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Efficacy and safety of glecaprevir and pibrentasvir treatment for 8 or 12 weeks in patients with recurrent hepatitis C after liver transplantation: a Japanese multicenter experience

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

Background

Efficacy of 8-week regimen with direct-acting antivirals (DAA) for patients with hepatitis C after liver transplantation has not been clarified. This study aimed to clarify the efficacy and safety of glecaprevir and pibrentasvir therapy for 8 and 12 weeks in Japanese patients with recurrent hepatitis C after liver transplantation.

Methods

A cohort study of liver transplant recipients with recurrent hepatitis C treated with glecaprevir (300 mg/day) and pibrentasvir (120 mg/day) was performed at nine liver transplant centers in Japan.

Results

Twenty-five patients with hepatitis C after liver transplantation were treated with glecaprevir and pibrentasvir. Twenty-four patients completed the treatment protocol; treatment was discontinued in one patient who had nausea at 3 days after the initiation of treatment. All the 24 patients who completed the 8- or 12-week treatment protocol achieved a sustained virological response 12 weeks after completion of treatment (SVR12). The SVR12 rates in patients with HCV genotype 1 and 2 were 100% (21 of 21 patients) and 75% (3 of 4 patients), respectively. All patients with prior DAA therapy failure (n = 6), jaundice (n = 4), and liver cirrhosis (n = 4) achieved SVR12. Seven of 8 patients (88%) with severe renal impairment achieved SVR12. Adverse events occurred in 6 of 25 patients (24%), including serious adverse events in 2 patients (8%). Treatment-related adverse events were nausea, pruritus, and mild renal dysfunction.

Conclusions

Eight- or 12-week regimen of glecaprevir and pibrentasvir is efficacious and safe in patients with recurrent HCV infection after liver transplantation, even in difficult-to-treat populations, including patients with severe renal impairment, prior DAA experience, liver cirrhosis, or jaundice after liver transplantation.

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Abbreviations

HCC:

Hepatocellular carcinoma

HCV:

Hepatitis C virus

LDLT:

Living donor liver transplantation

DAA:

Direct-acting antivirals

SVR:

Sustained virological response

PCR:

Polymerase chain reaction

ITT:

Intent-to-treat

eGFR:

Estimated glomerular filtration rate

References

  1. Liver transplantation in Japan. Registry by the Japanese Liver Transplantation Society. Jpn J Transplant. 2018;53:109–23.

    Google Scholar 

  2. Berenguer M, Ferrell L, Watson J, et al. HCV-related fibrosis progression following liver transplantation: increase in recent years. J Hepatol. 2000;32:673–84.

    Article  CAS  PubMed  Google Scholar 

  3. Terrault N. Liver transplantation in the setting of chronic HCV. Best Pract Res Clin Gastroenterol. 2012;26:531–48.

    Article  PubMed  Google Scholar 

  4. Ueda Y, Uemoto S. Interferon-free therapy for hepatitis C in liver transplant recipients. Transplantation. 2016;100:54–60.

    Article  CAS  PubMed  Google Scholar 

  5. HCV guidance: recommendations for testing, managing, and treating hepatitis C. Patients who develop recurrent HCV infection post liver transplantation. https://www.hcvguidelines.org/unique-populations/post-liver-transplant. Accessed 21 Sept 2017

  6. Belli LS, Duvoux C, Berenguer M, et al. ELITA consensus statements on the use of DAAs in liver transplant candidates and recipients. J Hepatol. 2017;67:585–602.

    Article  CAS  PubMed  Google Scholar 

  7. Ueda Y, Ikegami T, Akamatsu N, et al. Treatment with sofosbuvir and ledipasvir without ribavirin for 12 weeks is highly effective for recurrent hepatitis C virus genotype 1b infection after living donor liver transplantation: a Japanese multicenter experience. J Gastroenterol. 2017;52:986–91.

    Article  CAS  PubMed  Google Scholar 

  8. Reau N, Kwo PY, Rhee S, et al. Glecaprevir/pibrentasvir treatment in liver or kidney transplant patients with hepatitis c virus infection. Hepatology. 2018;68:1298–307.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Chayama K, Suzuki F, Karino Y, et al. Efficacy and safety of glecaprevir/pibrentasvir in Japanese patients with chronic genotype 1 hepatitis C virus infection with and without cirrhosis. J Gastroenterol. 2018;53:557–65.

    Article  PubMed  Google Scholar 

  10. Toyoda H, Chayama K, Suzuki F, et al. Efficacy and safety of glecaprevir/pibrentasvir in Japanese patients with chronic genotype 2 hepatitis C virus infection. Hepatology. 2018;67:505–13.

