Skip to main content
SpringerLink
Log in

Three patients treated with sofosbuvir plus ledipasvir for recurrent hepatitis C after liver transplantation

  • Case Report
  • Published:
Clinical Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

We previously reported results of interferon (IFN)-free daclatasvir and asunaprevir for the treatment of recurrent hepatitis C virus (HCV) genotype 1 infection after liver transplantation (LT). Here we report three patients who achieved viral response with no effect on the blood concentrations of immunosuppressive agents following sofosbuvir plus ledipasvir treatment. The first patient was a 68-year-old female with HCV-related liver cirrhosis who failed to respond to pegylated-IFN and ribavirin (PEG-IFN/RBV) after living donor LT. She had been treated with 50 mg/day of cyclosporine. The second was a 63-year-old male with HCV-related liver cirrhosis and hepatocellular carcinoma who failed to respond to PEG-IFN/RBV after living donor LT. He had been treated with 50 mg/day of cyclosporine. The third was a 63-year-old female with HCV-related liver cirrhosis. She had been treated with tacrolimus. High alanine aminotransferase levels persisted after LT. Liver biopsy examination revealed active hepatitis or chronic rejection. Therefore, sofosbuvir plus ledipasvir therapy was started. However, the combination treatment was stopped at 4 weeks due to development of interstitial pneumonia. Serum HCV RNA became negative at the time treatment was discontinued and remained negative 12 weeks after cessation of therapy in all three cases. Sofosbuvir plus ledipasvir treatment showed a remarkable viral response with little effect on blood levels of immunosuppressive agents for recurrent HCV genotype 1 infection after LT.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. 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 

  2. Forman LM, Lewis JD, Berlin JA, Feldman HI, Lucey MR. The association between hepatitis C infection and survival after orthotopic liver transplantation. Gastroenterology. 2002;122:889–96.

    Article  PubMed  Google Scholar 

  3. Crespo G, Marino Z, Navasa M, Forns X. Viral hepatitis in liver transplantation. Gastroenterology. 2012;142(1373–83):e1.

    Google Scholar 

  4. Berenguer M, Palau A, Aguilera V, Rayon JM, Juan FS, Prieto M. Clinical benefits of antiviral therapy in patients with recurrent hepatitis C following liver transplantation. Am J Transplant. 2008;8:679–87.

    Article  CAS  PubMed  Google Scholar 

  5. Schmidt SC, Bahra M, Bayraktar S, et al. Antiviral treatment of patients with recurrent hepatitis C after liver transplantation with pegylated interferon. Dig Dis Sci. 2010;55:2063–9.

    Article  CAS  PubMed  Google Scholar 

  6. 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  PubMed  Google Scholar 

  7. Kwo PY, Mantry PS, Coakley E, et al. An interferon-free antiviral regimen for HCV after liver transplantation. N Engl J Med. 2014;18(371):2375–82.

    Article  Google Scholar 

  8. Pellicelli AM, Montalbano M, Lionetti R, et al. Sofosbuvir plus daclatasvir for post-transplant recurrent hepatitis C: potent antiviral activity but no clinical benefit if treatment is given late. Dig Liver Dis. 2014;46:923–7.

    Article  CAS  PubMed  Google Scholar 

  9. Kumada H, Suzuki Y, Ikeda K, et al. Daclatasvir plus asunaprevir for chronic HCV genotype 1b infection. Hepatology. 2014;59:2083–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Kawaoka T, Imamura M, Morio K, et al. Three patients treated with daclatasvir and asunaprevir for recurrent hepatitis C after liver transplantation: case report. Hepatol Res. 2016;46:707–12.

    Article  CAS  PubMed  Google Scholar 

  11. Mizokami M, Yokosuka O, Takehara T, 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;15:645–53.

    Article  CAS  PubMed  Google Scholar 

  12. Kwok RM, Ahn J, Schiano TD, et al. Sofosbuvir plus ledispasvir for recurrent hepatitis C in liver transplant recipients. Liver transplant. 2016;22:1536–43.

