Protease inhibitor-based triple therapy is highly effective for hepatitis C recurrence after liver transplant: a multicenter experience

Introduction. Hepatitis C (HCV) continues to be the leading indication for liver transplantation (LT). Sustained virological response (SVR) rates to pegylated interferon (PEG-IFN) and ribavirin (RBV) therapy for recurrent HCV in Genotype 1 (G1) LT recipients have been disappointing (30-40%). Experie...

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Main Authors: Nabiha Faisal, MD, FCPS, Eric M. Yoshida, Marc Bilodeau, Philip Wong, Mang Ma, Kelly W. Burak, Bandar Al-Judaibi, Eberhard L. Renner, Leslie B. Lilly
Format: Article
Language:English
Published: Elsevier 2014-09-01
Series:Annals of Hepatology
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1665268119312529
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spelling doaj-844f8a7d86274a84abe445e26c0ea2e52021-06-09T05:53:50ZengElsevierAnnals of Hepatology1665-26812014-09-01135525532Protease inhibitor-based triple therapy is highly effective for hepatitis C recurrence after liver transplant: a multicenter experienceNabiha Faisal, MD, FCPS0Eric M. Yoshida1Marc Bilodeau2Philip Wong3Mang Ma4Kelly W. Burak5Bandar Al-Judaibi6Eberhard L. Renner7Leslie B. Lilly8Toronto General Hospital, University of Toronto. Ontario; Correspondence and reprint request:University of British Columbia and Vancouver General Hospital, QuebecUniversity of Montreal, QuebecMcGill University, QuebecUniversity of Alberta., London. Ontario, CanadaUniversity of Calgary., London. Ontario, CanadaWestern University, London. Ontario, CanadaToronto General Hospital, University of Toronto. OntarioToronto General Hospital, University of Toronto. OntarioIntroduction. Hepatitis C (HCV) continues to be the leading indication for liver transplantation (LT). Sustained virological response (SVR) rates to pegylated interferon (PEG-IFN) and ribavirin (RBV) therapy for recurrent HCV in Genotype 1 (G1) LT recipients have been disappointing (30-40%). Experience with triple therapy using protease inhibitors (PI) boceprevir (BOC), telaprevir (TVR) in these patients has been limited.Material and methods. This national multicenter retrospective study included 76 patients (64 male, mean age 57 ± 6 years), treated for G1 HCV recurrence with either BOC (n = 41) or TVR (n = 35), who were non-responders or relapsers (n = 54), treatment naïve (n = 22) or had fibrosing cholestatic HCV (n = 3). 53 patients were on cyclosporine, 22 on tacrolimus and one patient on prednisone alone.Results. On treatment virologic response was observed in 84% (64/76), 83% in BOC and 85% in TVR group. A higher week 4 response after starting triple therapy (RVR) was noted in TVR group 25/35 (81%) as compared to BOC group 26/41 (63%); p value = 0.02. The end of treatment response was 78% and 75% in BOC and TVR group, respectively. SVR 12 weeks after treatment discontinuation was observed in 59.5% (22/37); 58.3% in the BOC group and 61.5% in TVR group. Treatment was discontinued early in 23 patients (serious adverse effects n = 19, treatment failure n = 4). Infections occurred in 5 patients with 2 deaths (all in BOC). Anemia was the most common side effect (n = 55, 72%) requiring erythropoietin and RBV dose reduction. In the BOC group, cyclosporine dose reduction was 2.2 ± 1.0 fold and 8.6 ± 2.4 fold with tacrolimus. In TVR group, dose reduction was 3.0 ± 1.4 with cyclosporine and 12 ± 5.7 fold with tacrolimus. Conclusions. PI-based triple therapy appears more effective in producing HCV-RNA clearance than dual therapy. Tolerability is a serious issue and drug-drug interactions are manageable with close monitoring.http://www.sciencedirect.com/science/article/pii/S1665268119312529BoceprevirTelaprevirSustained virological responseEarly virological responseDrug-drug interaction
collection DOAJ
language English
format Article
sources DOAJ
