Abstract
BACKGROUND: Gout, an inflammatory arthritis characterized by monosodium urate crystal deposition, affects 1-4% of the global population and demonstrates strong associations with metabolic syndrome. Metabolic dysfunction-associated fatty liver disease (MASLD), affecting 38% of adults worldwide, represents a multisystem disorder with substantial morbidity and mortality. This first European prospective cohort study systematically examines the association between MASLD and incident gout risk. METHOD: Utilizing UK Biobank data (n = 402,083 after exclusions), we conducted a prospective cohort analysis excluding participants with baseline gout, arthritis, hepatitis B/C, alcohol-related liver disease, or events within the initial 2-year follow-up. Cox proportional hazards models evaluated MASLD-gout associations, with Kaplan-Meier curves illustrating cumulative incidence. RESULT: MASLD patients exhibited a 71% elevated gout risk versus non-MASLD counterparts (HR = 1.71, 95% CI 1.59-1.83, P < 0.0001). Subgroup analyses revealed consistent associations across demographics, with attenuated risk in older adults (≥ 65 years: HR = 1.55 vs. < 65 years: HR = 1.86). Paradoxically, individuals without diabetes, hypertension, or central obesity demonstrated a higher gout risk than those with these comorbidities. MASLD patients showed significantly greater cumulative gout incidence over time (P < 0.001). CONCLUSION: MASLD independently associates with increased gout risk, persisting after comprehensive confounder adjustment. These findings underscore MASLD's potential role in gout pathogenesis and highlight the clinical relevance of targeted MASLD interventions for gout prevention. Mechanistic and causal investigations remain warranted.