Positive association between serum uric acid and metabolic dysfunction-associated steatotic liver disease: insights from a Japanese health checkup cohort.

BACKGROUND

In 2023, non-alcoholic fatty liver disease (NAFLD) was defined as metabolic dysfunction-associated steatotic liver disease (MASLD) to avoid stigmatizing terminology. Although recent studies have suggested an association between MASLD and serum uric acid (SUA), the evidence remains limited. In this study, we aimed to assess the association between MASLD and SUA in Japanese participants.

METHODS

This cross-sectional study included 3,264 eligible participants (1,917 men and 1,347 women) who underwent voluntary health checkups at Juntendo University Hospital, Tokyo, Japan, between January 2021 and December 2023. Data on basic characteristics, anthropometric indices, blood pressure, glycemic and lipid markers, SUA levels, and medical histories were collected. Steatosis was assessed by computed tomography or ultrasound. MASLD was defined as imaging-confirmed steatosis plus at least one metabolic dysfunction criterion. The participants were stratified into sex-specific SUA quartiles. Associations between MASLD and SUA quartiles were evaluated by multivariable logistic and Poisson regression, adjusted for age, alcohol consumption, smoking, estimated glomerular filtration rate, urate-lowering medication use, and body mass index. The results are reported as adjusted odds ratios (AORs) or prevalence ratios (PRs) with 95% confidence intervals (CIs).

RESULTS

Higher SUA levels were significantly associated with MASLD prevalence. After adjustment for confounders, the association remained significant. Compared with the lowest quartile, the AORs (95% CI) for MASLD in men were: Q2, 1.45 (1.08–1.97, p < 0.01); Q3, 1.43 (1.04–1.95, p < 0.01); and Q4, 2.00 (1.45–2.76, p < 0.01). In women, the AORs were: Q2, 1.45 (0.90–2.35, p = 0.13); Q3, 2.21 (1.39–3.53, p < 0.01); and Q4, 3.52 (2.22–5.56, p < 0.01). SUA that was treated as a continuous variable showed a clear dose–response association in both sexes. Sensitivity analyses using imaging-defined steatosis yielded consistent results.

CONCLUSIONS

SUA levels were positively associated with MASLD in both men and women, with women showing elevated MASLD risk even at SUA levels below the conventional hyperuricemia threshold. SUA might serve as a clinically relevant metabolic indicator; consideration of sex-specific metabolic risk might improve MASLD risk assessment. Further research on clarifying causal pathways is warranted. CLINICAL TRIAL NUMBER: Not applicable.