Goki Suda1, Norihiro Furusyo2, Hidenori Toyoda3, Yoshiiku Kawakami4, Hiroki Ikeda5, Michihiro Suzuki5, Keiko Arataki6, Nami Mori7, Keiji Tsuji7, Yoshio Katamura8, Koichi Takaguchi9, Toru Ishikawa10, Kunihiko Tsuji11, Noritomo Shimada12, Atsushi Hiraoka13, Sho Yamsaki2, Masato Nakai1, Takuya Sho1, Kenichi Morikawa1, Koji Ogawa1, Mineo Kudo14, Atsushi Nagasaka15, Ken Furuya16, Yoshiya Yamamoto17, Kanji Kato18, Yoshiyuki Ueno19, Etsuko Iio20, Yasuhito Tanaka20, Masayuki Kurosaki21, Takashi Kumada3, Kazuaki Chayama4, Naoya Sakamoto22. 1. Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan. 2. Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan. 3. Department of Gastroenterology, Ogaki Municipal Hospital, Gifu, Japan. 4. Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan. 5. Division of Gastroenterology and Hepatology, St. Marianna University School of Medicine, Kanagawa, Japan. 6. Tsuchiya General Hospital, Hiroshima, Japan. 7. Department of Gastroenterology/Liver Center, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital, Hiroshima, Japan. 8. Department of Gastroenterology, Onomichi General Hospital, Hiroshima, Japan. 9. Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan. 10. Department of Gastroenterology and Hepatology, Saiseikai Niigata Daini Hospital, Niigata, Japan. 11. Center for Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan. 12. Division of Gastroenterology and Hepatology, Ootakanomori Hospital, Chiba, Japan. 13. Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan. 14. Sapporo Hokuyu Hospital, Hokkaido, Japan. 15. Sapporo City General Hospital, Hokkaido, Japan. 16. Department of Gastroenterology and Hepatology, Japan Community Health Care Organization (JCHO) Hokkaido Hospital, Hokkaido, Japan. 17. Hakodate City Hospital, Hokkaido, Japan. 18. Iwamisawa Manicipal General Hospital, Hokkaido, Japan. 19. Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata, Japan. 20. Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. 21. Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan. 22. Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan. sakamoto@med.hokudai.ac.jp.
Abstract
BACKGROUND: Hepatitis C virus (HCV) infection is common in hemodialysis patients and worsens their prognosis, while antiviral therapy options are limited. Recently, clinical trial and real-world, small-scale studies have reported excellent responses to direct-acting antivirals in patients with advanced chronic kidney diseases. However, real-world, large-scale data were lacking. This large multicenter analysis included HCV-infected hemodialysis patients receiving combination therapy with a nonstructural protein 5A (NS5A) inhibitor, daclatasvir (DCV), and a protease inhibitor, asunaprevir (ASV). METHODS: Twenty-three centers in Japan participated in this study of 123 hemodialysis patients with genotype 1 HCV infection, who received DCV/ASV combination therapy between November 2014 and March 2016. We collected and analyzed data relating to treatment outcome, baseline clinical information, laboratory measurements (during and after the treatment), and adverse events. RESULTS: Thirty-nine patients (31.7%) had advanced liver fibrosis, 12 (9.8%) had histories of hepatocellular carcinoma (HCC), and 18 (14.6%) had baseline resistance-associated variants (RAVs) of NS5A. The overall sustained virological response (SVR)12 rate was 95.9% (118/123). Notably, all patients with HCC and 94.4% (17/18) of those with NS5A RAVs achieved SVR12. Significant factors associated with non-SVR were advanced fibrosis and the interleukin-28B non-TT genotype at rs8099917. Four patients (3.3%) discontinued therapy because of adverse events including elevated serum alanine transaminase levels (n = 2), rash (n = 1), and HCC (n = 1); all of these achieved SVR12. CONCLUSIONS: This real-world, nationwide study revealed that DCV/ASV combination therapy was safe and highly effective for hemodialysis patients with genotype 1 HCV infections. This study was registered at the UMIN Clinical Trials Registry (UMIN000024227).
BACKGROUND: Hepatitis C virus (HCV) infection is common in hemodialysis patients and worsens their prognosis, while antiviral therapy options are limited. Recently, clinical trial and real-world, small-scale studies have reported excellent responses to direct-acting antivirals in patients with advanced chronic kidney diseases. However, real-world, large-scale data were lacking. This large multicenter analysis included HCV-infected hemodialysis patients receiving combination therapy with a nonstructural protein 5A (NS5A) inhibitor, daclatasvir (DCV), and a protease inhibitor, asunaprevir (ASV). METHODS: Twenty-three centers in Japan participated in this study of 123 hemodialysis patients with genotype 1 HCV infection, who received DCV/ASV combination therapy between November 2014 and March 2016. We collected and analyzed data relating to treatment outcome, baseline clinical information, laboratory measurements (during and after the treatment), and adverse events. RESULTS: Thirty-nine patients (31.7%) had advanced liver fibrosis, 12 (9.8%) had histories of hepatocellular carcinoma (HCC), and 18 (14.6%) had baseline resistance-associated variants (RAVs) of NS5A. The overall sustained virological response (SVR)12 rate was 95.9% (118/123). Notably, all patients with HCC and 94.4% (17/18) of those with NS5A RAVs achieved SVR12. Significant factors associated with non-SVR were advanced fibrosis and the interleukin-28B non-TT genotype at rs8099917. Four patients (3.3%) discontinued therapy because of adverse events including elevated serum alanine transaminase levels (n = 2), rash (n = 1), and HCC (n = 1); all of these achieved SVR12. CONCLUSIONS: This real-world, nationwide study revealed that DCV/ASV combination therapy was safe and highly effective for hemodialysis patients with genotype 1 HCV infections. This study was registered at the UMIN Clinical Trials Registry (UMIN000024227).
Authors: P Mathurin; C Mouquet; T Poynard; C Sylla; H Benalia; C Fretz; V Thibault; J F Cadranel; B Bernard; P Opolon; P Coriat; M O Bitker Journal: Hepatology Date: 1999-01 Impact factor: 17.425
Authors: Paul J Pockros; K Rajender Reddy; Parvez S Mantry; Eric Cohen; Michael Bennett; Mark S Sulkowski; David E Bernstein; Daniel E Cohen; Nancy S Shulman; Deli Wang; Amit Khatri; Manal Abunimeh; Thomas Podsadecki; Eric Lawitz Journal: Gastroenterology Date: 2016-03-11 Impact factor: 22.682
Authors: Eric G Meissner; Dimitra Bon; Ludmila Prokunina-Olsson; Wei Tang; Henry Masur; Thomas R O'Brien; Eva Herrmann; Shyamasundaran Kottilil; Anuoluwapo Osinusi Journal: J Infect Dis Date: 2013-12-23 Impact factor: 5.226
Authors: Robert A Fridell; Chunfu Wang; Jin-Hua Sun; Donald R O'Boyle; Peter Nower; Lourdes Valera; Dike Qiu; Susan Roberts; Xin Huang; Bernadette Kienzle; Marc Bifano; Richard E Nettles; Min Gao Journal: Hepatology Date: 2011-12 Impact factor: 17.425