Effect of Dotinurad on Uric Acid and Hepatorenal Parameters in Steatotic Liver Disease: A Pilot Study in Japanese Patients.

Background: Dotinurad (DOT) has demonstrated beneficial metabolic effects in preclinical models as a selective uric acid reabsorption inhibitor. However, its clinical impact on steatotic liver disease (SLD) with hyperuricemia (HU-SLD) remains unclear. Methods: This observational pilot study evaluated 33 patients with HU-SLD (Metabolic dysfunction-associated steatotic liver disease: n = 20; Metabolic dysfunction-associated alcohol-related liver disease: n = 1; Alcohol-related liver disease: n = 12) treated with DOT for at least 6 months. Laboratory parameters were assessed at baseline and at 6 months. The primary outcomes were changes in serum uric acid levels, hepatobiliary function markers, and renal function markers. Results: DOT significantly reduced serum uric acid levels from 8.4 (7.7-9.0) to 6.0 (5.9-6.8) mg/dL at 6 months (p < 0.001). Regarding hepatobiliary markers, gamma-glutamyl transferase decreased from 47 (30-78) to 43 (27-54) U/L (p = 0.042) and total bilirubin decreased from 0.6 (0.5-1.0) to 0.6 (0.4-0.7) mg/dL (p = 0.023). Significant but modest improvements in renal function were also observed, with serum creatinine decreasing from 1.1 (0.9-1.3) to 1.0 (0.9-1.1) mg/dL (p = 0.010) and estimated glomerular filtration rate increasing from 55.6 (44-67.3) to 56.6 (48.8-71.5) mL/min/1.73 m2 (p = 0.007). No significant changes were observed for aspartate aminotransferase, alanine aminotransferase, fibrosis-related markers, lipid profiles, or glycemic markers. Moreover, no treatment discontinuations or adverse events were recorded during the study period. Conclusions: DOT effectively reduced serum uric acid and modestly improved renal and hepatobiliary parameters in HU-SLD without any patient-reported complications. These real-world findings support the potential of DOT as a well-tolerated therapeutic option beyond urate lowering and warrant further investigation in larger, controlled studies.