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Journal of Gastroenterology

, Volume 51, Issue 7, pp 733–740 | Cite as

Efficacy and safety of daclatasvir and asunaprevir combination therapy in chronic hemodialysis patients with chronic hepatitis C

  • Goki Suda
  • Mineo Kudo
  • Atsushi Nagasaka
  • Ken Furuya
  • Yoshiya Yamamoto
  • Tomoe Kobayashi
  • Keisuke Shinada
  • Miki Tateyama
  • Jun Konno
  • Yoko Tsukuda
  • Kazushi Yamasaki
  • Megumi Kimura
  • Machiko Umemura
  • Takaaki Izumi
  • Seiji Tsunematsu
  • Fumiyuki Sato
  • Katsumi Terashita
  • Masato Nakai
  • Hiromasa Horimoto
  • Takuya Sho
  • Mitsuteru Natsuizaka
  • Kenichi Morikawa
  • Koji Ogawa
  • Naoya Sakamoto
Original Article—Liver, Pancreas, and Biliary Tract

Abstract

Background

HCV infection in chronic hemodialysis patients is high, has a poor prognosis and high risk of renal graft failure, and requires nosocomial infection control measures. However, options of anti-HCV therapy in such patients are limited and unsatisfactory. In this study, we report effectiveness and safety of HCV-NS5A-inhibitor daclatasvir (DCV) and protease-inhibitor asunaprevir (ASV) combination therapy for hemodialysis patients with HCV infection.

Methods

This study was registered at the UMIN Clinical Trials Registry as UMIN000016355. Thirty-four dialysis patients were treated with DCV/ASV combination therapy between January 2015 and November 2015. Of those, 21 patients who were followed more than 12 weeks after treatment ended were included. We evaluated the 12-week sustained virologic response (SVR12) and adverse events during treatment.

Results

Of the 21 patients, four had compensated liver cirrhosis and three had resistance-associated variant of NS5A (NS5A RAVs)-Y93H at baseline. Overall, total of 95.5 % (20/21) of the patients achieved SVR12. Of note, all patients with cirrhosis or NS5A RAVs achieved SVR12. One relapser patient at 4 weeks post-treatment had NS3 D168E RAVs at baseline. A total of 20 patients (95.5 %) completed the 24-week therapy. One patient discontinued treatment at week 12 due to ALT elevations and achieved SVR12.

Conclusions

DAV and ASV combination therapy for chronic hemodialysis patients with HCV infection was highly effective and well tolerated, even in elderly patients and patients with liver cirrhosis and NS5A-RAVs.

Keywords

HCV Hemodialysis Daclatasvir Asunaprevir 

Abbreviations

DAAs

Direct-acting antivirals

HCV

Hepatitis C virus

CHC

Chronic hepatitis C

HD

Hemodialysis

RBV

Ribavirin

SVR

Sustained virological response

DCV

Daclatasvir

ASV

Asunaprevir

DM

Diabetes mellitus

RAVs

Resistance-associated variants

Notes

Acknowledgments

The authors would like to thank all patients and their families as well as the investigators and staff of the 21 participating institutions. 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, Manabu Onodera (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 (Aiiku Hospital), Mineo Kudou (Sapporo Hokuyu Hospital), Takuto Miyagishima (Kushiro Rosai Hospital), Jun Konno (Hakodate Central General Hospital), Kenichi Kumagai (Hakodate Medical Association Hospital), Nobuaki Akakura (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), Munenori Okamoto (Sapporo Century Hospital), Izumi Tsunematsu (Touei hospital), Keisuke Shinada (Keiwakai Ebetsu Hospital) and Yoshiya Ymamoto (Hakodate City General Hospital).

Financial disclosure

This study was supported in part by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan, the Japan Society for the Promotion of Science, the Japan Agency for Medical Research and Development and the Ministry of Health, Labour and Welfare of Japan.

Compliance with ethical standards

Conflict of interest

Professor Naoya 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 research grant from Gilead Sciences. Inc. Dr Goki Suda received research grants from Bristol Myers Squibb. The other authors have nothing to disclose.

