Journal Article

Multicenter Experience with Boceprevir or Telaprevir to Treat Hepatitis C Recurrence after Liver Transplantation: When Present Becomes Past, What Lessons for Future?

Botta-Fridlund, Danielle, Duclos-Vallée, Jean-Charles, Agostini, Hélène, Guillaud, Olivier, Samuel, Didier, Leroy, Vincent, Debette-Gratien, Maryline, Coilly, Audrey, Dumortier, Jérôme, Durand, François, Duvoux, Christophe, De Ledinghen, Victor, Pageaux, Georges-Philippe, Latournerie, Marianne, Saouli, Anne-Catherine, Roche, Bruno, Calmus, Yvon, Alric, Laurent, Moreno, Christophe, Antonini, Teresa Maria, Radenne, Sylvie, Giostra, Emiliano, Lebray, Pascal

2015

Overview

First generation protease inhibitors (PI) with peg-interferon (PEG-IFN) and ribavirin (RBV) have been the only therapy available for hepatitis C virus (HCV) genotype 1 infection in most countries for 3 years. We have investigated the efficacy and tolerance of this triple therapy in transplanted patients experiencing a recurrence of HCV infection on the liver graft. This cohort study enrolled 81 liver transplant patients (Male: 76%, mean age: 55.8±9.7 years) with severe HCV recurrence (F3 or F4: n = 34 (42%), treatment experienced: n = 44 (54%)), treated with boceprevir (n = 36; 44%) or telaprevir (n = 45; 56%). We assessed the percentages of patients with sustained virological responses 24 weeks after therapy (SVR24), and safety. The SVR24 rate was 47% (telaprevir: 42%; boceprevir: 53%, P = ns). At baseline, a normal bilirubin level (p = 0.0145) and albumin level >35g/L (p = 0.0372) and an initial RBV dosage of ≥800 mg/day (p = 0.0033) predicted SVR24. During treatment, achieving an early virological response after 12 weeks was the strongest independent factor to predict SVR24 (p<0.0001). A premature discontinuation of anti-HCV therapy due to a serious adverse event (SAE) was observed in 22 patients (27%). Hematological toxicity, infections and deaths were observed in 95%, 28% and 7% of patients, respectively. A history of post-LT antiviral therapy and thrombocytopenia (<50G/L) during treatment were both independent predictors of the occurrence of infections or SAE (p = 0.0169 and p = 0.011). The use of first generation PI after liver transplantation enabled an SVR24 rate of 47% in genotype 1 patients, but induced a high rate of SAE. The identification of predictive factors for a response to treatment, and the occurrence of SAE, have enabled us to establish limits for the use of this anti-HCV therapy in the transplant setting.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adult / Aged / Anemia - chemically induced / Antiviral agents / Antiviral Agents - adverse effects / Antiviral Agents - pharmacology / Antiviral drugs / Bilirubin / Biological response modifiers / Biopsy / Combined Modality Therapy / Complications and side effects / Drug dosages / Drug Therapy, Combination / Female / Gastroenterology / Genotype / Genotypes / Hematology / Hepacivirus - drug effects / Hepacivirus - enzymology / Hepacivirus - physiology / Hepatitis / Hepatitis C / Hepatitis C - genetics / Hepatitis C - therapy / Hepatitis C - virology / Hepatitis C virus / Hepatology / Host-Pathogen Interactions - drug effects / Humans / Immunological tolerance / Infection / Infections / Interferon / Interferon-alpha - adverse effects / Interferon-alpha - pharmacology / Life Sciences / Liver / Liver cancer / Liver diseases / Liver transplantation / Liver Transplantation - methods / Liver transplants / Male / Medical research / Middle Aged / Multivariate Analysis / Oligopeptides - adverse effects / Oligopeptides - pharmacology / Patients / Polyethylene Glycols - adverse effects / Polyethylene Glycols - pharmacology / Postoperative Period / Proline - adverse effects / Proline - analogs & derivatives / Proline - pharmacology / Prospective Studies / Protease inhibitors / Protease Inhibitors - adverse effects / Protease Inhibitors - pharmacology / Proteases / Proteinase inhibitors / Recombinant Proteins - adverse effects / Recombinant Proteins - pharmacology / Recurrence / Recurrence (Disease) / Ribavirin / Therapy / Thrombocytopenia / Thrombocytopenia - chemically induced / Toxicity / Transplantation / Transplants & implants / Treatment Outcome / Viruses