Hidenori Toyoda1, Masanori Atsukawa2, Koichi Takaguchi3, Tomonori Senoh3, Kojiro Michitaka4, Atsushi Hiraoka4, Shinichi Fujioka5, Chisa Kondo2, Tomomi Okubo6, Haruki Uojima7, Toshifumi Tada8, Hirohito Yoneyama9, Tsunamasa Watanabe10, Toru Asano11, Toru Ishikawa12, Hideyuki Tamai13, Hiroshi Abe14, Keizo Kato14, Kunihiko Tsuji15, Chikara Ogawa16, Noritomo Shimada17, Etsuko Iio18, Akihiro Deguchi19, Ei Itobayashi20, Shigeru Mikami21, Akio Moriya22, Hironao Okubo23, Joji Tani24, Akihito Tsubota25, Yasuhito Tanaka18, Tsutomu Masaki9, Katsuhiko Iwakiri2, Takashi Kumada8. 1. Department of Gastroenterology, Ogaki Municipal Hospital, 4-86 Minaminokawa, Ogaki, Gifu, 503-8502, Japan. hmtoyoda@spice.ocn.ne.jp. 2. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan. 3. Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan. 4. Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan. 5. Department of Gastroenterology, Okayama Saiseikai General Hospital, Okayama, Japan. 6. Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan. 7. Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Sagamihara, Japan. 8. Department of Gastroenterology, Ogaki Municipal Hospital, 4-86 Minaminokawa, Ogaki, Gifu, 503-8502, Japan. 9. Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kida, Japan. 10. Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan. 11. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokyo Metropolitan Bokutoh Hospital, Tokyo, Japan. 12. Department of Hepatology, Saiseikai Niigata Daini Hospital, Niigata, Japan. 13. Department of Hepatology, Wakayama Rosai Hospital, Wakayama, Japan. 14. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Shinmatusdo Central General Hospital, Matsudo, Japan. 15. Center of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan. 16. Department of Gastroenterology and Hepatology, Takamatsu Red Cross Hospital, Takamatsu, Japan. 17. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Otakanomori Hospital, Kashiwa, Japan. 18. Department of Virology and Liver Unit, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan. 19. Department of Gastroenterology, Kagawa Rosai Hospital, Marugame, Japan. 20. Department of Gastroenterology, Asahi General Hospital, Asahi, Japan. 21. Division of Gastroenterology, Department of Internal Medicine, Kikkoman General Hospital, Noda, Japan. 22. Department of Gastroenterology, Mitoyo General Hospital, Kannonji, Japan. 23. Department of Gastroenterology, Juntendo University Nerima Hospital, Tokyo, Japan. 24. Department of Internal Medicine, Yashima General Hospital, Takamatsu, Japan. 25. Core Research Facilities for Basic Science, The Jikei University School of Medicine, Tokyo, Japan.
Abstract
BACKGROUND: The real-world virological efficacy and safety of an interferon (IFN)-free direct-acting antiviral (DAA) therapy with elbasvir (EBR) and grazoprevir (GZR) were evaluated in Japanese patients chronically infected with hepatitis C virus (HCV) genotype 1. METHODS: The rate of sustained virologic response (SVR) and safety were analyzed in patients who started the EBR/GZR regimen between November 2016 and July 2017. SVR rates were compared based on patient baseline characteristics. RESULTS: Overall, 371 of 381 patients (97.4%) achieved SVR. Multivariate analysis identified a history of failure to IFN-free DAA therapy and the presence of double resistance-associated substitutions (RASs) in HCV non-structural protein 5A (NS5A) as factors significantly associated with failure to EBR/GZR treatment. The SVR rates of patients with a history of IFN-free DAA therapy and those with double RASs were 55.6 and 63.6%, respectively. In all other subpopulations, the SVR rates were more than 90%. There were no severe adverse events associated with the treatment. CONCLUSIONS: The EBR/GZR regimen yielded high virological efficacy with acceptable safety. Patients with a history of failure to IFN-free DAA therapy or with double RASs in HCV-NS5A remained difficult to treat with this regimen.
BACKGROUND: The real-world virological efficacy and safety of an interferon (IFN)-free direct-acting antiviral (DAA) therapy with elbasvir (EBR) and grazoprevir (GZR) were evaluated in Japanese patients chronically infected with hepatitis C virus (HCV) genotype 1. METHODS: The rate of sustained virologic response (SVR) and safety were analyzed in patients who started the EBR/GZR regimen between November 2016 and July 2017. SVR rates were compared based on patient baseline characteristics. RESULTS: Overall, 371 of 381 patients (97.4%) achieved SVR. Multivariate analysis identified a history of failure to IFN-free DAA therapy and the presence of double resistance-associated substitutions (RASs) in HCV non-structural protein 5A (NS5A) as factors significantly associated with failure to EBR/GZR treatment. The SVR rates of patients with a history of IFN-free DAA therapy and those with double RASs were 55.6 and 63.6%, respectively. In all other subpopulations, the SVR rates were more than 90%. There were no severe adverse events associated with the treatment. CONCLUSIONS: The EBR/GZR regimen yielded high virological efficacy with acceptable safety. Patients with a history of failure to IFN-free DAA therapy or with double RASs in HCV-NS5A remained difficult to treat with this regimen.
Authors: P Marcellin; N Boyer; A Gervais; M Martinot; M Pouteau; C Castelnau; A Kilani; J Areias; A Auperin; J P Benhamou; C Degott; S Erlinger Journal: Ann Intern Med Date: 1997-11-15 Impact factor: 25.391
Authors: Y Kawakami; M Imamura; H Ikeda; M Suzuki; K Arataki; M Moriishi; N Mori; K Kokoroishi; Y Katamura; T Ezaki; T Ueno; K Ide; T Masaki; H Ohdan; K Chayama Journal: J Viral Hepat Date: 2016-06-27 Impact factor: 3.728
Authors: Adriaan J van der Meer; Bart J Veldt; Jordan J Feld; Heiner Wedemeyer; Jean-François Dufour; Frank Lammert; Andres Duarte-Rojo; E Jenny Heathcote; Michael P Manns; Lorenz Kuske; Stefan Zeuzem; W Peter Hofmann; Robert J de Knegt; Bettina E Hansen; Harry L A Janssen Journal: JAMA Date: 2012-12-26 Impact factor: 56.272
Authors: Y Imai; S Kawata; S Tamura; I Yabuuchi; S Noda; M Inada; Y Maeda; Y Shirai; T Fukuzaki; I Kaji; H Ishikawa; Y Matsuda; M Nishikawa; K Seki; Y Matsuzawa Journal: Ann Intern Med Date: 1998-07-15 Impact factor: 25.391