetes‑related mortality in MASLD patients. We examined data from 7,639 adult participants diagnosed with MASLD in the National Health and Nutrition Examination Survey (NHANES) conducted between 2003 and 2018. The mortality follow-up continued until December 31, 2019. The multivariable Cox regression, Kaplan-Meier survival curve, restricted cubic splines, and receiver operating characteristic curves were used to evaluate the correlation and predictive efficacy. Over a median follow-up of 109 months, the study documented 1226 deaths from all causes, with 408 being cardiovascular-related and 183 associated with diabetes. The associations of individual TyG-inflammatory derivatives with mortality varied by cause of death, showing outcome-specific patterns. The dose-response relationships for TyG-lgPLR and TyG-lgSII exhibited J-shaped curves when examining all-cause and diabetes-specific mortality. ROC curve analysis revealed that TyG-MLR displayed superior predictive performance for all-cause and cardiovascular mortality at 1-, 3-, and 5-year follow-ups, whereas TyG-lgSII emerged as the most accurate predictor for diabetes-related mortality. Integrating the TyG index with systemic inflammatory biomarkers substantially enhances the predictive accuracy for all-cause mortality, cardiovascular death, and diabetes-related fatalities among MASLD patients. These combined indicators serve as valuable clinical instruments for individualized risk assessment and may support timely clinical decision-making. Graphical abstract This study highlights a novel and reliable evidence supporting the clinical application of combined metabolic-inflammation biomarkers to optimize the prognostic stratification of MASLD patients.