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

V. Cento; S. Barbaliscia; I. Lenci; T. Ruggiero; C. F. Magni; S. Paolucci; S. Babudieri; M. Siciliano; C. Pasquazzi; A. Ciancio; C. F. Perno; F. Ceccherini-Silberstein; V. Micheli; Y. Troshina; E. Biliotti; M. Milana; M. Melis; E. Teti; L. Lambiase; B. Menzaghi; L. A. Nicolini; S. Marenco; V. C. Di Maio; M. Aragri; A. Pecchioli; A. Bertoli; C. Sarrecchia; M. Macera; N. Coppola; M. Puoti; D. Romagnoli; A. Pellicelli; S. Bonora; S. Novati; F. Baldanti; V. Ghisetti; M. Andreoni; G. Taliani; G. Rizzardini; M. Angelico; on behalf of; the HCV retreatment team VIRONET-C study group

doi:10.1016/j.cmi.2017.04.005

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

V. Cento, S. Barbaliscia, I. Lenci, T. Ruggiero, C. F. Magni, S. Paolucci, S. Babudieri, M. Siciliano, C. Pasquazzi, A. Ciancio, C. F. Perno, F. Ceccherini-Silberstein, V. Micheli, Y. Troshina, E. Biliotti, M. Milana, M. Melis, E. Teti, L. Lambiase, B. MenzaghiL. A. Nicolini, S. Marenco, V. C. Di Maio, M. Aragri, A. Pecchioli, A. Bertoli, C. Sarrecchia, M. Macera, N. Coppola, M. Puoti, D. Romagnoli, A. Pellicelli, S. Bonora, S. Novati, F. Baldanti, V. Ghisetti, M. Andreoni, G. Taliani, G. Rizzardini, M. Angelico, on behalf of, the HCV retreatment team VIRONET-C study group

Research output: Contribution to journal › Article

Abstract

Objectives First-generation protease-inhibitors (PIs) have suboptimal efficacy in GT-1 patients with advanced liver disease, and patients experiencing treatment failure may require urgent retreatment. Our objective was to analyse 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-centre 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 three 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, use of PI and ribavirin, versus 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 <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; three out of four had a baseline R155K NS3-RAS. All seven patients treated with paritaprevir-containing regimens reached SVR, regardless of 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 PIs to be reconsidered when chosen after a RASs evaluation.

Original language	English
Pages (from-to)	777.e1-777.e4
Journal	Clinical Microbiology and Infection
Volume	23
Issue number	10
DOIs	https://doi.org/10.1016/j.cmi.2017.04.005
Publication status	Published - Oct 1 2017

Keywords

Cirrhosis
Direct acting antivirals
Genotypic resistance testing
HCV failure
HCV resistance
NS5A-inhibitors
Protease-inhibitors
Retreatment

ASJC Scopus subject areas

Microbiology (medical)
Infectious Diseases

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Cento, V., Barbaliscia, S., Lenci, I., Ruggiero, T., Magni, C. F., Paolucci, S., Babudieri, S., Siciliano, M., Pasquazzi, C., Ciancio, A., Perno, C. F., Ceccherini-Silberstein, F., Micheli, V., Troshina, Y., Biliotti, E., Milana, M., Melis, M., Teti, E., Lambiase, L., ... the HCV retreatment team VIRONET-C study group (2017). Optimal efficacy of interferon-free HCV retreatment after protease inhibitor failure in real life. Clinical Microbiology and Infection, 23(10), 777.e1-777.e4. https://doi.org/10.1016/j.cmi.2017.04.005

Optimal efficacy of interferon-free HCV retreatment after protease inhibitor failure in real life. / Cento, V.; Barbaliscia, S.; Lenci, I.; Ruggiero, T.; Magni, C. F.; Paolucci, S.; Babudieri, S.; Siciliano, M.; Pasquazzi, C.; Ciancio, A.; Perno, C. F.; Ceccherini-Silberstein, F.; Micheli, V.; Troshina, Y.; Biliotti, E.; Milana, M.; Melis, M.; Teti, E.; Lambiase, L.; Menzaghi, B.; Nicolini, L. A.; Marenco, S.; Di Maio, V. C.; 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.; on behalf of; the HCV retreatment team VIRONET-C study group.

In: Clinical Microbiology and Infection, Vol. 23, No. 10, 01.10.2017, p. 777.e1-777.e4.

Research output: Contribution to journal › Article

Cento, V, Barbaliscia, S, Lenci, I, Ruggiero, T, Magni, CF, Paolucci, S, Babudieri, S, Siciliano, M, Pasquazzi, C, Ciancio, A, Perno, CF, Ceccherini-Silberstein, F, Micheli, V, Troshina, Y, Biliotti, E, Milana, M, Melis, M, Teti, E, Lambiase, L, Menzaghi, B, Nicolini, LA, Marenco, S, Di Maio, VC, 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, on behalf of & the HCV retreatment team VIRONET-C study group 2017, 'Optimal efficacy of interferon-free HCV retreatment after protease inhibitor failure in real life', Clinical Microbiology and Infection, vol. 23, no. 10, pp. 777.e1-777.e4. https://doi.org/10.1016/j.cmi.2017.04.005

Cento, V. ; Barbaliscia, S. ; Lenci, I. ; Ruggiero, T. ; Magni, C. F. ; Paolucci, S. ; Babudieri, S. ; Siciliano, M. ; Pasquazzi, C. ; Ciancio, A. ; Perno, C. F. ; Ceccherini-Silberstein, F. ; Micheli, V. ; Troshina, Y. ; Biliotti, E. ; Milana, M. ; Melis, M. ; Teti, E. ; Lambiase, L. ; Menzaghi, B. ; Nicolini, L. A. ; Marenco, S. ; Di Maio, V. C. ; 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. ; on behalf of ; the HCV retreatment team VIRONET-C study group. / Optimal efficacy of interferon-free HCV retreatment after protease inhibitor failure in real life. In: Clinical Microbiology and Infection. 2017 ; Vol. 23, No. 10. pp. 777.e1-777.e4.