References

  1. 1.
    Mohd Hanafiah K, Groeger J, Flaxman AD, Wiersma ST. Global epidemiology of hepatitis C virus infection: new estimates of age-specific antibody to HCV seroprevalence. Hepatology. 2013;57(4):1333–42.CrossRefPubMedGoogle Scholar
  2. 2.
    Seeff LB. Natural history of chronic hepatitis C. Hepatology. 2002;36(5 Suppl 1):S35–46.CrossRefPubMedGoogle Scholar
  3. 3.
    Iwasa Y, Otsubo S, Sugi O, Sato K, Asamiya Y, Eguchi A, et al. Patterns in the prevalence of hepatitis C virus infection at the start of hemodialysis in Japan. Clin Exp Nephrol. 2008;12(1):53–7.CrossRefPubMedGoogle Scholar
  4. 4.
    Bergman S, Accortt N, Turner A, Glaze J. Hepatitis C infection is acquired pre-ESRD. Am J Kidney Dis. 2005;45(4):684–9.CrossRefPubMedGoogle Scholar
  5. 5.
    Kalantar-Zadeh K, Kilpatrick RD, McAllister CJ, Miller LG, Daar ES, Gjertson DW, et al. Hepatitis C virus and death risk in hemodialysis patients. J Am Soc Nephrol. 2007;18(5):1584–93.CrossRefPubMedGoogle Scholar
  6. 6.
    Nakayama E, Akiba T, Marumo F, Sato C. Prognosis of anti-hepatitis C virus antibody-positive patients on regular hemodialysis therapy. J Am Soc Nephrol. 2000;11(10):1896–902.PubMedGoogle Scholar
  7. 7.
    Goodkin DA, Bragg-Gresham JL, Koenig KG, Wolfe RA, Akiba T, Andreucci VE, et al. Association of comorbid conditions and mortality in hemodialysis patients in Europe, Japan, and the United States: the Dialysis Outcomes and Practice Patterns Study (DOPPS). J Am Soc Nephrol. 2003;14(12):3270–7.CrossRefPubMedGoogle Scholar
  8. 8.
    Fabrizi F, Takkouche B, Lunghi G, Dixit V, Messa P, Martin P. The impact of hepatitis C virus infection on survival in dialysis patients: meta-analysis of observational studies. J Viral Hepat. 2007;14(10):697–703.PubMedGoogle Scholar
  9. 9.
    Akiba T, Hora K, Imawari M, Sato C, Tanaka E, Izumi N, et al. 2011 Japanese Society for Dialysis Therapy guidelines for the treatment of hepatitis C virus infection in dialysis patients. Ther Apher Dial. 2012;16(4):289–310.CrossRefPubMedGoogle Scholar
  10. 10.
    Kidney Disease: Improving Global O. KDIGO clinical practice guidelines for the prevention, diagnosis, evaluation, and treatment of hepatitis C in chronic kidney disease. Kidney Int Suppl. 2008;73(109):S1–S99.Google Scholar
  11. 11.
    Sakamoto N, Nakagawa M, Tanaka Y, Sekine-Osajima Y, Ueyama M, Kurosaki M, et al. Association of IL28B variants with response to pegylated-interferon alpha plus ribavirin combination therapy reveals intersubgenotypic differences between genotypes 2a and 2b. J Med Virol. 2011;83(5):871–8.CrossRefPubMedGoogle Scholar
  12. 12.
    Mizokami M, Yokosuka O, Takehara T, Sakamoto N, Korenaga M, Mochizuki H, et al. Ledipasvir and sofosbuvir fixed-dose combination with and without ribavirin for 12 weeks in treatment-naive and previously treated Japanese patients with genotype 1 hepatitis C: an open-label, randomised, phase 3 trial. Lancet Infect Dis. 2015;15(6):645–53.CrossRefPubMedGoogle Scholar
  13. 13.
    Omata M, Nishiguchi S, Ueno Y, Mochizuki H, Izumi N, Ikeda F, et al. Sofosbuvir plus ribavirin in Japanese patients with chronic genotype 2 HCV infection: an open-label, phase 3 trial. J Viral Hepat. 2014;21(11):762–8.CrossRefPubMedGoogle Scholar
  14. 14.
    Kumada H, Hayashi N, Izumi N, Okanoue T, Tsubouchi H, Yatsuhashi H, et al. Simeprevir (TMC435) once daily with peginterferon-alpha-2b and ribavirin in patients with genotype 1 hepatitis C virus infection: the CONCERTO-4 study. Hepatol Res. 2015;45(5):501–13.CrossRefPubMedGoogle Scholar
  15. 15.
    Hezode C, Forestier N, Dusheiko G, Ferenci P, Pol S, Goeser T, et al. Telaprevir and peginterferon with or without ribavirin for chronic HCV infection. N Engl J Med. 2009;360(18):1839–50.CrossRefPubMedGoogle Scholar
  16. 16.
    Fabrizi F, Dixit V, Messa P, Martin P. Interferon monotherapy of chronic hepatitis C in dialysis patients: meta-analysis of clinical trials. J Viral Hepat. 2008;15(2):79–88.PubMedGoogle Scholar
  17. 17.
    Gordon CE, Uhlig K, Lau J, Schmid CH, Levey AS, Wong JB. Interferon treatment in hemodialysis patients with chronic hepatitis C virus infection: a systematic review of the literature and meta-analysis of treatment efficacy and harms. Am J Kidney Dis. 2008;51(2):263–77.CrossRefPubMedGoogle Scholar
  18. 18.
    Ayaz C, Celen MK, Yuce UN, Geyik MF. Efficacy and safety of pegylated-interferon alpha-2a in hemodialysis patients with chronic hepatitis C. World J Gastroenterol. 2008;14(2):255–9.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Kumada H, Suzuki Y, Ikeda K, Toyota J, Karino Y, Chayama K, et al. Daclatasvir plus asunaprevir for chronic HCV genotype 1b infection. Hepatology. 2014;59(6):2083–91.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Vallet-Pichard A, Mallet V, Nalpas B, Verkarre V, Nalpas A, Dhalluin-Venier V, et al. FIB-4: an inexpensive and accurate marker of fibrosis in HCV infection. Comparison with liver biopsy and fibrotest. Hepatology. 2007;46(1):32–6.CrossRefPubMedGoogle Scholar
  21. 21.
    Guh JY, Lai YH, Yang CY, Chen SC, Chuang WL, Hsu TC, et al. Impact of decreased serum transaminase levels on the evaluation of viral hepatitis in hemodialysis patients. Nephron. 1995;69(4):459–65.CrossRefPubMedGoogle Scholar
  22. 22.
    Mathurin P, Mouquet C, Poynard T, Sylla C, Benalia H, Fretz C, et al. Impact of hepatitis B and C virus on kidney transplantation outcome. Hepatology. 1999;29(1):257–63.CrossRefPubMedGoogle Scholar
  23. 23.
    Company B-MS. Daklinza Tablets (daclatasvir) Japanese Prescribing Information 2014. 2014.Google Scholar
  24. 24.
    Company B-MS. Sunvepra Capsules (asunaprevir) Japanese Prescribing Information. 2014.Google Scholar
  25. 25.
    Suzuki F, Sezaki H, Akuta N, Suzuki Y, Seko Y, Kawamura Y, et al. Prevalence of hepatitis C virus variants resistant to NS3 protease inhibitors or the NS5A inhibitor (BMS-790052) in hepatitis patients with genotype 1b. J Clin Virol. 2012;54(4):352–4.CrossRefPubMedGoogle Scholar
  26. 26.
    Ono K, Ono T, Matsumata T. The pathogenesis of decreased aspartate aminotransferase and alanine aminotransferase activity in the plasma of hemodialysis patients: the role of vitamin B6 deficiency. Clin Nephrol. 1995;43(6):405–8.PubMedGoogle Scholar
  27. 27.
    Espinosa M, Martin-Malo A, Alvarez de Lara MA, Soriano S, Aljama P. High ALT levels predict viremia in anti-HCV-positive HD patients if a modified normal range of ALT is applied. Clin Nephrol. 2000;54(2):151–6.PubMedGoogle Scholar
  28. 28.
    Asahina Y, Tsuchiya K, Nishimura T, Muraoka M, Suzuki Y, Tamaki N, et al. alpha-fetoprotein levels after interferon therapy and risk of hepatocarcinogenesis in chronic hepatitis C. Hepatology. 2013;58(4):1253–62.CrossRefPubMedGoogle Scholar

