Associations between serum uric acid related ratios and the onset of metabolic dysfunction associated steatotic liver disease

Abstract

To investigate the relationship between SUA-related ratios [the SUA-to-creatinine ratio (UCR) and the SUA-to-high-density lipoprotein cholesterol ratio (UHR)] and the risk of new-onset metabolic dysfunction-associated steatotic liver disease (MASLD) prospectively. In this study, data from 37,575 patients from the Dalian Health Management Cohort (DHMC) were analysed. A restricted cubic spline was used to analyse the nonlinear relationship between the SUA-related ratios and MASLD. Generalized additive mixed models were used to evaluate the interaction of SUA with SCr and HDL-C levels. Cox proportional risk modelling was used to explore the relationships between SUA-related ratios and MASLD scores. Results were validated through subgroup and sensitivity analyses. Receiver operating characteristic curves and decision curve analysis evaluated predictive utility. During follow-up (mean 3.20 years), 891 (2.37%) developed lean MASLD and 7,043 (18.74%) nonlean MASLD. Higher UCR and UHR were associated with greater cumulative risk (log-rank test P = 0.001). Each 1.0-SD increase in UCR and UHR conferred 23% (HR: 1.23, 95%CI: 1.21-1.26) and 28% (HR: 1.28, 95%CI: 1.24-1.33) greater MASLD risk, respectively. Nonlinear relationships were observed (P_nonlinearity<0.001). The results of the ROC curves indicate C statistics of 0.773 and 0.769, respectively, with the incorporation of UCR and UHR into the base model. Elevated UCR and UHR independently predict MASLD incidence, demonstrating utility for risk stratification in both lean and nonlean populations.

Keywords: Generalized additive model; Metabolic dysfunction-associated steatotic liver disease; The serum uric acid to creatinine ratio; The serum uric acid to high-density lipoprotein cholesterol ratio.

Fig. 1

Flowchart of the study participants. MASLD: metabolic dysfunction-associated steatotic liver disease; SUA: serum uric acid; SCr: serum creatinine.

Fig. 2

Association of the UCR and UHR with the risk of MASLD. Restricted cubic spline analyses with 5 knots for nonlinear associations between SUA-related ratios and MASLD on a continuous scale. HRs are indicated by solid lines, and 95% CIs are indicated by dotted lines. The UCR and UHR distributions are indicated by shaded areas. Adjusted for age, sex, WC, BMI, SBP, DBP, FPG, TC, HDL-C, ALT, AST, γ-GGT, BUN, and eGFR. UCR: Serum uric acid to creatinine ratio; UHR: Serum uric acid to high-density lipoprotein cholesterol ratio.

Fig. 3

Effect of the Combined Interaction of SUA with SCr and HDL-C on MASLD. A shows the effect of the interaction of SUA with SCr on total MASLD; B shows the effect of the interaction of SUA with HDL-C on total MASLD; covariance exclusion was performed for curve fitting, adjusting for age, sex, WC, BMI, SBP, DBP, FPG, TC, HDL-C, ALT, AST, γ-GGT, BUN, and eGFR. LDL-C: high-density lipoprotein cholesterol; SUA: serum uric acid; SCr: serum creatinine.

Fig. 4

Effects of the UCR and UHR on new-onset MASLD in different subgroups. Each subgroup was adjusted for confounders other than the grouping variables of age, sex, WC, BMI, SBP, DBP, FPG, TC, HDL-C, ALT, AST, γ-GGT, BUN, and eGFR. UCR: serum uric acid to creatinine ratio; UHR: serum uric acid to high-density lipoprotein cholesterol ratio; T2DM: type II diabetes mellitus.

Fig. 5

The decision curve analysis of the UCR and UHR on new-onset MASLD. The vertical axis represents the standardized net benefit, while the two horizontal axes denote the risk threshold and the cost-benefit ratio, respectively. The solid gray line indicates the intervene for all strategy, and the solid black line represents the intervene for none strategy. The model was adjusted for the following covariates: age, sex, WC, BMI, SBP, DBP, FPG, TC, HDL-C, ALT, AST, γ-GGT, BUN, and eGFR.