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. 2025 Jun 16;16(8):e00873.
doi: 10.14309/ctg.0000000000000873. eCollection 2025 Aug 1.

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

Shuangzhen Jia  1 , Xiaolin Ye  1 , Yan Kong  1 , Zhaoxia Wang  2 , Jie Wu  1
Affiliations

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

Shuangzhen Jia et al. Clin Transl Gastroenterol. .

Abstract

Introduction: 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 was used to compare the predictive power of these markers.

Results: A total of 8,341 participants 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 1.853, 1.685, 1.470, and 1.879, respectively) and significant liver fibrosis (odds ratio 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. Receiver operating characteristic analysis showed that LHR/NHR was superior in predicting MASLD, whereas MHR/NHR distinguished significant liver fibrosis better than other markers.

Discussion: 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.

Keywords: HDL-C; MASLD; liver fibrosis; steatotic liver disease; systemic inflammation.

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Conflict of interest statement

Specific author contributions: J.W. conducted and designed this work. Statistical analysis and manuscript preparation was performed by S.J. and X.Y. S.J. and Z.W. contributed to the accuracy of data analysis. Data collection and table preparation was conducted by Y.K. and X.Y. All authors reviewed the manuscript.

Financial support: This work is supported by the Beijing Hospitals Authority's Ascent Plan (DFL20221003) and the Sanming Project of Medicine in Shenzhen (No. SZSM202311023)

Potential competing interests: The authors declare no conflicts of interest, whether financial or personal, that could have influenced the work presented in this paper.

Ethics statement: All protocols were approved by the National Center for Health Statistics Ethics Review Board, and participants have provided written informed consent.

Data availability: This study analyzed publicly available datasets and can be found at https://wwwn.cdc.gov/nchs/nhanes/continuousnhanes/default.aspx?Cycle=2017-2020.

Figures

Figure 1.
Figure 1.
Flowchart of study population selection, NHANES 2017–2020.
Figure 2.
Figure 2.
RCS analysis of the association of log LHR, MHR, NHR, and PHR with MASLD. (a) LHR; (b) MHR; (c) NHR; (d) PHR. LHR, lipoprotein-cholesterol ratio; MASLD, metabolic dysfunction-associated steatotic liver disease; MHR, monocyte-HDL-C ratio; NHR, neutrophil-HDL-C ratio; PHR, platelet-HDL-C ratio.
Figure 3.
Figure 3.
RCS analysis of the association of log LHR, MHR, NHR, and PHR with significant liver fibrosis. (a): LHR; (b) MHR; (c) NHR; (d) PHR. LHR, lipoprotein-cholesterol ratio; MHR, monocyte-HDL-C ratio; NHR, neutrophil-HDL-C ratio; PHR, platelet-HDL-C ratio.
Figure 4.
Figure 4.
Stratified analysis of the association of LHR, MHR, NHR, and PHR with MASLD and significant liver fibrosis according to sex. (a) MASLD; (b) significant liver fibrosis. LHR, lipoprotein-cholesterol ratio; MASLD, metabolic dysfunction-associated steatotic liver disease; MHR, monocyte-HDL-C ratio; NHR, neutrophil-HDL-C ratio; PHR, platelet-HDL-C ratio.
Figure 5.
Figure 5.
ROC curves of LHR, MHR, NHR, and PHR for the prediction of MASLD and significant liver fibrosis. (a) MASLD; (b) significant liver fibrosis. MASLD, metabolic dysfunction-associated steatotic liver disease; MHR, monocyte-HDL-C ratio; NHR, neutrophil-HDL-C ratio; PHR, platelet-HDL-C ratio.
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