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Improvement of ALT decay kinetics by all-oral HCV treatment: Role of NS5A inhibitors and differences with IFN-based regimens

Author

Listed:
  • Valeria Cento
  • Thi Huyen Tram Nguyen
  • Domenico Di Carlo
  • Elisa Biliotti
  • Laura Gianserra
  • Ilaria Lenci
  • Daniele Di Paolo
  • Vincenza Calvaruso
  • Elisabetta Teti
  • Maddalena Cerrone
  • Dante Romagnoli
  • Michela Melis
  • Elena Danieli
  • Barbara Menzaghi
  • Ennio Polilli
  • Massimo Siciliano
  • Laura Ambra Nicolini
  • Antonio Di Biagio
  • Carlo Federico Magni
  • Matteo Bolis
  • Francesco Paolo Antonucci
  • Velia Chiara Di Maio
  • Roberta Alfieri
  • Loredana Sarmati
  • Paolo Casalino
  • Sergio Bernardini
  • Valeria Micheli
  • Giuliano Rizzardini
  • Giustino Parruti
  • Tiziana Quirino
  • Massimo Puoti
  • Sergio Babudieri
  • Antonella D’Arminio Monforte
  • Massimo Andreoni
  • Antonio Craxì
  • Mario Angelico
  • Caterina Pasquazzi
  • Gloria Taliani
  • Jeremie Guedj
  • Carlo Federico Perno
  • Francesca Ceccherini-Silberstein

Abstract

Background: Intracellular HCV-RNA reduction is a proposed mechanism of action of direct-acting antivirals (DAAs), alternative to hepatocytes elimination by pegylated-interferon plus ribavirin (PR). We modeled ALT and HCV-RNA kinetics in cirrhotic patients treated with currently-used all-DAA combinations to evaluate their mode of action and cytotoxicity compared with telaprevir (TVR)+PR. Study design: Mathematical modeling of ALT and HCV-RNA kinetics was performed in 111 HCV-1 cirrhotic patients, 81 treated with all-DAA regimens and 30 with TVR+PR. Kinetic-models and Cox-analysis were used to assess determinants of ALT-decay and normalization. Results: HCV-RNA kinetics was biphasic, reflecting a mean effectiveness in blocking viral production >99.8%. The first-phase of viral-decline was faster in patients receiving NS5A-inhibitors compared to TVR+PR or sofosbuvir+simeprevir (p

Suggested Citation

  • Valeria Cento & Thi Huyen Tram Nguyen & Domenico Di Carlo & Elisa Biliotti & Laura Gianserra & Ilaria Lenci & Daniele Di Paolo & Vincenza Calvaruso & Elisabetta Teti & Maddalena Cerrone & Dante Romagn, 2017. "Improvement of ALT decay kinetics by all-oral HCV treatment: Role of NS5A inhibitors and differences with IFN-based regimens," PLOS ONE, Public Library of Science, vol. 12(5), pages 1-13, May.
    • Handle: RePEc:plo:pone00:0177352
    DOI: 10.1371/journal.pone.0177352
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