Efficacy of antiviral therapy for hepatitis C after liver transplantation with cyclosporine and tacrolimus: A systematic review and meta-analysis

Authors

  • Rania Rabie,

    1. Liver Transplant Program/Multi-Organ Transplant Program, University Health Network/Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada
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  • Khalid Mumtaz,

    1. Liver Transplant Program/Multi-Organ Transplant Program, University Health Network/Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada
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  • Eberhard L. Renner

    Corresponding author
    1. Liver Transplant Program/Multi-Organ Transplant Program, University Health Network/Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada
    • Liver Transplant Program/Multi-Organ Transplant Program, University Health Network/Toronto General Hospital, University of Toronto, 585 University Avenue, NCSB 11C-1238, Toronto, Ontario M5G 2N2, Canada
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    • Telephone: 416-340-6821; FAX: 416-340-3126;


  • Eberhard L. Renner has served as a member of advisory boards for Astellas, Novartis, Roche, and Vertex; as a member of the scientific committee for the SUSTAIN multicenter clinical trial (Novartis); and as a speaker for Novartis. He has also received grant support from Novartis Canada and Roche Canada.

  • This work was supported by an unrestricted grant to Eberhard L. Renner from Novartis Canada.

Abstract

Cyclosporine A (CSA), but not tacrolimus (TAC), inhibits hepatitis C virus (HCV) replication in vitro. Clinical reports on the efficacy of interferon-α (IFNα)–based antiviral therapy (AVT) for recurrent HCV after liver transplantation (LT) with CSA and TAC are conflicting. Our aim was to assess whether AVT for recurrent HCV after LT is more effective with CSA or TAC. We performed an electronic database search (1995-2012) and a manual abstract search (2005-2012). The a priori defined eligibility criteria included the use of AVT for recurrent HCV with IFN (standard or pegylated) and ribavirin and the reporting of sustained virological response (SVR) rates with CSA and TAC (the primary outcome). Two authors identified and extracted data independently. Dichotomous data were expressed as relative risks (RRs) and 95% confidence intervals (CIs) with a random effects model. In all, 5058 references were retrieved, and 1 randomized controlled trial (RCT) and 17 observational studies (13 full-text articles) met the eligibility criteria; the meta-analysis was based on the latter studies. The pooled SVR rates were 42% (395/945) with CSA and 35% (471/1364) with TAC (RR = 1.18, 95% CI = 1.00-1.39, P = 0.05). Although the pooled data contained significant heterogeneity (I2 = 45%, P = 0.02), the SVR rates in the RCT were comparable (39% with CSA and 35% with TAC). Limiting the analysis to the 7 studies reporting on 40 or more patients in each group (with 1634 patients in all) favored CSA (RR = 1.23, 95% CI = 1.09-1.38, P < 0.001), and heterogeneity disappeared (I2 = 0%, P = 0.62). In conclusion, IFN-based AVT for recurrent HCV after LT seems marginally more effective with CSA versus TAC; the study heterogeneity, however, limits firm conclusions. Liver Transpl 19:36–48, 2013. © 2012 AASLD.

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