Ursodeoxycholic Acid: Efficacy and Safety in the Treatment of Nonalcoholic Fatty Liver Disease (Meta-Analysis)

Abstract

Вackground: Non-alcoholic liver disease (NAFLD) is a widely spread disease that needs an effective and safe treatment strategy. One of pharmacological treatments for people with NAFLD is ursodeoxycholic acid (UDCA). The use of UDCA is pathogenetically justified because of its cytoprotective, antiapoptotic, antioxidant, and hypoglycemic properties. Aim: Our meta-analysis (M-A) aimed to assess the benefits and harms of UDCA in people with NAFLD. Material and methods: We identified trials through electronic searches in the Cochrane Hepato-Biliary (CHB) Controlled Trials Register, CENTRAL, MEDLINE, Embase, SCI, LILACS, eLibrary (May 2018). We considered for inclusion randomised clinical trials (RCTs) assessing URSO versus placebo/no intervention in adult participants with NAFLD. We allowed co-interventions in the trial groups if they were similar. We followed Cochrane methodology, CHB Group methodology using Review Manager 5 and Trial Sequential Analysis to perform meta-analysis (M-A), assessed bias risk of the trials, quality of evidence using GRADE. Results: Four RCT, at high bias risk, low quality of evidence, provided data for analysis: 254 participants at different stages of NAFLD received oral UDCA (median of 18 months), 256 ― placebo/no intervention; age 18 to 75 years. We found no evidence of effect on mortality (there were no deaths) and on histological parameters such as steatosis (MD -0.13; CI -0.40−0.13; participants 323; trials 3; I2=43%), fibrosis (MD 0.00; CI -0.00−0.22; participants 323; trials 3; I2=0%), and inflammation (MD -0.05; CI -0.20−0.10; participants 325; trials 3; I2=0%). Also we found no evidence for significant influence of UDCA on occurrence of serious adverse events (RR 1.45, 95% CI 0.65−3.21; participants 292; trials 2; I2=0%), adverse events (RR 1.52, 95% CI 0.73−3.16; participants 510; trials 4; I2=36%) neither with traditional M-A (random-effects), nor with TSA SAE (CI 0.56−2.91; participants 292; trials 2; I2=0%, D2=0%), AE (CI 0.77–2.21; participants 510; trials 4; I2=0%, D2=0%). There was no evidence of effect on cytolysis, but beneficial effect of UDCA on cholestasis (GGTP) (data from two trials only) (р0.0001). We found no data on quality of life. All the trials were funded by the industry. Conclusion: Based on the small number of trials at high risk of bias, low quality, despite the safety profile observed with our M-A, we can neither recommend nor reject the use of UDCA for people with NAFLD. Further trials with low risk of bias and high quality are required to assess the benefits and harms of UDCA.