Association of the C-reactive protein–triglyceride–glucose index with liver disease risk: findings from a nationwide Chinese cohort

Both insulin resistance and low-grade inflammation contribute to liver disease development, yet their combined predictive role remains unclear at the population level. In this prospective nationwide cohort study, we analyzed 9,302 participants aged ≥ 45 years from the China Health and Retirement Longitudinal Study who were free of liver disease at baseline. Additionally, CTI was calculated as 0.412 × ln (C-reactive protein [CRP, mg/L]) + ln((triglycerides [TG, mg/dL] × fasting plasma glucose [FPG, mg/dL])/2). Incident self-reported, physician-diagnosed liver disease was identified during follow-up interviews. Associations between CTI and liver disease were assessed using Cox regression, Kaplan–Meier survival curves, and restricted cubic splines analyses. Subgroup and mediation analyses were conducted for low-density and high-density lipoprotein cholesterol. Over 81,229 person-years of follow-up, higher CTI was independently associated with an increased risk of incident self-reported, physician-diagnosed liver disease, with risk increasing progressively across CTI quartiles. This positive association was consistent in men and women, with approximately linear dose–response relationships in both sexes and no meaningful sex differences. Mediation through low- and high-density lipoprotein cholesterol was negligible. Findings remain robust in multiple sensitivity analyses, including exclusion of participants who reported high-risk alcohol consumption. Elevated CTI is a simple, low-cost biomarker that may help identify individuals at increased risk of liver disease, particularly in settings where comprehensive liver function panels are unavailable. Rather than replacing guideline-recommended fibrosis scores, CTI may serve as a complementary early risk indicator to support population-level risk stratification and inform targeted prevention and follow-up efforts.