International journal of hepatology · 2026
Impact of Obeticholic Acid Therapy on Insulin Resistance and Metabolic Parameters in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).
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Almansouri Majid, Shalabi Hani, Karami Mohammed, Alharthy Omar, Kabli Ali, Khalil Mohammad, Alkhattabi Maan, Mirdad Dahlia, Alharthy Ahmed, Abduljabbar Ahmed, Wazzan Mohammed, Alabsi Hatim, Maidin Siti S, Waseem Humaira, Hassan Amber
Аннотация
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.
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.