author Nabiha Faisal, MD, FCPS
Eric M. Yoshida
Marc Bilodeau
Philip Wong
Mang Ma
Kelly W. Burak
Bandar Al-Judaibi
Eberhard L. Renner
Leslie B. Lilly
spellingShingle Nabiha Faisal, MD, FCPS
Eric M. Yoshida
Marc Bilodeau
Philip Wong
Mang Ma
Kelly W. Burak
Bandar Al-Judaibi
Eberhard L. Renner
Leslie B. Lilly
Protease inhibitor-based triple therapy is highly effective for hepatitis C recurrence after liver transplant: a multicenter experience
Annals of Hepatology
Boceprevir
Telaprevir
Sustained virological response
Early virological response
Drug-drug interaction
author_facet Nabiha Faisal, MD, FCPS
Eric M. Yoshida
Marc Bilodeau
Philip Wong
Mang Ma
Kelly W. Burak
Bandar Al-Judaibi
Eberhard L. Renner
Leslie B. Lilly
author_sort Nabiha Faisal, MD, FCPS
title Protease inhibitor-based triple therapy is highly effective for hepatitis C recurrence after liver transplant: a multicenter experience
title_short Protease inhibitor-based triple therapy is highly effective for hepatitis C recurrence after liver transplant: a multicenter experience
title_full Protease inhibitor-based triple therapy is highly effective for hepatitis C recurrence after liver transplant: a multicenter experience
title_fullStr Protease inhibitor-based triple therapy is highly effective for hepatitis C recurrence after liver transplant: a multicenter experience
title_full_unstemmed Protease inhibitor-based triple therapy is highly effective for hepatitis C recurrence after liver transplant: a multicenter experience
title_sort protease inhibitor-based triple therapy is highly effective for hepatitis c recurrence after liver transplant: a multicenter experience
publisher Elsevier
series Annals of Hepatology
issn 1665-2681
publishDate 2014-09-01
description Introduction. Hepatitis C (HCV) continues to be the leading indication for liver transplantation (LT). Sustained virological response (SVR) rates to pegylated interferon (PEG-IFN) and ribavirin (RBV) therapy for recurrent HCV in Genotype 1 (G1) LT recipients have been disappointing (30-40%). Experience with triple therapy using protease inhibitors (PI) boceprevir (BOC), telaprevir (TVR) in these patients has been limited.Material and methods. This national multicenter retrospective study included 76 patients (64 male, mean age 57 ± 6 years), treated for G1 HCV recurrence with either BOC (n = 41) or TVR (n = 35), who were non-responders or relapsers (n = 54), treatment naïve (n = 22) or had fibrosing cholestatic HCV (n = 3). 53 patients were on cyclosporine, 22 on tacrolimus and one patient on prednisone alone.Results. On treatment virologic response was observed in 84% (64/76), 83% in BOC and 85% in TVR group. A higher week 4 response after starting triple therapy (RVR) was noted in TVR group 25/35 (81%) as compared to BOC group 26/41 (63%); p value = 0.02. The end of treatment response was 78% and 75% in BOC and TVR group, respectively. SVR 12 weeks after treatment discontinuation was observed in 59.5% (22/37); 58.3% in the BOC group and 61.5% in TVR group. Treatment was discontinued early in 23 patients (serious adverse effects n = 19, treatment failure n = 4). Infections occurred in 5 patients with 2 deaths (all in BOC). Anemia was the most common side effect (n = 55, 72%) requiring erythropoietin and RBV dose reduction. In the BOC group, cyclosporine dose reduction was 2.2 ± 1.0 fold and 8.6 ± 2.4 fold with tacrolimus. In TVR group, dose reduction was 3.0 ± 1.4 with cyclosporine and 12 ± 5.7 fold with tacrolimus. Conclusions. PI-based triple therapy appears more effective in producing HCV-RNA clearance than dual therapy. Tolerability is a serious issue and drug-drug interactions are manageable with close monitoring.
topic Boceprevir
Telaprevir
Sustained virological response
Early virological response
Drug-drug interaction
url http://www.sciencedirect.com/science/article/pii/S1665268119312529
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