The association between the hs-CRP/HDL-C ratio and nonalcoholic fatty liver disease: The mediating role of insulin resistance in a cross-sectional study using NHANES 2017–2020

The hs-CRP/HDL-C ratio, an emerging marker of lipid metabolism abnormalities and inflammation, has not been thoroughly studied in relation to nonalcoholic fatty liver disease (NAFLD). This study aimed to evaluate its association with NAFLD and examine the mediating role of insulin resistance (IR). Using NHANES data from 2017 to 2020, 3127 adult participants were included. The hs-CRP/HDL-C ratio was divided into 4 quartiles. Multivariable logistic regression, restricted cubic spline (RCS) analysis, and mediation analysis were employed to evaluate the relationship between the ratio and NAFLD risk, and the mediating effect of IR. Subgroup analyses assessed the ratio's predictive role across different populations. All analyses were weighted to ensure representativeness. The hs-CRP/HDL-C ratio was positively correlated with the risk of NAFLD, with the hs-CRP/HDL-C ratio in NAFLD patients significantly higher than that in the non-NAFLD group (P < .001). As the hs-CRP/HDL-C ratio increased, the prevalence of NAFLD significantly increased (19.11% vs 41.38% vs 52.33% vs 60.27%, P < .001). In the multivariable logistic regression model, the unadjusted Model 1 showed that for each unit increase in the hs-CRP/HDL-C ratio, the risk of NAFLD increased by 23% (P < .05). The RCS analysis showed that the hs-CRP/HDL-C ratio had a nonlinear relationship with the risk of NAFLD, with inflection points at approximately 0.34, 0.58, and 0.60, indicating a significant increase in risk near these points. Subgroup analysis found that marital status had a significant interaction effect in the relationship between the risk of NAFLD and hs-CRP/HDL-C ratio (P < .05). Mediation analysis showed that HOMA-IR played a significant mediating role in the relationship between the hs-CRP/HDL-C ratio and the risk of NAFLD (mediating effect accounted for 40.8% of the total effect, P = .008). This study revealed a positive correlation between the hs-CRP/HDL-C ratio and the risk of NAFLD, and insulin resistance played an important mediating role in this relationship. This ratio has potential predictive value in the early screening and prevention of NAFLD.