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Journal of Gastroenterology

, Volume 54, Issue 1, pp 78–86 | Cite as

Safety and efficacy of elbasvir and grazoprevir in Japanese hemodialysis patients with genotype 1b hepatitis C virus infection

  • Goki Suda
  • Masayuki Kurosaki
  • Jun Itakura
  • Namiki Izumi
  • Yoshihito Uchida
  • Satoshi Mochida
  • Chitomi Hasebe
  • Masami Abe
  • Hiroaki Haga
  • Yoshiyuki Ueno
  • Ikuto Masakane
  • Kazumichi Abe
  • Atsushi Takahashi
  • Hiromasa Ohira
  • Ken Furuya
  • Masaru Baba
  • Yoshiya Yamamoto
  • Tomoe Kobayashi
  • Atsuhiko Kawakami
  • Kenichi Kumagai
  • Katsumi Terasita
  • Masatsugu Ohara
  • Naoki Kawagishi
  • Machiko Umemura
  • Masato Nakai
  • Takuya Sho
  • Mitsuteru Natsuizaka
  • Kenichi Morikawa
  • Koji Ogawa
  • Naoya SakamotoEmail author
  • for the NORTE Study Group
Original Article—Liver, Pancreas, and Biliary Tract

Abstract

Background

The prevalence of hepatitis C virus (HCV) infection in hemodialysis patients is high and results in a poor prognosis. Thus, safer and more effective treatment regimens are required. In this prospective multicenter study, we investigated the efficacy and safety of the novel HCV-NS5A-inhibitor, elbasvir, and protease inhibitor, grazoprevir in Japanese hemodialysis patients with genotype 1b HCV infection.

Methods

This study is registered at the UMIN Clinical Trials Registry as UMIN00002578. A total of 23 Japanese dialysis patients with genotype 1b HCV infection who were treated with elbasvir and grazoprevir between January 2017 and March 2018 and followed for more than 12 weeks after treatment completion were included. We evaluated the sustained virologic response at 12 weeks after treatment completion (SVR12) and safety during treatment.

Results

Of the 23 patients, 7 had advanced liver fibrosis and 2 had a signature resistance-associated variant of NS5A (NS5A RAVs)-L31M/V or Y93H at baseline. All patients completed therapy, and 96.7% (22/23) of the patients achieved SVR12. All patients with advanced liver fibrosis and signature NS5A RAVs at baseline achieved SVR12 with a high safety profile. No patient experienced lethal or severe adverse events during therapy, and the most common adverse event was anemia. One patient, who was a non-responder to this therapy, had a history of failure with daclatasvir and asunaprevir therapies and had NS5A RAVs of A92K at baseline, but not signature NS5A RAVs.

Conclusions

Grazoprevir and elbasvir combination is highly effective and safe for hemodialysis patients with genotype 1b HCV infection.

Keywords

HCV Hemodialysis Elbasvir Grazoprevir 

Abbreviations

DAAs

Direct-acting antivirals

HCV

Hepatitis C virus

CHC

Chronic hepatitis C

HD

Hemodialysis

SVR

Sustained virological response

DCV

Daclatasvir

ASV

Asunaprevir

DM

Diabetes mellitus

RAVs

Resistance-associated variants

GZR

Grazoprevir

Notes

Acknowledgements

The authors would like to thank all patients and their families as well as the investigators and staff of the participating institutions, NORTE study group and Yamagata CKD meeting. The principal investigators of the NORTE study sites are listed below: Junichi Yoshida (JCHO Sapporo Hokushin Hospital), Atsushi Nagasaka (Sapporo City General Hospital), Akira Fuzinaga (Abashiri-Kosei General Hospital), Hideaki Kikuchi, Tomofumi Atarashi (Obihiro-Kosei General Hospital), Ken Furuya (JCHO Hokkaido Hospital), Shuichi Muto (National Hospital Organization Hokkaido Medical Center), Takashi Meguro (Hokkaido Gastroenterology Hospital), Akiyoshi Saga (Kaisei Hospital), Munenori Okamoto (Aiiku Hospital), Masaki Katagiri (Sapporo Hokuyu Hospital), Takuto Miyagishima (Kushiro Rosai Hospital), Jun Konno (Hakodate Central General Hospital), Kenichi Kumagai (Mori city National Health Insurance Hospital), Manabu Onodera (NTT EAST Sapporo Hospital), Tomoe Kobayashi (Tomakomai City Hospital), Minoru Uebayashi (Japanese Red Cross Kitami Hospital), Kanji Katou (Iwamizawa Municipal General Hospital), Yasuyuki Kunieda (Wakkanai City Hospital), Miki Tateyama (Tomakomai Nissho Hospital), Atsuhiko Kawakami (Sapporo Century Hospital), Izumi Tsunematsu (Touei hospital), Keisuke Shinada (Keiwakai Ebetsu Hospital) and Yoshiya Ymamoto (Hakodate City General Hospital).

