Efficacy and safety of ursodeoxycholic acid in children with cholestasis: A systematic review and meta-analysis

OBJECTIVES: Ursodeoxycholic acid (UDCA) is the main therapeutic drug for cholestasis, but its use in children is controversial. We conducted this study to evaluate the efficacy and safety of ursodeoxycholic acid in children with cholestasis. METHODS: We searched Medline (Ovid), Embase (Ovid), Cochrane Central Register of Controlled Trials (CENTRAL), CNKI, WanFang Data and VIP from the establishment of databases to July 2022. Eligible studies included Chinese or English randomized controlled trials (RCTs) comparing the efficacy and safety of no UDCA (placebo or blank control) and UDCA in children with cholestasis. This study had been registered with PROSPERO (CRD42022354052). RESULTS: A total of 32 RCTs proved eligible, which included 2153 patients. The results of meta-analysis showed that UDCA could improve symptoms of children with cholestasis (risk ratio 1.24, 95% CI 1.18 to 1.29; moderate quality of evidence), and serum levels of alanine aminotransferase, total bilirubin, direct bilirubin and total bile acid (low quality of evidence). For some children with specific cholestasis, UDCA could also effectively drop serum levels of aspartate aminotransferase (parenteral nutrition-associated cholestasis) and γ-glutamyl transferase (infantile hepatitis syndrome, parenteral nutrition-associated cholestasis). The most common adverse drug reactions (ADRs) of UDCA in children were gastrointestinal adverse reactions, with an incidence of 10.63% (67/630). There was no significant difference in the incidence of ADRs between UDCA and placebo/blank control groups (risk difference 0.03, 95%CI -0.01 to 0.06; moderate quality of evidence), and among children taking different UDCA doses (P = 0.27). CONCLUSION: The available short-term evidence showed that UDCA was effective and safe for children with cholestasis. Clinicians should use UDCA with caution (start with a low dose) until the long-term effect is further explored in future larger RCTs.