Association of High-Density Lipoprotein Cholesterol-Based Inflammatory Markers with MASLD and Significant Liver Fibrosis in US Adults: Insights from NHANES 2017–2020

Background: Systemic inflammation and lipid metabolism disturbances are important hallmarks of the onset and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to explore the association of lymphocyte-high-density lipoprotein-cholesterol ratio (LHR), monocyte-HDL-C ratio (MHR), neutrophil-HDL-C ratio (NHR), and platelet-HDL-C ratio (PHR) with MASLD and significant liver fibrosis using NHANES 2017-2020 data. Methods: LHR, MHR, NHR, and PHR were calculated based on complete blood count parameters and serum HDL-C. MASLD and liver fibrosis were diagnosed based on transient elastography. Multivariate logistic regression analyses were used to explore these associations, and receiver operating characteristic (ROC) was used to compare the predictive power of these markers. Results: A total of 8,341participants were included, and the prevalence of MASLD and significant liver fibrosis was 45.1% and 11.57%, respectively. In fully adjusted models, log-transformed LHR, MHR, NHR, and PHR were positively associated with the odds of MASLD (odds ratio [OR] 1.853, 1.685, 1.470, and 1.879, respectively) and significant liver fibrosis (OR 1.570, 1.425, 1.396, and 1.384, respectively) (all p < 0.05). Most of these associations were nonlinear and significant positive correlations existed only after their respective inflection points. The association of LHR with significant liver fibrosis was more pronounced in men. ROC analysis showed that LHR/NHR was superior in predicting MASLD, whereas MHR/NHR distinguished significant liver fibrosis better than other markers. Conclusions: LHR, MHR, NHR, and PHR were independently associated with MASLD and liver fibrosis in US adults and may serve as emerging predictors. Future cohort studies are needed to confirm these findings and explore clinical predictive value.