Impact of Obeticholic Acid Therapy on Insulin Resistance and Metabolic Parameters in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common metabolic liver condition primarily managed through lifestyle modification. Obeticholic acid (OCA), a farnesoid X receptor agonist, has shown therapeutic benefits in steatohepatitis, yet its short-term metabolic effects remain unclear. This study compared OCA plus lifestyle modification versus lifestyle intervention alone in adults with MASLD. METHODS: This quasi-experimental study included 360 adults aged 18-60 years with ultrasound-diagnosed MASLD and insulin resistance (HOMA - IR > 2.0). Patients with diabetes mellitus, viral hepatitis, cirrhosis, advanced fibrosis, ischemic heart disease or LDL - C > 160 mg/dL were excluded. Participants received either OCA (10 mg/day) plus standardised lifestyle modification or lifestyle intervention alone for 3 months. Anthropometric, biochemical and hepatic parameters were evaluated at baseline and follow-up, with ANCOVA performed to adjust for baseline covariates. RESULTS: Baseline demographic and metabolic characteristics were comparable between groups. After 3 months, the OCA plus lifestyle group demonstrated significantly greater improvements in ALT (36.65 ± 20.57 vs. 48.19 ± 21.35 U/L; p < 0.001), fatty liver index (55.99 ± 12.60 vs. 63.08 ± 11.89; p < 0.001) and HEPAMET score (0.33 ± 0.13 vs. 0.41 ± 0.13; p < 0.001), along with a greater reduction in body weight (77.28 ± 12.07 kg vs. 80.19 ± 12.37 kg; p = 0.024). Postintervention HOMA-IR was significantly lower with OCA plus lifestyle than lifestyle alone (2.46 ± 0.92 vs. 2.96 ± 1.06; mean difference 0.50; p < 0.001). LDL-C increased significantly in the OCA group (139.50 ± 15.74 mg/dL vs. 131.96 ± 16.36 mg/dL; p < 0.001). CONCLUSION: Over 3 months, OCA combined with lifestyle modification improved liver enzymes, steatosis and fibrosis-related surrogate indices, and modestly reduced insulin resistance. Careful lipid monitoring is recommended, and longer term studies are required to clarify the overall metabolic and cardiovascular implications.