    Article  Google Scholar 

  13. Omichi K, Akamatsu N, Mori K, et al. Asunaprevir/daclatasvir and sofosbuvir/ledipasvir for recurrent hepatitis C following living donor liver transplantation. Hepatol Res. 2016. doi:10.1111/hepr.12845.

  14. Yoshimi S, Ochi H, Murakami E, et al. Rapid, sensitive, and accurate evaluation of drug resistant mutant (NS5A-Y93H) strain frequency in genotype 1b HCV by invader assay. PLoS One. 2015;10:e0130022.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Morio R, Imamura M, Kawakami Y, et al. Safety and efficacy of dual therapy with daclatasvir and asunaprevir for older patients with chronic hepatitis C. J gastroenterol. 2016. doi: 10.1007/s00535-016-1255-4.

  16. Gumber SC, Chopra S. Hepatitis C: a multifaceted disease. Review of extrahepatic manifestations. Ann Intern Med. 1995;15(123):615–20.

    Article  Google Scholar 

  17. Misiani R, Bellavita P, Fenili D, et al. Interferon alfa-2a therapy in cryoglobulinemia associated with hepatitis C virus. N Engl J Med. 1994;17(330):751–6.

    Article  Google Scholar 

  18. Tsuge M, Hiramatsu A, Shinohara F, et al. Improvement of renal dysfunction in a patient with hepatitis C virus-related liver cirrhosis by daclatasvir and asunaprevir combination therapy: a case report. Hepatol Res. 2016;46:944–8.

    Article  PubMed  Google Scholar 

  19. Narang TK, Ahrens W, Russo MW. Post-liver transplant cholestatic hepatitis C: a systematic review of clinical and pathological findings and application of consensus criteria. Liver transplant. 2010;16:1228–35.

    Article  Google Scholar 

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

    Article  PubMed  Google Scholar 

  21. Ueda Y, Kaido T, Hatano E, Ohtsuru S, Uemoto S. Safe and effective treatment with daclatasvir and asunaprevir in a liver transplant recipient with severe cholestatic hepatitis C. Hepatol Res. 2015;45:1360–2.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan

    Tomokazu Kawaoka, Michio Imamura, Kei Morio, Yuki Nakamura, Masataka Tsuge, Clair Nelson Hayes, Yoshiiku Kawakami, Hiroshi Aikata & Kazuaki Chayama

  2. Laboratory for Digestive Diseases, Center for Genomic Medicine, RIKEN, Hiroshima, Japan

    Hidenori Ochi & Kazuaki Chayama

  3. Programs for Biomedical Research, Division of Frontier Medical Science, Department of Surgery, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan

    Kouhei Ishiyama & Hideki Ohdan

Authors
  1. Tomokazu Kawaoka
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michio Imamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kei Morio
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yuki Nakamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Masataka Tsuge
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Clair Nelson Hayes
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yoshiiku Kawakami
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hiroshi Aikata
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hidenori Ochi
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Kouhei Ishiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Hideki Ohdan
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Kazuaki Chayama
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michio Imamura.

Ethics declarations

Conflict of interest

Kazuaki Chayama received honoraria from MSD K.K.,Bristol-Meyers Squibb and research funding from Abbvie, Dainippon Sumitomo Pharma, The Institute of Physical and Chemical Research (RIKEN). Michio Imamura received research funding from Bristol-Meyers Squibb. Masataka Tsuge received research funding from Bristol-Meyers Squibb. The other authors declare no conflict of interest.

Human rights

All procedures followed have been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Informed consent

None.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 52 kb)

Supplementary material 2 (PDF 46 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kawaoka, T., Imamura, M., Morio, K. et al. Three patients treated with sofosbuvir plus ledipasvir for recurrent hepatitis C after liver transplantation. Clin J Gastroenterol 10, 179–184 (2017). https://doi.org/10.1007/s12328-017-0722-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12328-017-0722-7

Keywords

Search

Navigation