Non-HDL-C and non-HDL-C/HDL-C ratio as predictors of hepatic steatosis: a systematic review and meta-analysis

The association between novel atherogenic indices (NAIs) and the pathophysiology of metabolic dysfunction-associated steatotic liver disease (MASLD) has been extensively researched. Among these, non-high-density lipoprotein cholesterol (non-HDL-C) and non-HDL-C/HDL-C ratio are novel indices linked to a higher risk for metabolic syndrome - and possibly MASLD. The current review evaluates the possible utility of these NAIs as markers for MASLD.

MEDLINE, Scopus, and Web of Science were systematically searched. Screening and data extraction were performed by two independent reviewers. All observational studies reporting standardized mean differences (SMD), odds ratios (ORs) and components of receiver operating characteristic (ROC) analysis were included in evidence synthesis. Meta-analysis was performed using a random effects model.

34 studies were included in the quantitative synthesis. Non-HDL-C (SMD = 1.11, 95% CI 0.49-1.73) and non-HDL-C/HDL-C (SMD = 0.77, 95% 0.55-0.98) were significantly higher in MASLD patients. Similarly both indices were associated with increased odds for development or diagnosis of MASLD (non-HDL-C OR = 1.34, 95% CI 1.19-1.48; non-HDL-C/HDL-C OR = 1.68, 95% CI 1.30-2.04). Non-HDL-C (AUC = 0.68, 95% CI 0.65-0.72) and non-HDL-C/HDL-C demonstrated "good" utility (AUC = 0.74, 95% CI 0.70-0.77) as a diagnostic marker for MASLD.

Our findings showed a significant association between these NAIs and MASLD. Both non-HDL-C and non-HDL-C/HDL-C ratio also showed an acceptable performance as biomarkers for MASLD. The use of these NAIs as part of a complex model for prediction of MASLD may prove even more beneficial in the clinical setting.

The online version contains supplementary material available at 10.1007/s40200-025-01719-0.