ORIGINAL RESEARCH article
Front. Med.
Sec. Hepatobiliary Diseases
Volume 12 - 2025 | doi: 10.3389/fmed.2025.1686975
Non-linear Association of the Uric Acid to High-density Lipoprotein Cholesterol Ratio with non-alcoholic fatty liver disease and Diabetes Effect Modification in Chinese Adults: A Secondary Analysis
Provisionally accepted
- Jieyang People's Hospital, Jieyang, China
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Background: Global non-alcoholic fatty liver disease (NAFLD) prevalence has risen sharply, highlighting an urgent need for improved non-invasive biomarkers. The uric acid to high-density lipoprotein cholesterol ratio (UHR) integrates key metabolic pathways in NAFLD, but its precise relationship and effect modifiers remain unclear. Herein, we explored the correlation between UHR and NAFLD. Methods: This secondary analysis used data from 1,592 Chinese adults (40-70 years) undergoing health checks. NAFLD was diagnosed via ultrasound. UHR was calculated as serum uric acid (μmol/L) divided by high-density lipoprotein cholesterol ratio (HDL-C) (mmol/L). Association between UHR and NAFLD was assessed using multivariable logistic regression, restricted cubic splines (RCS) for non-linearity, and threshold analysis. Receiver Operating Characteristic analysis was utilized to assess the ability of UHR to predict the NAFLD. Subgroup analyses explored effect modification. Results: NAFLD prevalence was 61.1%. After full adjustment, each one standard deviation (SD) increase in UHR was associated with 22% higher NAFLD odds (odds ratio [OR] = 1.22, 95% confidence interval [CI]: 1.03-1.46). RCS revealed significant non-linearity (P<0.001). A threshold was identified at UHR Z-score = -0.75: below this, each 1-SD increase conferred a 4.6-fold higher NAFLD risk (OR=4.64, 95%CI:1.57-13.68); above it, no association was found. Diabetes significantly modified the association (P-interaction=0.028): UHR predicted NAFLD in non-diabetics (OR=1.27, 95%CI:1.04-1.56) but not diabetics. UHR's predictive ability (area under the curve = 0.670) exceeded that of uric acid or HDL-C alone. Conclusions: UHR is an independent, non-linear predictor of NAFLD in Chinese adults, with a distinct risk threshold. Its association with NAFLD is significantly modified by diabetes status. UHR represents a simple, readily available biomarker potentially enhancing NAFLD risk assessment, particularly in non-diabetic individuals.
Keywords: Non-alcoholic fatty liver disease, Uric Acid, High-density lipoprotein cholesterol, ratio, non-linear
Received: 16 Aug 2025; Accepted: 22 Sep 2025.
Copyright: © 2025 Wu, Chen, Huang and Shi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xietong Shi, 13923557308@163.com
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