BACKGROUND: Glecaprevir and pibrentasvir (GLE/PIB) are potent antiviral agents for hepatitis C virus (HCV) pan-genotypic infections; however, their clinical effectiveness and safety remain limited in the real-world. This study aimed to evaluate viral responses and the safety of GLE/PIB for patients with chronic HCV-1/2/3 infections during both initial- (Arm A) and re-treatment (Arm B) with all-oral direct-acting antiviral agents (DAAs). METHODS: This prospective-observational cohort study included Japanese patients with chronic HCV-1/2/3 infections (n = 271: 183 in Arm A and 83 in Arm B), who had started receiving GLE/PIB. Primary end point was a sustained virological response (SVR) rate at week 12 (SVR12) after the end of GLE/PIB treatment (EOT). RESULTS: SVR12 was achieved by 99.4% of patients (180/181: modified intention-to-treat (mITT) analysis excluding 2 patients lost to follow-up) in Arm A. One patient with an HCV-3b infection who discontinued at week 8 failed to achieve SVR12. SVR12 was achieved by 97.7% of patients (85/87: mITT excluding 1 patient lost to follow-up) in Arm B. Virological relapse occurred in 2 patients with HCV-1b, presenting common 5 loci of resistance-associated substitutions (RASs) including A92 RASs in the NS5A lesion at baseline. Any adverse events (AEs) (grade ≥ 3) occurred in 8 patients (3.0%). 8 patients (3.0%) discontinued due to AEs, however, all of them achieved SVR12. CONCLUSIONS: Initial and re-treatment with GLE/PIB are effective and safe for Japanese patients with HCV-1/2/3 in real-life settings. Further studies are required to elucidate the mechanism underlying treatment failures of GLE/PIB to completely eradicate HCV worldwide.
BACKGROUND:Glecaprevir and pibrentasvir (GLE/PIB) are potent antiviral agents for hepatitis C virus (HCV) pan-genotypic infections; however, their clinical effectiveness and safety remain limited in the real-world. This study aimed to evaluate viral responses and the safety of GLE/PIB for patients with chronic HCV-1/2/3infections during both initial- (Arm A) and re-treatment (Arm B) with all-oral direct-acting antiviral agents (DAAs). METHODS: This prospective-observational cohort study included Japanese patients with chronic HCV-1/2/3infections (n = 271: 183 in Arm A and 83 in Arm B), who had started receiving GLE/PIB. Primary end point was a sustained virological response (SVR) rate at week 12 (SVR12) after the end of GLE/PIB treatment (EOT). RESULTS: SVR12 was achieved by 99.4% of patients (180/181: modified intention-to-treat (mITT) analysis excluding 2 patients lost to follow-up) in Arm A. One patient with an HCV-3b infection who discontinued at week 8 failed to achieve SVR12. SVR12 was achieved by 97.7% of patients (85/87: mITT excluding 1 patient lost to follow-up) in Arm B. Virological relapse occurred in 2 patients with HCV-1b, presenting common 5 loci of resistance-associated substitutions (RASs) including A92 RASs in the NS5A lesion at baseline. Any adverse events (AEs) (grade ≥ 3) occurred in 8 patients (3.0%). 8 patients (3.0%) discontinued due to AEs, however, all of them achieved SVR12. CONCLUSIONS: Initial and re-treatment with GLE/PIB are effective and safe for Japanese patients with HCV-1/2/3 in real-life settings. Further studies are required to elucidate the mechanism underlying treatment failures of GLE/PIB to completely eradicate HCV worldwide.
Authors: Stefan Zeuzem; Graham R Foster; Stanley Wang; Armen Asatryan; Edward Gane; Jordan J Feld; Tarik Asselah; Marc Bourlière; Peter J Ruane; Heiner Wedemeyer; Stanislas Pol; Robert Flisiak; Fred Poordad; Wan-Long Chuang; Catherine A Stedman; Steven Flamm; Paul Kwo; Gregory J Dore; Gladys Sepulveda-Arzola; Stuart K Roberts; Ruth Soto-Malave; Kelly Kaita; Massimo Puoti; John Vierling; Edward Tam; Hugo E Vargas; Rafi Bruck; Francisco Fuster; Seung-Woon Paik; Franco Felizarta; Jens Kort; Bo Fu; Ran Liu; Teresa I Ng; Tami Pilot-Matias; Chih-Wei Lin; Roger Trinh; Federico J Mensa Journal: N Engl J Med Date: 2018-01-25 Impact factor: 91.245
Authors: Norah A Terrault; Stefan Zeuzem; Adrian M Di Bisceglie; Joseph K Lim; Paul J Pockros; Lynn M Frazier; Alexander Kuo; Anna S Lok; Mitchell L Shiffman; Ziv Ben Ari; Lucy Akushevich; Monika Vainorius; Mark S Sulkowski; Michael W Fried; David R Nelson Journal: Gastroenterology Date: 2016-08-24 Impact factor: 22.682
Authors: Marc Bourlière; Stuart C Gordon; Eugene R Schiff; Tram T Tran; Natarajan Ravendhran; Charles S Landis; Robert H Hyland; Luisa M Stamm; Jie Zhang; Hadas Dvory-Sobol; G Mani Subramanian; Diana M Brainard; John G McHutchison; Lawrence Serfaty; Alex J Thompson; Thomas E Sepe; Michael P Curry; K Rajender Reddy; Michael P Manns Journal: Lancet Gastroenterol Hepatol Date: 2018-05-31
Authors: David B Ascher; Jerome Wielens; Tracy L Nero; Larissa Doughty; Craig J Morton; Michael W Parker Journal: Sci Rep Date: 2014-04-23 Impact factor: 4.379