Inflammation–metabolism composite (CRP–triglyceride–glucose index) predicts all-cause and cardiovascular mortality in MASLD with advanced fibrosis: Evidence from a national NHANES cohort

Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent and associated with metabolic dysfunction, systemic inflammation, and increased cardiovascular risk. The C-reactive protein-Triglyceride-Glucose Index (CTI) is a novel composite biomarker reflecting low-grade inflammation and insulin resistance. However, its prognostic value for long-term mortality in patients with MASLD and advanced fibrosis remains unclear. Therefore, this study aimed to investigate the association between CTI and the risk of all-cause and cardiovascular mortality in individuals with MASLD using a nationally representative cohort. We used data from National Health and Nutrition Examination Survey 2001 to 2018 and included 8791 adults with MASLD. Advanced fibrosis was defined by FIB-4, NAFLD Fibrosis Score, and AST-to-Platelet Ratio Index. Survey-weighted Cox models evaluated associations between CTI (per standard deviation increase) and all-cause and cardiovascular mortality. Restricted cubic splines examined dose-response patterns. Effect modification by sex, age, and race/ethnicity was assessed in stratified analyses. Over follow-up, 1806 deaths occurred. Higher CTI was independently associated with increased all-cause (HR 1.16, 95% confidence interval [CI]: 1.12-1.20) and cardiovascular mortality (HR 1.12, 95% CI: 1.04-1.20) in MASLD. Among participants with advanced fibrosis, CTI remained associated with all-cause (HR 1.14, 95% CI: 1.07-1.23) and cardiovascular mortality (HR 1.14, 95% CI: 1.01-1.29). Splines showed a U-shaped association between CTI and mortality in MASLD (nadir CTI ~7.5-7.9) but an approximately linear positive association in advanced fibrosis. Associations were stronger in women, older adults, and racial/ethnic minorities. Our observational findings suggest that CTI is associated with long-term all-cause and cardiovascular mortality in MASLD and advanced fibrosis. As a simple, integrative biomarker, CTI may help refine early risk stratification in high-risk MASLD populations.