Koichi Takaguchi1, Hidenori Toyoda2, Akemi Tsutsui3, Yoshiyuki Suzuki4, Makoto Nakamuta5, Michio Imamura6, Tomonori Senoh3, Takuya Nagano3, Toshifumi Tada2, Yoshihiko Tachi7, Atsushi Hiraoka8, Kojiro Michitaka8, Hiroshi Shibata9, Kouji Joko10, Hironao Okubo11, Kunihiko Tsuji12, Shintaro Takaki13, Tsunamasa Watanabe14, Chikara Ogawa15, Kazuaki Chayama6, Takashi Kumada2, Masatoshi Kudo16, Hiromitsu Kumada4. 1. Department of Hepatology, Kagawa Prefectural Central Hospital, 1-2-1 Asahi-machi, Takamatsu, Kagawa, 760-8557, Japan. k.takaguchi@chp-kagawa.jp. 2. Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan. 3. Department of Hepatology, Kagawa Prefectural Central Hospital, 1-2-1 Asahi-machi, Takamatsu, Kagawa, 760-8557, Japan. 4. Department of Hepatology, Toranomon Hospital, Tokyo, Japan. 5. National Hospital Organization, Kyushu Medical Center, Fukuoka, Japan. 6. Department of Gastroenterology and Metabolism, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan. 7. Department of Gastroenterology, Komaki City Hospital, Komaki, Japan. 8. Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan. 9. Department of Gastroenterology, Tokushima Prefectural Central Hospital, Tokushima, Japan. 10. Center for Liver-Biliary-Pancreatic Disease, Matsuyama Red Cross Hospital, Matsuyama, Japan. 11. Department of Gastroenterology, Juntendo University Nerima Hospital, Tokyo, Japan. 12. Center of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan. 13. Department of Gastroenterology, Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital, Hiroshima, Japan. 14. Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan. 15. Department of Gastroenterology and Hepatology, Takamatsu Red Cross Hospital, Takamatsu, Japan. 16. Department of Gastroenterology and Hepatology, Kinki University School of Medicine, Osaka, Japan.
Abstract
BACKGROUND: The virological efficacy and safety of the direct-acting antiviral (DAA) regimen consisting of daclatasvir, asunaprevir, and beclabuvir (DCV/ASV/BCV) for patients chronically infected with hepatitis C virus (HCV) genotype 1 have not been previously evaluated in Japanese real-world settings. METHODS: In a Japanese nationwide multicenter study, the rate of sustained virologic response (SVR) and safety were analyzed in 91 patients who started the DCV/ASV/BCV regimen between November 2016 and July 2017. SVR rates were compared based on baseline patient characteristics. RESULTS: More than 60% of patients had a history of failure to achieve SVR with interferon (IFN)-free DAA therapy. Overall, 50 of 91 patients (54.9%) achieved SVR. Multivariate analysis identified a history of failure with IFN-free DAA therapy and pretreatment HCV RNA levels as factors significantly associated with treatment failure. Whereas the SVR rate in patients without a history of IFN-free DAA therapy was 91.7% (33 of 36 patients), it was only 30.9% (17 of 55 patients) among patients with a history of IFN-free DAA therapy. The rate of discontinuation due to an adverse event was 4.4%. CONCLUSIONS: Many patients treated with the DCV/ASV/BCV regimen have a history of a failure to achieve SVR with previous IFN-free DAA therapy. SVR rate was not as high as that in pre-approval clinical trial of this regimen in IFN-free DAA-naïve patients. In addition, most patients with a history of failure with IFN-free DAA therapy, particularly the DCV/ASV regimen, showed resistance to this regimen.
BACKGROUND: The virological efficacy and safety of the direct-acting antiviral (DAA) regimen consisting of daclatasvir, asunaprevir, and beclabuvir (DCV/ASV/BCV) for patientschronically infected with hepatitis C virus (HCV) genotype 1 have not been previously evaluated in Japanese real-world settings. METHODS: In a Japanese nationwide multicenter study, the rate of sustained virologic response (SVR) and safety were analyzed in 91 patients who started the DCV/ASV/BCV regimen between November 2016 and July 2017. SVR rates were compared based on baseline patient characteristics. RESULTS: More than 60% of patients had a history of failure to achieve SVR with interferon (IFN)-free DAA therapy. Overall, 50 of 91 patients (54.9%) achieved SVR. Multivariate analysis identified a history of failure with IFN-free DAA therapy and pretreatment HCV RNA levels as factors significantly associated with treatment failure. Whereas the SVR rate in patients without a history of IFN-free DAA therapy was 91.7% (33 of 36 patients), it was only 30.9% (17 of 55 patients) among patients with a history of IFN-free DAA therapy. The rate of discontinuation due to an adverse event was 4.4%. CONCLUSIONS: Many patients treated with the DCV/ASV/BCV regimen have a history of a failure to achieve SVR with previous IFN-free DAA therapy. SVR rate was not as high as that in pre-approval clinical trial of this regimen in IFN-free DAA-naïve patients. In addition, most patients with a history of failure with IFN-free DAA therapy, particularly the DCV/ASV regimen, showed resistance to this regimen.
Authors: Richard K Sterling; Eduardo Lissen; Nathan Clumeck; Ricard Sola; Mendes Cassia Correa; Julio Montaner; Mark S Sulkowski; Francesca J Torriani; Doug T Dieterich; David L Thomas; Diethelm Messinger; Mark Nelson Journal: Hepatology Date: 2006-06 Impact factor: 17.425
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Authors: Andrew J Muir; Fred Poordad; Jacob Lalezari; Gregory Everson; Gregory J Dore; Robert Herring; Aasim Sheikh; Paul Kwo; Christophe Hézode; Paul J Pockros; Albert Tran; Joseph Yozviak; Nancy Reau; Alnoor Ramji; Katherine Stuart; Alexander J Thompson; John Vierling; Bradley Freilich; James Cooper; Wayne Ghesquiere; Rong Yang; Fiona McPhee; Eric A Hughes; E Scott Swenson; Philip D Yin Journal: JAMA Date: 2015-05-05 Impact factor: 56.272
Authors: Gregory T Everson; Karen D Sims; Maribel Rodriguez-Torres; Christophe Hézode; Eric Lawitz; Marc Bourlière; Veronique Loustaud-Ratti; Vinod Rustgi; Howard Schwartz; Harvey Tatum; Patrick Marcellin; Stanislas Pol; Paul J Thuluvath; Timothy Eley; Xiaodong Wang; Shu-Pang Huang; Fiona McPhee; Megan Wind-Rotolo; Ellen Chung; Claudio Pasquinelli; Dennis M Grasela; David F Gardiner Journal: Gastroenterology Date: 2013-10-30 Impact factor: 22.682