Fibrate-Statin Combination Therapy and Change of Hepatic Steatosis-Related Indices in Patients with Dyslipidemia: A Retrospective Study Using Korean National Health Insurance Data

BACKGROUND: The role of fibrates in modifying hepatic steatosis-related outcomes remains uncertain, particularly in real-world populations receiving statin therapy for dyslipidemia. We investigated the association between fibrate use and longitudinal changes in hepatic steatosis-related indices in statin-treated patients with moderate hypertriglyceridemia using nationwide health screening data. METHODS: We analyzed data from 307,992 adults with triglyceride level of 150-500 mg/dL receiving statin therapy, identified from the Korean National Health Insurance Service database. Participants were classified according to fibrate exposure (users vs. non-users). Hepatic steatosis was operationally assessed using two validated surrogate indices, the fatty liver index (FLI) and the hepatic steatosis index (HSI), measured at baseline and follow-up health checkups. Propensity score matching was performed to balance baseline characteristics. Subgroup analyses were conducted according to medication possession ratio (MPR <0.8 vs. ≥0.8). RESULTS: In propensity score-matched analyses, fibrate use was associated with lower odds of hepatic steatosis as defined by FLI (odds ratio [OR], 0.89; 95% confidence interval [CI], 0.84 to 0.95) and HSI (OR, 0.82; 95% CI, 0.78 to 0.87). Among participants with high medication adherence (MPR ≥0.8), stronger associations were observed (FLI OR, 0.30; HSI OR, 0.34). CONCLUSION: In this large nationwide cohort, fibrate use in statin-treated patients with moderate hypertriglyceridemia was associated with lower prevalence of hepatic steatosis-related indices, particularly among individuals with high medication adherence. These findings should be interpreted as associations based on surrogate markers rather than definitive evidence of histologic improvement. Further studies incorporating imaging or histological endpoints are warranted to clarify the role of fibrates in the management of metabolic dysfunction-associated steatotic liver disease.