    Article  CAS  PubMed  Google Scholar 

  11. Ohno O, Mizokami M, Wu RR, et al. New hepatitis C virus (HCV) genotyping system that allows for identification of HCV genotypes 1a, 1b, 2a, 2b, 3a, 3b, 4, 5a, and 6a. J Clin Microbiol. 1997;35:201–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Asselah T, Kowdley KV, Zadeikis N, et al. Efficacy of glecaprevir/pibrentasvir for 8 or 12 weeks in patients with hepatitis C virus genotype 2, 4, 5, or 6 infection without cirrhosis. Clin Gastroenterol Hepatol. 2018;16:417–26.

    Article  CAS  PubMed  Google Scholar 

  13. Zeuzem S, Foster GR, Wang S, et al. Glecaprevir-pibrentasvir for 8 or 12 weeks in HCV genotype 1 or 3 infection. N Engl J Med. 2018;378:354–69.

    Article  CAS  PubMed  Google Scholar 

  14. Forns X, Lee SS, Valdes J, et al. Glecaprevir plus pibrentasvir for chronic hepatitis C virus genotype 1, 2, 4, 5, or 6 infection in adults with compensated cirrhosis (EXPEDITION-1): a single-arm, open-label, multicentre phase 3 trial. Lancet Infect Dis. 2017;17:1062–8.

    Article  CAS  PubMed  Google Scholar 

  15. Gane E, Lawitz E, Pugatch D, et al. Glecaprevir and pibrentasvir in patients with HCV and severe renal impairment. N Engl J Med. 2017;377:1448–55.

    Article  CAS  PubMed  Google Scholar 

  16. Kumada H, Watanabe T, Suzuki F, et al. Efficacy and safety of glecaprevir/pibrentasvir in HCV-infected Japanese patients with prior DAA experience, severe renal impairment, or genotype 3 infection. J Gastroenterol. 2018;53:566–75.

    Article  CAS  PubMed  Google Scholar 

  17. Poordad F, Felizarta F, Asatryan A, et al. Glecaprevir and pibrentasvir for 12 weeks for hepatitis C virus genotype 1 infection and prior direct-acting antiviral treatment. Hepatology. 2017;66:389–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Poordad F, Pol S, Asatryan A, et al. Glecaprevir/pibrentasvir in patients with hepatitis C virus genotype 1 or 4 and past direct-acting antiviral treatment failure. Hepatology. 2018;67:1253–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Charlton M, Everson GT, Flamm SL, et al. Ledipasvir and sofosbuvir plus ribavirin for treatment of HCV infection in patients with advanced liver disease. Gastroenterology. 2015;149:649–59.

    Article  CAS  Google Scholar 

  20. Ueda Y, Uemoto S. Decreased tacrolimus concentration following a temporal increase during interferon-free therapy with asunaprevir and daclatasvir in patients with recurrent hepatitis C after liver transplantation. Transpl Int. 2016;29:119–21.

    Article  PubMed  Google Scholar 

  21. Ikegami T, Ueda Y, Akamatsu N, et al. Asunaprevir and daclatasvir for recurrent hepatitis C after liver transplantation: A Japanese multicenter experience. Clin Transplant. 2017;31:e13109.

    Article  CAS  Google Scholar 

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Acknowledgements

This research is supported by the Research Program on Hepatitis from Japan Agency for Medical Research and development (Grant no. JP18fk0210023h0002), AMED.

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Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Yoshihide Ueda & Hiroshi Seno

  2. Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan

    Tsuyoshi Kobayashi

  3. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Toru Ikegami & Yoshihiko Maehara

  4. Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

    Satoshi Miuma

  5. Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University School of Medicine, Mie, Japan

    Shugo Mizuno

  6. Division of Artificial Organ and Transplantation, Department of Surgery, University of Tokyo, Tokyo, Japan

    Nobuhisa Akamatsu

  7. Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

    Akinobu Takaki

  8. Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Masatoshi Ishigami

  9. Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

    Mitsuhisa Takatsuki

  10. Department of Transplantation and Pediatric Surgery, Postgraduate School of Medical Science, Kumamoto University, Kumamoto, Japan

    Yasuhiko Sugawara

  11. Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Shinji Uemoto

Authors
  1. Yoshihide Ueda
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  2. Tsuyoshi Kobayashi
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  3. Toru Ikegami
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  4. Satoshi Miuma
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  5. Shugo Mizuno
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  6. Nobuhisa Akamatsu
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  7. Akinobu Takaki
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  8. Masatoshi Ishigami
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  9. Mitsuhisa Takatsuki
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  10. Yasuhiko Sugawara
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  11. Yoshihiko Maehara
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  12. Shinji Uemoto
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  13. Hiroshi Seno
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Corresponding author

Correspondence to Toru Ikegami.

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Ueda, Y., Kobayashi, T., Ikegami, T. et al. Efficacy and safety of glecaprevir and pibrentasvir treatment for 8 or 12 weeks in patients with recurrent hepatitis C after liver transplantation: a Japanese multicenter experience. J Gastroenterol 54, 660–666 (2019). https://doi.org/10.1007/s00535-019-01561-1

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  • DOI: https://doi.org/10.1007/s00535-019-01561-1

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