Oncotarget

Research Papers: Pathology:

A network meta-analysis of the efficacy and side effects of udca-based therapies for primary sclerosing cholangitis

Gui-Qi Zhu, Ke-Qing Shi, Gui-Qian Huang, Li-Ren Wang, Yi-Qian Lin, Martin Braddock, Yong-Ping Chen, Meng-Tao Zhou and Ming-Hua Zheng _

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Oncotarget. 2015; 6:26757-26769. https://doi.org/10.18632/oncotarget.5610

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Abstract

Gui-Qi Zhu1,2,*, Ke-Qing Shi1,3,*, Gui-Qian Huang1,4, Li-Ren Wang1,2, Yi-Qian Lin1,4, Martin Braddock5, Yong-Ping Chen1,3, Meng-Tao Zhou6 and Ming-Hua Zheng1,3

1 Department of Infection and Liver Diseases, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

2 School of the First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, China

3 Institute of Hepatology, Wenzhou Medical University, Wenzhou China

4 Renji School of Wenzhou Medical University, Wenzhou China

5 Global Medicines Development, AstraZeneca R&D, Loughborough, United Kingdom

6 Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

* Co-first author

Correspondence to:

Ming-Hua Zheng, email:

Meng-Tao Zhou, email:

Keywords: primary sclerosing cholangitis, intervention, adverse events, clinical efficacy, network meta-analysis, Pathology Section

Received: June 20, 2015 Accepted: August 28, 2015 Published: September 10, 2015

Abstract

Objectives: 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.


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