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. 2025 Apr 17;25(1):268.
doi: 10.1186/s12876-025-03805-2.

MAFLD mediates the association between CHR and gallstones in the U.S. adults: evidence from NHANES 2021-2023

Xin Feng  1 , Xiangyu Song  1 , Xi'an Yang  1 , Fuxiang Luan  1 , Yufei Gu  2 , Fengyu Zheng  3 , Huahu Guo  1 , Shishi Qiao  4
Affiliations

MAFLD mediates the association between CHR and gallstones in the U.S. adults: evidence from NHANES 2021-2023

Xin Feng et al. BMC Gastroenterol. .

Abstract

Background: Gallstones, a global hepatobiliary disorder, are linked to systemic inflammation, lipid disturbances, and metabolic-associated fatty liver disease (MAFLD). This population-based study aims to investigate the association of the novel inflammation-lipid composite biomarker high-sensitivity C-reactive protein-to-HDL cholesterol ratio (CHR) with gallstones and evaluate whether MAFLD mediates this relationship.

Methods: This cross-sectional analysis utilized data from the National Health and Nutrition Examination Survey (NHANES, 2021-2023) to assess the correlation between the CHR and gallstone prevalence through weighted logistic regression. To evaluate potential nonlinear relationships and assess heterogeneity across key demographics, restricted cubic splines (RCS) were employed to model the association, complemented by subgroup analyses stratified by age, sex, and other covariates. A mediation analysis was used for elucidating the mediating effects of MAFLD.

Results: Among 4,078 participants, 432 (10.60%) had gallstones. After adjusting for confounders, each unit increase in CHR was associated with a 165% increased risk of gallstones (OR: 2.65, 95% CI: 1.43-4.93, P = 0.006). The RCS curve demonstrated a nonlinear association between the CHR and gallstones (Poverall < 0.001, Pnonlinear < 0.001). Mediation analysis indicated that MAFLD explained 27.1% of this association.

Conclusions: CHR is positively associated with gallstones, with MAFLD partially mediating this relationship. Managing CHR levels and preventing MAFLD may reduce gallstone incidence.

Keywords: Cross-sectional studies; Gallstones; High-density lipoprotein cholesterol; High-sensitivity C-reactive protein; Metabolic associated fatty liver disease; NAHNES.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The NCHS Ethics Review Board granted ethical clearance to conduct this study. All participants provided informed consent before inclusion. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
2021–2023 NHANES Study Population Flowchart
Fig. 2
Fig. 2
RCS analysis of the CHR and gallstones
Fig. 3
Fig. 3
Subgroup analyses of the association between the CHR and risk of gallstones
Fig. 4
Fig. 4
Mediating effect of MAFLD on the association between the CHR and gallstone prevalence
See this image and copyright information in PMC

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