title: Sustained virological response to antiviral therapy in a randomized trial of cyclosporine versus tacrolimus in liver transplant patients with recurrent hepatitis C infection.
abstract: BACKGROUND
  Choice of calcineurin inhibitor may influence response to antiviral therapy in liver transplant patients with hepatitis C virus (HCV) infection.
  
  
  METHODS
  In a randomized, multicenter, 80-week trial, liver transplant recipients (>6 months and £10 years post-transplant) with recurrent HCV infection received cyclosporine (n=50) or tacrolimus (n=42) with a 48-week course of pegylated interferon (peg-IFNα2a) and ribavirin. Twenty-three patients in each group completed the trial on study medication. The primary endpoint was sustained virological response (SVR) 24 weeks after the end of antiviral therapy, for which 43 patients were eligible for analysis.
  
  
  RESULTS
  The rate of SVR was 60.0% (12/20) with cyclosporine and 43.5% (10/23) with tacrolimus (adjusted odds ratio 1.85; 95% CI 0.53-6.43; p=0.331). There were no significant intergroup differences for rapid or early virological response, relapse, HCV RNA viral load, or fibrosis progression. One cyclosporine-treated patient experienced acute rejection. One patient died in each group. Adverse events, treatment-related adverse events, and serious adverse events were similar between groups.
  
  
  CONCLUSIONS
  Since fewer patients were recruited than planned (92 versus 355), the study was underpowered and robust conclusions cannot be drawn regarding the effect of cyclosporine and tacrolimus on virological responses to antiviral treatment for recurrent HCV after liver transplantation. However, as reported in other trials, SVR was higher in cyclosporine-treated patients.
authors.affiliation: Department of Hepatology and Gastroenterology, Hôpital Henri Mondor APHP, Université Paris Est Créteil, Créteil, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Duvoux
authors.affiliation: Department of Transplantation, Hospital Britanico de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Federico
authors.initials: F
authors.lastname: Villamil
authors.affiliation: Liver Transplant Program/Multiorgan Transplant Program, University Health Network, Toronto, Canada.
authors.forename: Eberhard L
authors.initials: EL
authors.lastname: Renner
authors.affiliation: Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Gian Luca
authors.initials: GL
authors.lastname: Grazi
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, University of Florida College of Medicine, Gainesville, FL, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Firpi
authors.affiliation: Department of Hepatology, Gastroenterology, and Liver Transplantation, Centre Hospitalier Universitaire (CHU) Saint Eloi, Montpellier, France.
authors.forename: Georges
authors.initials: G
authors.lastname: Pageaux
authors.affiliation: Department of Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland.
authors.forename: Beat
authors.initials: B
authors.lastname: Mulhaupt
authors.affiliation: Datamap GmbH, Freiburg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Schirm
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Rauer
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Peter
authors.initials: P
authors.lastname: Bernhardt
authors.affiliation: Multi Organ Transplant Program, University of Toronto Transplant Institute, Toronto, Canada.
authors.forename: Gary
authors.initials: G
authors.lastname: Levy
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D065095:Calcineurin Inhibitors / Q000627:therapeutic use; D016572:Cyclosporine / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016898:Interferon-alpha / Q000627:therapeutic use; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D016559:Tacrolimus / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D016572:Cyclosporine; C100416:peginterferon alfa-2a; D016559:Tacrolimus