Funding

This study was supported in part by grants from Merck & Co., and was supported by the Japan Agency for Medical Research and Development (AMED) Grant: JP18fk0210018h0002 and JSPS KAKENHI (Grant number 16K09334).

Compliance with ethical standards

Conflict of interest

Professor Naoya Sakamoto has received lecture fees from Bristol Myers Squibb, and Pharmaceutical K. K., grants and endowments from MSD, K. K. and Chugai Pharmaceutical Co., Ltd., and a research grant from Gilead Sciences Inc and AbbVie GK. Dr. Goki Suda has received research grants from Merck & Co and Bristol Myers Squibb. Dr. Masayuki Kurosaki received lecture fee from Abbvie GK and Gilead Sciences. Dr. Yoshihito Uchida has received research grant from AbbVie GK. Professor Satoshi Mochida has received speaking fees or honoraria from AbbVie GK, Ajinomoto Pharmaceuticals Co. Ltd., Bristol Myers Squibb Co., Gilead Sciences Inc., MSD K. K., Sumitomo Dainippon Pharma Co., Toray Medical Co. Ltd., has received research grants from A2 Healthcare Co., AbbVie GK, Bristol Myers Squibb Co., Chugai Pharmaceutical Co. Ltd., EA Pharma Co. Ltd., Mitsubishi Tanabe Pharma Co., MSD K. K., Sumitomo Dainippon Pharma Co., Toray Medical Co. Ltd., has received patent royalties from SRL Inc. Dr. Hiroaki Haga has received grants and endowments from Gilead Sciences. Professor Yoshiyuki Ueno has received grants and endowments from Gilead Sciences, MSD K. K., and AbbVie GK. Dr Ikuto Masakane has received lecture fee from Bristol Myers Squibb and AbbVie GK. The other authors have no conflicts of interest to disclose.

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Copyright information

© Japanese Society of Gastroenterology 2018

Authors and Affiliations

  • Goki Suda
    • 1
  • Masayuki Kurosaki
    • 2
  • Jun Itakura
    • 2
  • Namiki Izumi
    • 2
  • Yoshihito Uchida
    • 3
  • Satoshi Mochida
    • 3
  • Chitomi Hasebe
    • 4
  • Masami Abe
    • 4
  • Hiroaki Haga
    • 5
  • Yoshiyuki Ueno
    • 5
  • Ikuto Masakane
    • 6
  • Kazumichi Abe
    • 7
  • Atsushi Takahashi
    • 7
  • Hiromasa Ohira
    • 7
  • Ken Furuya
    • 8
  • Masaru Baba
    • 8
  • Yoshiya Yamamoto
    • 9
  • Tomoe Kobayashi
    • 10
  • Atsuhiko Kawakami
    • 11
  • Kenichi Kumagai
    • 12
  • Katsumi Terasita
    • 1
  • Masatsugu Ohara
    • 1
  • Naoki Kawagishi
    • 1
  • Machiko Umemura
    • 1
  • Masato Nakai
    • 1
  • Takuya Sho
    • 1
  • Mitsuteru Natsuizaka
    • 1
  • Kenichi Morikawa
    • 1
  • Koji Ogawa
    • 1
  • Naoya Sakamoto
    • 1
    Email author
  • for the NORTE Study Group
  1. 1.Department of Gastroenterology and Hepatology, Graduate School of MedicineHokkaido UniversitySapporoJapan
  2. 2.Department of Gastroenterology and HepatologyMusashino Red Cross HospitalMusashinoJapan
  3. 3.Department of Gastroenterology and Hepatology, Faculty of MedicineSaitama Medical UniversitySaitamaJapan
  4. 4.Department of GastroenterologyJapanese Red Cross Asahikawa HospitalAsahikawaJapan
  5. 5.Department of Gastroenterology, Faculty of MedicineYamagata UniversityYamagataJapan
  6. 6.Yabuki HospitalYamagataJapan
  7. 7.Department of GastroenterologyFukushima Medical University School of MedicineFukushimaJapan
  8. 8.Department of Gastroenterology and HepatologyJapan Community Health Care Organization (JCHO) Hokkaido HospitalSapporoJapan
  9. 9.Hakodate City HospitalHakodateJapan
  10. 10.Tomakomai City HospitalTomakomaiJapan
  11. 11.Century HospitalSapporoJapan
  12. 12.Mori City National Health Insurance HospitalMoriJapan

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