Copyright information

© Japanese Society of Gastroenterology 2016

Authors and Affiliations

  • Goki Suda
    • 1
  • Mineo Kudo
    • 2
  • Atsushi Nagasaka
    • 3
  • Ken Furuya
    • 4
  • Yoshiya Yamamoto
    • 5
  • Tomoe Kobayashi
    • 6
  • Keisuke Shinada
    • 7
  • Miki Tateyama
    • 8
  • Jun Konno
    • 9
  • Yoko Tsukuda
    • 1
    • 3
  • Kazushi Yamasaki
    • 1
  • Megumi Kimura
    • 1
  • Machiko Umemura
    • 1
  • Takaaki Izumi
    • 1
  • Seiji Tsunematsu
    • 1
  • Fumiyuki Sato
    • 1
  • Katsumi Terashita
    • 1
  • Masato Nakai
    • 1
  • Hiromasa Horimoto
    • 1
    • 5
  • Takuya Sho
    • 1
  • Mitsuteru Natsuizaka
    • 1
  • Kenichi Morikawa
    • 1
  • Koji Ogawa
    • 1
  • Naoya Sakamoto
    • 1
  1. 1.Department of Gastroenterology and HepatologyGraduate School of Medicine, Hokkaido UniversitySapporoJapan
  2. 2.Sapporo Hokuyu HospitalHokkaidoJapan
  3. 3.Sapporo City General HospitalHokkaidoJapan
  4. 4.JCHO Hokkaido HospitalHokkaidoJapan
  5. 5.Hakodate City HospitalHokkaidoJapan
  6. 6.Tomakomai City HospitalHokkaidoJapan
  7. 7.Keiwakai Ebetsu HospitalHokkaidoJapan
  8. 8.Tomakomai Nissho HospitalHokkaidoJapan
  9. 9.Hakodate Central General HospitalHokkaidoJapan

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