Audrey Coilly1, Bruno Roche1, Jérôme Dumortier2, Vincent Leroy3, Danielle Botta-Fridlund4, Sylvie Radenne5, Georges-Philippe Pageaux6, Si-Nafaa Si-Ahmed7, Olivier Guillaud2, Teresa Maria Antonini8, Stéphanie Haïm-Boukobza9, Anne-Marie Roque-Afonso9, Didier Samuel1, Jean-Charles Duclos-Vallée10. 1. AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif F-94800, France; Université Paris-Sud, UMR-S 785, Villejuif F-94800, France; Inserm, Unité 785, Villejuif F-94800, France; Hepatinov, Villejuif F-94800, France. 2. Hôpital Edouard Herriot, Unité de transplantation hépatique, Lyon F-69400, France. 3. CHU de Grenoble, Clinique universitaire d'hépato-gastroentérologie, Grenoble F-38000, France; Inserm, Unité 823, Grenoble F-38000, France. 4. CHU Conception, Service d'hépato-gastroentérologie, Marseille F-13005, France. 5. Hôpital de la Croix Rousse, Service de transplantation hépatique, Lyon F-69300, France; Université Claude Bernard Lyon 1, Lyon F-69000, France. 6. CHU Saint-Eloi, Département hépato-gastroentérologie et transplantation hépatique, Montpellier F-34200, France; Université Montpellier 1, Montpellier F-34000, France. 7. Hôpital de la Croix Rousse, Service de transplantation hépatique, Lyon F-69300, France. 8. AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif F-94800, France; Hepatinov, Villejuif F-94800, France. 9. Université Paris-Sud, UMR-S 785, Villejuif F-94800, France; Inserm, Unité 785, Villejuif F-94800, France; Hepatinov, Villejuif F-94800, France; AP-HP Hôpital Paul-Brousse, Laboratoire de Virologie, Villejuif F-94800, France. 10. AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif F-94800, France; Université Paris-Sud, UMR-S 785, Villejuif F-94800, France; Inserm, Unité 785, Villejuif F-94800, France; Hepatinov, Villejuif F-94800, France. Electronic address: jean-charles.duclos-vallee@pbr.aphp.fr.
Abstract
BACKGROUND & AIMS: Protease inhibitors (PI) with peginterferon/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 ± 11 years), treated with boceprevir (n=18) or telaprevir (n=19). The indication for therapy was HCV recurrence (fibrosis stage ≥F2 (n=31, 83%) or fibrosing cholestatic hepatitis (n=6, 16%). RESULTS: Eighteen patients were treatment-naive, five were relapsers and fourteen were non-responders to dual therapy after LT. Twenty-two patients received cyclosporine and fifteen 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 sixteen 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.
BACKGROUND & AIMS: Protease inhibitors (PI) with peginterferon/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 ± 11 years), treated with boceprevir (n=18) or telaprevir (n=19). The indication for therapy was HCV recurrence (fibrosis stage ≥F2 (n=31, 83%) or fibrosing cholestatic hepatitis (n=6, 16%). RESULTS: Eighteen patients were treatment-naive, five were relapsers and fourteen were non-responders to dual therapy after LT. Twenty-two patients received cyclosporine and fifteen 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 sixteen 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.
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