Remnant cholesterol inflammatory index and MASLD in U.S. adults: mediation role of triglyceride-glucose index.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is driven by dyslipidemia and chronic inflammation. We proposed a novel biomarker, the Remnant Cholesterol Inflammatory Index (RCII), and evaluated its association with MASLD, considering mediation via insulin resistance (TyG index). Methods: In 3,232 U.S. adults from NHANES 2015-2020 (709 with MASLD), participants were divided into RCII tertiles. Multivariable logistic regression, restricted cubic splines, threshold analysis, subgroup interaction tests, ROC curves, XGBoost SHAP, and mediation analysis were used to assess relationships and mechanisms. Results: Compared with the lowest tertile, the highest RCII tertile had an OR of 9.578 (95 % CI 6.420-14.291; P < 0.001) for MASLD. A nonlinear association was identified, with a stronger slope below RCII = 3.640 (1-unit increase associated with 76.1 % higher odds). Significant interaction was observed by smoking status. In SHAP ranking, RCII was the sole lipid-class feature among the top five predictors. ROC showed AUC = 0.747 for RCII versus 0.732 for RC, both outperforming TC/LDL-C. TyG index mediated 32.4 % of RCII's total effect on MASLD (P < 0.001). Conclusions: RCII is a robust lipid-inflammation marker that outperforms conventional lipids in predicting MASLD. Its association is partly mediated by insulin resistance, supporting RCII's use in MASLD risk stratification and early prevention.