The efficacy and safety of high-dose compared with low-dose ursodeoxycholic acid for primary sclerosing cholangitis: A meta-analysis.

Background and Aim: Primary sclerosing cholangitis (PSC) is a progressive cholestatic liver disease with no proven effective medical therapy. Several randomized controlled trials have investigated the safety and efficacy of either high- or low-dose ursodeoxycholic acid (UDCA) compared with placebo as a potential treatment strategy, with conflicting results. The aim of this meta-analysis was to determine the efficacy and safety of high-dose (>15 mg/kg/day) versus low-dose (<= 15 mg/kg/day)UDCAin treating PSC. Method(s): We searched the Cochrane Library, MEDLINE, Embase, and the Web of Science for eligible studies comparing high- or low-dose UDCA in adult patients with PSC from 1990 to 2017. The primary end points evaluated were patient mortality, liver transplantation, clinical symptoms (fatigue and/or pruritus), serum biochemistry, progression of liver histology, and adverse events. The Mantel-Haenszel method was used to estimate the pooled risk ratios for binary outcomes, and Cohen's weighted mean difference for continuous outcomes. Heterogeneity was measured using the chi-squared test. Result(s): Fourteen studies (12 randomized controlled trials and two phase 3 studies) with 883 patients were included. Eight studies investigated low doses (10-15 mg/kg/day), four studies assessed high doses (17-30 mg/kg/ day), and two studies used both high- and low-doseUDCAin parallel. There were no significant differences between high- and low-dose UDCA with respect to mortality (relative risk [RR], 1.08; 95% CI, 0.35-3.29), progression of liver histology (RR, 0.27; 95% CI, 0.03-2.7), and adverse events (RR, 0.55; 95% CI, 0.09-3.38). There were no significant differences between high-dose UDCA and placebo with respect to mortality (RR, 0.98; 95% CI, 0.36-2.65), treatment failure (RR, 1.15; 95% CI, 0.96-2.24), adverse events (RR, 1.08; 95% CI, 0.96-2.24), cholangiographic deterioration (RR, 0.59; 95% CI, 0.27-1.30), clinical symptoms (fatigue and/or pruritus) (RR, 5; 95% CI, 0.26