Serum Uric Acid and Metabolic Dysfunction–Associated Steatotic Liver Disease: A Two-Stage NHANES Study of MASLD Prevalence and All-Cause Mortality

Background: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a growing public health challenge, highlighting the need for accessible markers of metabolic liver disease risk. Serum uric acid (SUA) has been linked to metabolic dysfunction, but its association with MASLD across the full clinical spectrum, including conventionally normal SUA ranges, and its prognostic relevance remain incompletely characterized. We evaluated the association between SUA and MASLD, including the dose–response relationship, and examined whether baseline SUA was associated with all-cause mortality among adults with MASLD. Methods: We performed a two-stage study using National Health and Nutrition Examination Survey data from 1999 to 2020. Stage 1 assessed the cross-sectional association between SUA and MASLD prevalence among 28,199 adults using survey-weighted logistic regression with quadratic and restricted cubic spline modeling. MASLD was defined according to 2023 multi-society consensus criteria as hepatic steatosis plus at least one metabolic abnormality. Stage 2 prospectively followed 6623 adults with MASLD for all-cause mortality using survey-weighted Cox proportional hazards models. Results: SUA demonstrated a significant nonlinear association with MASLD prevalence. In the primary adjusted model, each 1 mg/dL increase above the population-weighted mean SUA of 5.38 mg/dL was associated with 26% higher odds of MASLD (OR: 1.26, 95% CI: 1.22–1.31), with attenuation at higher concentrations. The highest estimated odds occurred around 8.5 mg/dL (OR: 1.40, 95% CI: 1.23–1.59). Among adults with MASLD, higher baseline SUA was associated with increased all-cause mortality (HR: 1.11 per 1 mg/dL, 95% CI: 1.01–1.23), with evidence of nonlinearity at higher concentrations (quadratic HR: 1.03, p < 0.001; C-index 0.84). Conclusion: In this nationally representative two-stage study, SUA was independently associated with MASLD prevalence and all-cause mortality among adults with MASLD. SUA may represent an accessible adjunctive marker of metabolic risk and prognosis in MASLD, although further longitudinal and mechanistic studies are needed to clarify causality and clinical utility. Prospectively Registered Protocol: https://osf.io/khe3u .