BACKGROUND AND AIMS: Currently, there is no pharmacotherapy for non-alcoholic steatohepatitis (NASH), a common liver disorder. In contrast, primary biliary cholangitis (PBC) is a chronic cholestatic liver disease for which ursodeoxycholic acid (UDCA) is the drug of choice. However, 50% of PBC patients may not respond to UDCA. Obeticholic acid (OCA) is emerging as a vital pharmacotherapy for these chronic disorders. We aimed to analyse the safety and efficacy of OCA. METHODS: We performed an extensive search of electronic databases from 01/01/2000 to 31/03/2020. We included randomized controlled trials of OCA in patients with NASH, PBC, and primary sclerosing cholangitis (PSC). We assessed the histological improvement in NASH, reduction in alkaline phosphatase (≤1.67 ULN) in PBC, and the adverse effects of OCA. RESULTS: Seven RCTs (n = 2834) were included. Of the total RCTs, there were three on both NASH and PBC and one on PSC. OCA improved NASH fibrosis [OR: 1.95 (1.47-2.59; p < 0.001)]. With the 10 mg OCA dose, the odds of improvement was 1.61 (1.03-2.51; p = 0.03), while with the 25 mg dose, it was 2.23 (1.55-3.18; p < 0.001). However, 25 mg OCA led to significant adverse events and discontinuation of the drug [2.8 (1.42-3.02); p < 0.001)] compared with 10 mg OCA [0.95 (0.6-1.5); p = 0.84] in NASH patients. In PBC patients, the response to 5 mg OCA was better than with the higher doses [5 mg: 7.66 (3.12-18.81; p < 0.001), 10 mg: 5.18 (2-13.41; p = 0.001), 25 mg: 2.36 (0.94-5.93; p = 0.06), 50 mg: 4.08 (1.05-15.78; p = 0.04)]. The risk of pruritus was lowest with 5 mg OCA. CONCLUSIONS: Lower doses of OCA are effective and safe in NASH and cholestatic liver disease. While 10 mg OCA is effective for NASH fibrosis regression, only 5 mg OCA is required for PBC.
BACKGROUND AND AIMS: Currently, there is no pharmacotherapy for non-alcoholic steatohepatitis (NASH), a common liver disorder. In contrast, primary biliary cholangitis (PBC) is a chronic cholestatic liver disease for which ursodeoxycholic acid (UDCA) is the drug of choice. However, 50% of PBC patients may not respond to UDCA. Obeticholic acid (OCA) is emerging as a vital pharmacotherapy for these chronic disorders. We aimed to analyse the safety and efficacy of OCA. METHODS: We performed an extensive search of electronic databases from 01/01/2000 to 31/03/2020. We included randomized controlled trials of OCA in patients with NASH, PBC, and primary sclerosing cholangitis (PSC). We assessed the histological improvement in NASH, reduction in alkaline phosphatase (≤1.67 ULN) in PBC, and the adverse effects of OCA. RESULTS: Seven RCTs (n = 2834) were included. Of the total RCTs, there were three on both NASH and PBC and one on PSC. OCA improved NASH fibrosis [OR: 1.95 (1.47-2.59; p < 0.001)]. With the 10 mg OCA dose, the odds of improvement was 1.61 (1.03-2.51; p = 0.03), while with the 25 mg dose, it was 2.23 (1.55-3.18; p < 0.001). However, 25 mg OCA led to significant adverse events and discontinuation of the drug [2.8 (1.42-3.02); p < 0.001)] compared with 10 mg OCA [0.95 (0.6-1.5); p = 0.84] in NASH patients. In PBC patients, the response to 5 mg OCA was better than with the higher doses [5 mg: 7.66 (3.12-18.81; p < 0.001), 10 mg: 5.18 (2-13.41; p = 0.001), 25 mg: 2.36 (0.94-5.93; p = 0.06), 50 mg: 4.08 (1.05-15.78; p = 0.04)]. The risk of pruritus was lowest with 5 mg OCA. CONCLUSIONS: Lower doses of OCA are effective and safe in NASH and cholestatic liver disease. While 10 mg OCA is effective for NASH fibrosis regression, only 5 mg OCA is required for PBC.