Linking Hyperuricemia to Disease Progression in Non-Alcoholic Fatty Liver Disease: Evidence from a Multi-Center Cohort

Abstract

Non-alcoholic fatty liver disease (NAFLD) has emerged as the most common chronic liver condition worldwide, with progression to non-alcoholic steatohepatitis (NASH), fibrosis, and cirrhosis leading to substantial morbidity. Emerging evidence suggests that hyperuricemia may play a contributory role in the progression of NAFLD, but robust multi-center cohort data are limited.This study aimed to investigate the association between hyperuricemia and disease progression in NAFLD patients using data from a large, multi-center cohort.A total of 1,250 patients with NAFLD were enrolled from five tertiary care centers and followed for a median of 5 years. Serum uric acid levels were measured at baseline. Disease progression was defined as worsening fibrosis stage, development of NASH, or progression to cirrhosis, assessed through liver biopsies, imaging, and non-invasive biomarkers. Multivariate Cox proportional hazards models were used to identify independent predictors of progression.Hyperuricemia was present in 37.6% of the cohort. Patients with hyperuricemia had significantly higher rates of disease progression compared to those with normal uric acid levels (34.8% vs. 19.5%, p<0.001). After adjusting for confounders including age, sex, body mass index, diabetes, and baseline fibrosis, hyperuricemia remained an independent predictor of NAFLD progression (adjusted HR: 1.87; 95% CI: 1.45–2.41; p<0.001). Kaplan-Meier analysis demonstrated that hyperuricemic patients had a significantly faster time to progression.Hyperuricemia is a strong and independent predictor of disease progression in patients with NAFLD. Monitoring serum uric acid levels could enhance risk stratification, and future interventional studies targeting uric acid metabolism may open new avenues for preventing NAFLD-related liver damage.