Liver Transplant Program/Multi-Organ Transplant Program, University Health Network/Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada.
BACKGROUND AND AIMS:
Cyclosporine, but not tacrolimus, inhibits hepatitis C virus replication, in vitro. Clinical reports on the efficacy of interferon-alpha based antiviral therapy, for recurrent hepatitis C after liver transplantation on cyclosporine vs. tacrolimus, are conflicting. We aimed to assess whether antiviral therapy for recurrent hepatitis C post LT is more effective on cyclosporine than on tacrolimus.
We performed an electronic database (1995-2012) and manual abstract (2005-2012) search. A priori defined eligibility criteria included anti-viral therapy for recurrent hepatitis C with interferon (standard OR pegylated) AND ribavirin, and reporting of sustained virologic response rates on cyclosporine vs. tacrolimus (primary outcome). Two authors identified/extracted data independently. Dichotomous data was expressed as relative risk with 95% confidence intervals using a random effects model.
Of 5058 references retrieved, 1 randomized controlled trial and 17 observational studies (13 full-text papers) met eligibility criteria; the meta-analysis was based on the latter. Pooled sustained virologic response rates were 395/945 (42%) on cyclosporine compared to 471/1364 (35%) on tacrolimus (1.18; 1.00 - 1.39; p=0.05). While the pooled data contained significant heterogeneity (I(2) =45%; p=0.02), sustained virologic response rates in the randomized controlled trial compare favourably (cyclosporine: 39%; tacrolimus: 35%). Limiting the analysis to studies reporting on ≥40 patients in each group (n=7 studies/1634 patients) favoured cyclosporine (1.23; 1.09 - 1.38; p=0.0008) and heterogeneity disappeared (I(2) =0%; p=0.62).
Interferon based anti-viral therapy for recurrent hepatitis C post liver transplantation seems marginally more effective on cyclosporine than on tacrolimus; study heterogeneity, however, limits firm conclusions.