OBJECTIVES: First-generation protease-inhibitors (PIs) had suboptimal efficacy in GT-1 patients with advanced liver disease, and those who failed may need urgent retreatment. Our objective was to analyze the real-life efficacy of interferon (IFN)-free retreatment after PI-failure, and the role of genotypic-resistance-testing (GRT) in guiding retreatment choice. METHODS: In this multi-center observational study, patients retreated with IFN-free regimens after first-generation PI-failure (telaprevir-boceprevir-simeprevir) were included. Sustained-virological-response (SVR) was evaluated at week 12 of follow-up. GRT was performed by population-sequencing. RESULTS: After PI-failure, 121 patients (cirrhotic=86.8%) were retreated following 3 different strategies: A) with "GRT-guided" regimens (N=18); B) with "AASLD/EASL recommended, not GRT-guided" regimens (N=72); C) with "Not recommended, not GRT-guided" regimens (N=31). Overall SVR rate was 91%, but all 18 patients treated with "GRT-guided" regimens reached SVR (100%), despite heterogeneity in treatment-duration, PI- and RBV-inclusion, vs. 68/72 patients (94.4%) receiving "AASLD/EASL recommended, not GRT-guided" regimens. SVR was strongly reduced (77.4%) among the 31 patients who received a "not recommended, not GRT-guided regimen" (p-trend<0.01). Among 37 patients retreated with a PI, SVR rate was 89.2% (33/37). Four GT-1a cirrhotic patients failed an option (C) simeprevir-containing treatment; 3/4 had a baseline R155K NS3-RAS. All 7 patients treated with a paritaprevir-containing regimens reached SVR, regardless treatment-duration and performance of a baseline-GRT. CONCLUSION: retreatment of PI-experienced patients can induce maximal SVR rates in real-life. Baseline-GRT could help to optimize retreatment strategy, allowing also PIs to be reconsidered when chosen after a RASs evaluation.

Cento, V., Barbaliscia, S., Lenci, I., Ruggiero, T., Magni, C., Paolucci, S., et al. (2017). Optimal efficacy of interferon-free HCV retreatment after protease inhibitors failure in real life. CLINICAL MICROBIOLOGY AND INFECTION.

Optimal efficacy of interferon-free HCV retreatment after protease inhibitors failure in real life.

CENTO, VALERIA;PERNO, CARLO FEDERICO;CECCHERINI SILBERSTEIN, FRANCESCA;TETI, ELISABETTA;DI MAIO, VELIA CHIARA;BERTOLI, ALDO;SARRECCHIA, CESARE;ANDREONI, MASSIMO;ANGELICO, MARIO
2017

Abstract

OBJECTIVES: First-generation protease-inhibitors (PIs) had suboptimal efficacy in GT-1 patients with advanced liver disease, and those who failed may need urgent retreatment. Our objective was to analyze the real-life efficacy of interferon (IFN)-free retreatment after PI-failure, and the role of genotypic-resistance-testing (GRT) in guiding retreatment choice. METHODS: In this multi-center observational study, patients retreated with IFN-free regimens after first-generation PI-failure (telaprevir-boceprevir-simeprevir) were included. Sustained-virological-response (SVR) was evaluated at week 12 of follow-up. GRT was performed by population-sequencing. RESULTS: After PI-failure, 121 patients (cirrhotic=86.8%) were retreated following 3 different strategies: A) with "GRT-guided" regimens (N=18); B) with "AASLD/EASL recommended, not GRT-guided" regimens (N=72); C) with "Not recommended, not GRT-guided" regimens (N=31). Overall SVR rate was 91%, but all 18 patients treated with "GRT-guided" regimens reached SVR (100%), despite heterogeneity in treatment-duration, PI- and RBV-inclusion, vs. 68/72 patients (94.4%) receiving "AASLD/EASL recommended, not GRT-guided" regimens. SVR was strongly reduced (77.4%) among the 31 patients who received a "not recommended, not GRT-guided regimen" (p-trend<0.01). Among 37 patients retreated with a PI, SVR rate was 89.2% (33/37). Four GT-1a cirrhotic patients failed an option (C) simeprevir-containing treatment; 3/4 had a baseline R155K NS3-RAS. All 7 patients treated with a paritaprevir-containing regimens reached SVR, regardless treatment-duration and performance of a baseline-GRT. CONCLUSION: retreatment of PI-experienced patients can induce maximal SVR rates in real-life. Baseline-GRT could help to optimize retreatment strategy, allowing also PIs to be reconsidered when chosen after a RASs evaluation.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/07 - Microbiologia e Microbiologia Clinica
eng
Con Impact Factor ISI
Cirrhosis; DIrect acting antivirals; Genotypic resistance testing; HCVFailure; NS5A-inhibitors; Protease-inhibitors; Retreatment; hcv-resistance
http://www.sciencedirect.com/science/article/pii/S1198743X17302100
Cento, V., Barbaliscia, S., Lenci, I., Ruggiero, T., Magni, C., Paolucci, S., et al. (2017). Optimal efficacy of interferon-free HCV retreatment after protease inhibitors failure in real life. CLINICAL MICROBIOLOGY AND INFECTION.
Cento, V; Barbaliscia, S; Lenci, I; Ruggiero, T; Magni, C; Paolucci, S; Babudieri, S; Siciliano, M; Pasquazzi, C; Ciancio, A; Perno, C; Ceccherini-Silberstein, F; Micheli, V; Troshina, Y; Biliotti, E; Milana, M; Melis, M; Teti, E; Lambiase, L; Menzaghi, B; Nicolini, L; Marenco, S; Di Maio, V; Aragri, M; Pecchioli, A; Bertoli, A; Sarrecchia, C; Macera, M; Coppola, N; Puoti, M; Romagnoli, D; Pellicelli, A; Bonora, S; Novati, S; Baldanti, F; Ghisetti, V; Andreoni, M; Taliani, G; Rizzardini, G; Angelico, M
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/180637
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