title: A network meta-analysis of the efficacy and side effects of UDCA-based therapies for primary sclerosing cholangitis.
abstract: OBJECTIVE
  Therapies for treatment of patients with primary sclerosing cholangitis (PSC) include administration of ursodeoxycholic acid (UDCA) alone, or combination with metronidazole (MTZ) or mycophenolate mofetil (MMF), respectively. However, the optimum regimen still remains inconclusive. We aimed to compare interventions in terms of patient mortality or liver transplantation (MOLT), progression of liver histological stage (POLHS), serum bilirubin, alkaline phosphatase (ALP) levels and adverse events (AE).
  
  
  METHODS
  We searched PubMed, Embase and the Cochrane Library for randomized controlled trials until 31, Jan 2015. We estimated hazard ratios (HRs), odds ratios (ORs) and mean difference (MD) between treatments on clinical outcomes. Sensitivity analyses based on the dose of UDCA, quality of trials or treatment duration were also performed.
  
  
  RESULTS
  Ten RCTs were included. Compared with UDCA plus MTZ, UDCA (HR 0.28, 95%CI 0.01-3.41), UDCA plus MMF (HR 0.08, 95%CI 0.00-4.18), or OBS (HR 0.28, 95%CI 0.01-3.98) all provided an increased risk of MOLT. UDCA provided a significant reduction in bilirubin and ALP levels compared with OBS (MD -13.92, P < 0.001; MD -484.34, P < 0.001; respectively). With respect to POLHS, although differing not significantly, UDCA plus MTZ had a tendency to improve LHS more than UDCA (OR 1.33), UDCA plus MMF (OR 3.24) or OBS (OR 1.08). Additionally, UDCA plus MTZ (MD -544.66, P < 0.001) showed a significant reduction in ALP levels compared with OBS, but appeared to be associated with more AEs compared with UDCA (OR 5.09), UDCA plus MMF (OR 4.80) or OBS (OR 7.21).
  
  
  CONCLUSIONS
  MTZ plus UDCA was the most effective therapy in survival rates and liver histological progression.
authors.affiliation: Department of Infection and Liver Diseases, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.|School of the First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, China.
authors.forename: Gui-Qi
authors.initials: GQ
authors.lastname: Zhu
authors.affiliation: Department of Infection and Liver Diseases, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.|Institute of Hepatology, Wenzhou Medical University, Wenzhou, China.
authors.forename: Ke-Qing
authors.initials: KQ
authors.lastname: Shi
authors.affiliation: Department of Infection and Liver Diseases, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.|Renji School of Wenzhou Medical University, Wenzhou ,China.
authors.forename: Gui-Qian
authors.initials: GQ
authors.lastname: Huang
authors.affiliation: Department of Infection and Liver Diseases, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.|School of the First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, China.
authors.forename: Li-Ren
authors.initials: LR
authors.lastname: Wang
authors.affiliation: Department of Infection and Liver Diseases, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.|Renji School of Wenzhou Medical University, Wenzhou ,China.
authors.forename: Yi-Qian
authors.initials: YQ
authors.lastname: Lin
authors.affiliation: Global Medicines Development, AstraZeneca R&D, Loughborough, United Kingdom.
authors.forename: Martin
authors.initials: M
authors.lastname: Braddock
authors.affiliation: Department of Infection and Liver Diseases, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.|Institute of Hepatology, Wenzhou Medical University, Wenzhou, China.
authors.forename: Yong-Ping
authors.initials: YP
authors.lastname: Chen
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Meng-Tao
authors.initials: MT
authors.lastname: Zhou
authors.affiliation: Department of Infection and Liver Diseases, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.|Institute of Hepatology, Wenzhou Medical University, Wenzhou, China.
authors.forename: Ming-Hua
authors.initials: MH
authors.lastname: Zheng
mesh_terms: D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D001663:Bilirubin / Q000097:blood; D002756:Cholagogues and Choleretics / Q000008:administration & dosage; D015209:Cholangitis, Sclerosing / Q000628:therapy*; D018450:Disease Progression; D006801:Humans; D008099:Liver / Q000473:pathology; D016031:Liver Transplantation; D008795:Metronidazole / Q000008:administration & dosage*; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016017:Odds Ratio; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D002756:Cholagogues and Choleretics; D008795:Metronidazole; D014580:Ursodeoxycholic Acid; D000469:Alkaline Phosphatase; D009173:Mycophenolic Acid; D001663:Bilirubin
keywords: Pathology Section; adverse events; clinical efficacy; intervention; network meta-analysis; primary sclerosing cholangitis