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Daclatasvir and asunaprevir in hemodialysis patients with hepatitis C virus infection: a nationwide retrospective study in Japan

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
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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).

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Abbreviations

ASV:

Asunaprevir

CHC:

Chronic hepatitis C

DAAs:

Direct-acting antivirals

DCV:

Daclatasvir

DM:

Diabetes mellitus

ESRD:

End-stage renal disease

HCV:

Hepatitis C virus

HD:

Hemodialysis

RAVs:

Resistance-associated variants

SVR:

Sustained virological response

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Acknowledgements

The authors would like to thank all of the patients and their families, as well as the investigators and staff of the 23 participating institutions.

Author information

Author notes

  1. Goki Suda, Norihiro Furusyo, Hidenori Toyoda, and Yoshiiku Kawakami contributed equally to this work.

Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan

    Goki Suda, Masato Nakai, Takuya Sho, Kenichi Morikawa, Koji Ogawa & Naoya Sakamoto

  2. Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan

    Norihiro Furusyo & Sho Yamsaki

  3. Department of Gastroenterology, Ogaki Municipal Hospital, Gifu, Japan

    Hidenori Toyoda & Takashi Kumada

  4. Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan

    Yoshiiku Kawakami & Kazuaki Chayama

  5. Division of Gastroenterology and Hepatology, St. Marianna University School of Medicine, Kanagawa, Japan

    Hiroki Ikeda & Michihiro Suzuki

  6. Tsuchiya General Hospital, Hiroshima, Japan

    Keiko Arataki

  7. Department of Gastroenterology/Liver Center, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital, Hiroshima, Japan

    Nami Mori & Keiji Tsuji

  8. Department of Gastroenterology, Onomichi General Hospital, Hiroshima, Japan

    Yoshio Katamura

  9. Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan

    Koichi Takaguchi

  10. Department of Gastroenterology and Hepatology, Saiseikai Niigata Daini Hospital, Niigata, Japan

    Toru Ishikawa

  11. Center for Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan

    Kunihiko Tsuji

  12. Division of Gastroenterology and Hepatology, Ootakanomori Hospital, Chiba, Japan

    Noritomo Shimada

  13. Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan

    Atsushi Hiraoka

  14. Sapporo Hokuyu Hospital, Hokkaido, Japan

    Mineo Kudo

  15. Sapporo City General Hospital, Hokkaido, Japan

    Atsushi Nagasaka

  16. Department of Gastroenterology and Hepatology, Japan Community Health Care Organization (JCHO) Hokkaido Hospital, Hokkaido, Japan

    Ken Furuya

  17. Hakodate City Hospital, Hokkaido, Japan

    Yoshiya Yamamoto

  18. Iwamisawa Manicipal General Hospital, Hokkaido, Japan

    Kanji Kato

  19. Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata, Japan

    Yoshiyuki Ueno

  20. Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

    Etsuko Iio & Yasuhito Tanaka

  21. Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan

    Masayuki Kurosaki

Authors
  1. Goki Suda
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  2. Norihiro Furusyo
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  3. Hidenori Toyoda
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  4. Yoshiiku Kawakami
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  5. Hiroki Ikeda
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  6. Michihiro Suzuki
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  7. Keiko Arataki
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  8. Nami Mori
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  9. Keiji Tsuji
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  10. Yoshio Katamura
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  11. Koichi Takaguchi
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  12. Toru Ishikawa
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  13. Kunihiko Tsuji
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  14. Noritomo Shimada
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  15. Atsushi Hiraoka
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  16. Sho Yamsaki
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  17. Masato Nakai
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  18. Takuya Sho
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  19. Kenichi Morikawa
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  20. Koji Ogawa
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  21. Mineo Kudo
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  22. Atsushi Nagasaka
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  23. Ken Furuya
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  24. Yoshiya Yamamoto
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  25. Kanji Kato
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  26. Yoshiyuki Ueno
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  28. Yasuhito Tanaka
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  29. Masayuki Kurosaki
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  30. Takashi Kumada
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  31. Kazuaki Chayama
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  32. Naoya Sakamoto
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Contributions

GS, NF, HT, YK designed the study, and wrote the initial draft of the manuscript. NS contributed to analysis and interpretation of data, and assisted in the preparation of the manuscript. All other authors have contributed to data collection and interpretation, and critically reviewed the manuscript. The final version of the manuscript was approved by all authors.

Corresponding author

Correspondence to Naoya Sakamoto.

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Conflict of interest

N. Sakamoto 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. G. Suda received research grants from Bristol Myers Squibb. K. Chayama has received research grants and consulting fees from Bristol-Myers Squibb, Dainippon Sumitomo Pharma, Mitsubishi Tanabe Pharma, Daiichi Sankyo, Toray Industries, Otsuka Pharmaceutical Company, and GlaxoSmithKline K.K. Y. Ueno has received research grants from Bristol-Myers Squibb, MSD K.K., Gilead Sciences, Inc., and AbbVie G.K. K. Furuya has received lecture fees from Bristol-Myers Squibb and MSD K.K. H. Toyoda and T. Kumada received research grants from Bristol Myers Squibb. K. Takaguchi has received lecture fees from Bristol-Myers Squibb. Y. Tanaka have received lecture fees from Bristol-Myers Squibb, MSD K.K., Chugai Pharmaceutical Co., Ltd., AbbVie Inc., Janssen Pharmaceutical K.K., Gilead Sciences, and a research grant from Bristol-Myers Squibb, Chugai Pharmaceutical Co., Ltd,, and AbbVie Inc. The other authors have nothing to disclose.

Funding

This study was supported in part by grants from the Japan Agency for Medical Research and Development.

Electronic supplementary material

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535_2017_1353_MOESM1_ESM.tif

Correlation between the FIB4 index and FibroScan value. The correlation between the baseline FIB4 index and FibroScan value was analyzed by Pearson’s rank test (n = 68). (TIFF 5199 kb)

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Suda, G., Furusyo, N., Toyoda, H. et al. Daclatasvir and asunaprevir in hemodialysis patients with hepatitis C virus infection: a nationwide retrospective study in Japan. J Gastroenterol 53, 119–128 (2018). https://doi.org/10.1007/s00535-017-1353-y

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  • DOI: https://doi.org/10.1007/s00535-017-1353-y

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