Original Decreased dose and shorter duration of obeticholic acid in nonalcoholic steatohepatitis patient: a randomized control trial

Background and aims: Non-alcoholic fatty liver diseases (NAFLD) have a spectrum of conditions where the progressive form is nonalcoholic steatohepatitis (NASH). However, to date, there is a lack of approved therapies for NASH. In this study, we aimed to explore the impact of smaller doses and shorter duration of obeticholic acid on NASH. Methods: In this, open-label randomized control trial, 36 adult non/diabetic patients with NAFLD activity score (NAS) >= 5 were included. Patients were assigned to obeticholic acid 10 mg twice daily with lifestyle modification (group-OCAL) and only lifestyle modification (group-L) after 1:1 randomization for 24 weeks. The primary outcome was measured with NAS improvement >= 2 without worsening of fibrosis. Results: A total of 31 NASH patients were evaluated as per standard protocol at the end of the study. Among them, 15 belonged to the OCAL group, and 16 belonged to the L group. Baseline epidemiological, metabolic, anthropometric, biochemical, and histological observations were similar in both groups. After 24 weeks NAS improved in the OCAL group from 5.53 +/- 0.60 to 3.40 +/- 1.1 (P<0.001) and in the L group from 5.31 +/- 0.50 to 4.44 +/- 1.20 (P=0.011). In the OCAL group, fibrosis improved from 1.40 +/- 0.80 to 0.67 +/- 0.60, (P=0.001). NASH >= 2 improvement without worsening fibrosis in the OCAL group was 13 (68%) and 6 (32%) in the L group. ALT, AST, and GGT were significantly improved in the OCL group. Histological improvement was irrespective of weight reduction and status of diabetes. Conclusion: Obeticholic acid of a decreased dose of 20 mg daily for a shorter duration of 24 weeks improved NASH and fibrosis, independent of weight reduction and diabetes.