PLoS ONE (Jan 2015)

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

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

DOI
https://doi.org/10.1371/journal.pone.0138091
Journal volume & issue
Vol. 10, no. 9
p. e0138091

Abstract

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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.