Published 2017
| Version v1
Publication
Improvement of ALT decay kinetics by all-oral HCV treatment: Role of NS5A inhibitors and differences with IFN-based regimens
Creators
- Cento, Valeria
- Nguyen, Thi Huyen Tram
- Di Carlo, Domenico
- Biliotti, Elisa
- Gianserra, Laura
- Lenci, Ilaria
- Di Paolo, Daniele
- Calvaruso, Vincenza
- Teti, Elisabetta
- Cerrone, Maddalena
- Romagnoli, Dante
- Melis, Michela
- Danieli, Elena
- Menzaghi, Barbara
- Polilli, Ennio
- Siciliano, Massimo
- NICOLINI, LAURA AMBRA
- Di Biagio, Antonio
- Magni, Carlo Federico
- Bolis, Matteo
- Antonucci, Francesco Paolo
- Di Maio, Velia Chiara
- Alfieri, Roberta
- Sarmati, Loredana
- Casalino, Paolo
- Bernardini, Sergio
- Micheli, Valeria
- Rizzardini, Giuliano
- Parruti, Giustino
- Quirino, Tiziana
- Puoti, Massimo
- Babudieri, Sergio
- Monforte, Antonella D'Arminio
- Andreoni, Massimo
- Craxì, Antonio
- Angelico, Mario
- Pasquazzi, Caterina
- Taliani, Gloria
- Guedj, Jeremie
- Perno, Carlo Federico
- Ceccherini Silberstein, Francesca
Contributors
Others:
- Cento, Valeria
- Nguyen, Thi Huyen Tram
- Di Carlo, Domenico
- Biliotti, Elisa
- Gianserra, Laura
- Lenci, Ilaria
- Di Paolo, Daniele
- Calvaruso, Vincenza
- Teti, Elisabetta
- Cerrone, Maddalena
- Romagnoli, Dante
- Melis, Michela
- Danieli, Elena
- Menzaghi, Barbara
- Polilli, Ennio
- Siciliano, Massimo
- Nicolini, LAURA AMBRA
- Di Biagio, Antonio
- Magni, Carlo Federico
- Bolis, Matteo
- Antonucci, Francesco Paolo
- Di Maio, Velia Chiara
- Alfieri, Roberta
- Sarmati, Loredana
- Casalino, Paolo
- Bernardini, Sergio
- Micheli, Valeria
- Rizzardini, Giuliano
- Parruti, Giustino
- Quirino, Tiziana
- Puoti, Massimo
- Babudieri, Sergio
- Monforte, Antonella D'Arminio
- Andreoni, Massimo
- Craxì, Antonio
- Angelico, Mario
- Pasquazzi, Caterina
- Taliani, Gloria
- Guedj, Jeremie
- Perno, Carlo Federico
- Ceccherini Silberstein, Francesca
Description
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<0.001), reflecting higher efficacy in blocking assembly/secretion. The second-phase, noted δ and attributed to infected-cell loss, was faster in patients receiving TVR+PR or sofosbuvir+simeprevir compared to NS5A-inhibitors (0.27 vs 0.21 d-1, respectively, p = 0.0012). In contrast the rate of ALT-normalization, noted λ, was slower in patients receiving TVR+PR or sofosbuvir+simeprevir compared to NS5A-inhibitors (0.17 vs 0.27 d-1, respectively, p<0.001). There was no significant association between the second-phase of viral-decline and ALT normalization rate and, for a given level of viral reduction, ALT-normalization was more profound in patients receiving DAA, and NS5A in particular, than TVR+PR. Conclusions: Our data support a process of HCV-clearance by all-DAA regimens potentiated by NS5A-inhibitor, and less relying upon hepatocyte death than IFN-containing regimens. This may underline a process of "cell-cure" by DAAs, leading to a fast improvement of liver homeostasis.
Additional details
Identifiers
- URL
- http://hdl.handle.net/11567/873895
- URN
- urn:oai:iris.unige.it:11567/873895
Origin repository
- Origin repository
- UNIGE