Comparative prognostic performance of triglyceride-glucose-adiposity indices for mortality in adults with metabolic dysfunction-associated steatotic liver disease

Abstract

Composite indices integrating insulin resistance and adiposity may improve mortality risk stratification in metabolic dysfunction-associated steatotic liver disease (MASLD). We evaluated eight triglyceride-glucose (TyG)-related indices in 6,159 U.S. adults with MASLD from the 1999–2018 National Health and Nutrition Examination Survey, with mortality follow-up through December 31, 2019. Survey-weighted Cox models, restricted cubic spline analyses, incremental performance metrics, decision curve analysis, and subgroup and sensitivity analyses were applied. During a median follow-up of 107 months, 1,115 deaths occurred, including 367 cardio-cerebrovascular disease (CCVD)-related deaths. In fully adjusted models, TyG-WWI was associated with both all-cause and CCVD-related mortality after Bonferroni correction. However, incremental predictive gains were small and metric-dependent. No index performed consistently best across metrics and outcomes. All eight indices showed nonlinear associations with all-cause mortality, whereas no significant evidence of nonlinearity was detected for CCVD-related mortality. Decision curves showed broadly similar net-benefit profiles across the index-augmented models, with no clearly preferred model. Sensitivity analyses yielded generally consistent estimates. Overall, the evaluated indices provided limited incremental prognostic information beyond the clinical model.