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title = "Optimal efficacy of interferon-free HCV retreatment after protease inhibitor failure in real life",

abstract = "Objectives First-generation protease-inhibitors (PIs) have suboptimal efficacy in GT-1 patients with advanced liver disease, and patients experiencing treatment failure may require urgent retreatment. Our objective was to analyse 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-centre 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 three different strategies: A) with {\textquoteleft}GRT-guided{\textquoteright} regimens (N = 18); B) with {\textquoteleft}AASLD/EASL recommended, not GRT-guided{\textquoteright} regimens (N = 72); C) with {\textquoteleft}not recommended, not GRT-guided{\textquoteright} regimens (N = 31). Overall SVR rate was 91%, but all 18 patients treated with {\textquoteleft}GRT-guided{\textquoteright} regimens reached SVR (100%), despite heterogeneity in treatment duration, use of PI and ribavirin, versus 68/72 patients (94.4%) receiving {\textquoteleft}AASLD/EASL recommended, not GRT-guided{\textquoteright} regimens. SVR was strongly reduced (77.4%) among the 31 patients who received a {\textquoteleft}not recommended, not GRT-guided regimen{\textquoteright} (p <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; three out of four had a baseline R155K NS3-RAS. All seven patients treated with paritaprevir-containing regimens reached SVR, regardless of 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 PIs to be reconsidered when chosen after a RASs evaluation.",

keywords = "Cirrhosis, Direct acting antivirals, Genotypic resistance testing, HCV failure, HCV resistance, NS5A-inhibitors, Protease-inhibitors, Retreatment",

author = "V. Cento and S. Barbaliscia and I. Lenci and T. Ruggiero and Magni, {C. F.} and S. Paolucci and S. Babudieri and M. Siciliano and C. Pasquazzi and A. Ciancio and Perno, {C. F.} and F. Ceccherini-Silberstein and V. Micheli and Y. Troshina and E. Biliotti and M. Milana and M. Melis and E. Teti and L. Lambiase and B. Menzaghi and Nicolini, {L. A.} and S. Marenco and {Di Maio}, {V. C.} and M. Aragri and A. Pecchioli and A. Bertoli and C. Sarrecchia and M. Macera and N. Coppola and M. Puoti and D. Romagnoli and A. Pellicelli and S. Bonora and S. Novati and F. Baldanti and V. Ghisetti and M. Andreoni and G. Taliani and G. Rizzardini and M. Angelico and {on behalf of} and {the HCV retreatment team VIRONET-C study group}",

year = "2017",

month = oct,

day = "1",

doi = "10.1016/j.cmi.2017.04.005",

language = "English",

volume = "23",

pages = "777.e1--777.e4",

journal = "Clinical Microbiology and Infection",

issn = "1198-743X",

publisher = "Elsevier B.V.",

number = "10",

}

TY - JOUR

T1 - Optimal efficacy of interferon-free HCV retreatment after protease inhibitor failure in real life

AU - Cento, V.

AU - Barbaliscia, S.

AU - Lenci, I.

AU - Ruggiero, T.

AU - Magni, C. F.

AU - Paolucci, S.

AU - Babudieri, S.

AU - Siciliano, M.

AU - Pasquazzi, C.

AU - Ciancio, A.

AU - Perno, C. F.

AU - Ceccherini-Silberstein, F.

AU - Micheli, V.

AU - Troshina, Y.

AU - Biliotti, E.

AU - Milana, M.

AU - Melis, M.

AU - Teti, E.

AU - Lambiase, L.

AU - Menzaghi, B.

AU - Nicolini, L. A.

AU - Marenco, S.

AU - Di Maio, V. C.

AU - Aragri, M.

AU - Pecchioli, A.

AU - Bertoli, A.

AU - Sarrecchia, C.

AU - Macera, M.

AU - Coppola, N.

AU - Puoti, M.

AU - Romagnoli, D.

AU - Pellicelli, A.

AU - Bonora, S.

AU - Novati, S.

AU - Baldanti, F.

AU - Ghisetti, V.

AU - Andreoni, M.

AU - Taliani, G.

AU - Rizzardini, G.

AU - Angelico, M.

AU - on behalf of

AU - the HCV retreatment team VIRONET-C study group

PY - 2017/10/1

Y1 - 2017/10/1

N2 - Objectives First-generation protease-inhibitors (PIs) have suboptimal efficacy in GT-1 patients with advanced liver disease, and patients experiencing treatment failure may require urgent retreatment. Our objective was to analyse 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-centre 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 three 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, use of PI and ribavirin, versus 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 <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; three out of four had a baseline R155K NS3-RAS. All seven patients treated with paritaprevir-containing regimens reached SVR, regardless of 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 PIs to be reconsidered when chosen after a RASs evaluation.

AB - Objectives First-generation protease-inhibitors (PIs) have suboptimal efficacy in GT-1 patients with advanced liver disease, and patients experiencing treatment failure may require urgent retreatment. Our objective was to analyse 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-centre 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 three 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, use of PI and ribavirin, versus 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 <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; three out of four had a baseline R155K NS3-RAS. All seven patients treated with paritaprevir-containing regimens reached SVR, regardless of 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 PIs to be reconsidered when chosen after a RASs evaluation.

KW - Cirrhosis

KW - Direct acting antivirals

KW - Genotypic resistance testing

KW - HCV failure

KW - HCV resistance

KW - NS5A-inhibitors

KW - Protease-inhibitors

KW - Retreatment

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