Safety and Efficacy of Protease Inhibitors to Treat Hepatitis C After Liver Transplantation: a Multicenter Experience

Journal of Hepatology

Article in Press

Coilly Audrey, Roche Bruno, Dumortier Jérôme, Leroy Vincent, Botta-Fridlund Danielle, Radenne Sylvie, Pageaux Georges-Philippe, Si-Ahmed Si-Nafaa, Guillaud Olivier, Antonini Teresa Maria, Haim-Boukobza Stéphanie, Roque-Afonso Anne-Marie, Samuel Didier, Duclos-Vallee Jean-Charles

Received 18 February 2013; received in revised form 16 July 2013; accepted 15 August 2013. published online 30 August 2013.
Accepted Manuscript

Abstract

Background

Protease inhibitors (PI) with peg-interferon/ribavirin have significantly improved SVR rates in HCV G1 patients. Their use to treat HCV recurrence after liver transplantation (LT) is a challenge.

Methods

This cohort study included 37 liver transplant recipients (male: 92%, age 57±11years), treated with boceprevir (n=18) or telaprevir (n=19). The indication for therapy was HCV recurrence (fibrosis stage > than or equal to F2 (n=31, 83%) or fibrosing cholestatic hepatitis (n=6, 16%).

Results

Eighteen patients were treatment-naive, five were relapsers and 14 were non-responders to dual therapy after LT. Twenty-two patients received cyclosporine and 15 tacrolimus. After 12 weeks of PI therapy, a complete virological response was obtained in 89% of patients treated with boceprevir, and 58% with telaprevir (P=0.06). The end of treatment virological response rate was 72% (13/18) in the boceprevir group and 40% (4/10) in the telaprevir group (P=0.125). A sustained virological response 12 weeks after treatment discontinuation was observed in 20% (1/5) and 71% (5/7) of patients in the telaprevir and boceprevir groups, respectively (P=0.24). Treatment was discontinued in 16 patients (treatment failures (n=11), adverse events (n=5)). Infections occurred in ten patients (27%), with three fatal outcomes (8%). The most common adverse effect was anemia (n=34, 92%), treated with erythropoietin and/or a ribavirin dose reduction; thirteen patients (35%) received red blood cell transfusions. The cyclosporine dose was reduced by 1.8±1.1-fold and 3.4±1.0-fold with boceprevir and telaprevir, respectively. The tacrolimus dose was reduced by 5.2±1.5-fold with boceprevir and 23.8±18.2-fold with telaprevir.

Conclusions

Our results suggest that triple therapy is effective in LT recipients, particularly those experiencing a severe recurrence. The occurrence of anemia and drug-drug interactions, and the risk of infections, require close monitoring.

Keywords: Abbreviations

Keywords: ALT, alanine aminotransferase, AFEF, French Association for the Study of the Liver, AUC, area under the curve, BID, twice daily (bis in die), BOC, boceprevir, cEVR, complete early virological response, CNI, calcineurin inhibitors, CYP, cytochrome P450, EPO, erythropoietin, EOT, end of treatment response rate, EVR, early virological response, F, female, FCH, fibrosing cholestatic hepatitis, G1, genotype 1, GGT, gamma-glutamyl transferase, HBV, hepatitis B virus, HCC, hepatocellular carcinoma, HCV, hepatitis C virus, HIV, human immunodeficiency virus, IL, interleukin, INR, International Normalized Ratio, IS, immunosuppressive drugs, Kg, Kilogram, LT, liver transplantation, M, male, MELD, Model for End-stage Liver Disease, MMF, mycophenolate mofetil, NA, not available, NR, non-response, PCR, polymerase chain reaction, PEG-IFN, pegylated interferon, PI, protease inhibitors, QD, once a day (quaque die), RBV, ribavirin, RVR, rapid virological response, SVR12, sustained virological response 12 weeks after the end of therapy, TBC, trough blood concentration, TID, three times a day (ter in die), TVR, telaprevir, VB, virological breakthrough, VL, viral load, VR, virological response.

Keywords: Boceprevir, Drug-drug interaction, Early virological response, HCV recurrence, Liver transplantation, Protease inhibitors, Sustained virological response, Telaprevir

PII: S0168-8278(13)00613-2

doi:10.1016/j.jhep.2013.08.018

© 2013 Published by Elsevier Inc.

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