The Effect of Cyclosporine A versus Tacrolimus on the Response to Antiviral Treatment after HCV Recurrence in Recipients of Living Donor Liver Transplantation

Abstract

Background: Hepatitis C virus (HCV) infection is a major public health burden in Egypt. Liver transplantation (LT) is considered a therapeutic option in patients with end-stage liver disease (ESLD) but post-transplant HCV recurrence is very common, and up to 90% of these patients subsequently develop chronic HCV disease. Antiviral therapy (AVT) has been associated with improved survival in LT recipients who manage to achieve a sustained virological response (SVR).The influence of immunosuppression on the response to AVT for recurrent HCV infection post LT remains controversial, especially for the rarely investigated genotype 4. Aim: To compare the impact of the two widely used calcineurin inhibitors (CNIs) (cyclosporine A (CsA) and tacrolimus (Tac)) on the therapeutic response to three different AVT regimens. Patients and Methods: A cohort, prospective, two-centre study was conducted on 126 Egyptian living donor liver transplantation (LDLT) recipients with recurrent HCV infection, participants were categorized in to three groups according to AVT. Group one received pegylated interferon (peg IFN-α 2a) and ribavirin (RBV) (n= 44), group two received the direct antiviral agent (DAA) sofosbuvir plus RBV (n=52) and group three received (other DAAs) daclatasvir, sofosbuvir plus RBV(n=30) each group was further subdivided according to the primary immunosuppression (CsA or Tac). The SVR and relapse rates were considered the primary therapeutic outcomes of AVT. The virological response guided therapy end points for AVT were considered the secondary outcomes. Results: No significant intergroup differences were observed in the achievement of primary and secondary outcomes.The SVR rates in IFN based regimen were (75% and 66.7% in CsA and Tac users respectively; p=0.546) and in DAAs, were (81.2% and 83% respectively; p=0.843). In group II; the SVR rates were (70% and 75.9% in CsA and Tac usesrs respectively; p=0.648) and in group III; the SVR rates were (100% and 94.4 % in CsA and Tac usesrs respectively; p=0.406). Conclusion: According to the result in this study, cyclosporine A did not offer an advantage over Tacrolimus regarding the response to different AVT regimens including (peg –IFN based regimen and DAAs based regimen) after HCV genotype- 4 recurrence in LDLT recipients. Keywords: Antiviral therapy, Cyclosporine A, Hepatitis C genotype -4, Liver transplantation, Sustained virological response, Tacrolimus.