Skip to main content
Log in

Safety and efficacy of dual direct-acting antiviral therapy (daclatasvir and asunaprevir) for chronic hepatitis C virus genotype 1 infection in patients on hemodialysis

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

An Erratum to this article was published on 07 March 2016

Abstract

Background

Hepatitis C virus (HCV) infection is a major comorbidity in patients receiving hemodialysis. Interferon-based antiviral therapy to eradicate HCV is less effective in patients receiving hemodialysis than patients without renal dysfunction. Recently reported combination therapy with two oral direct-acting antiviral drugs, daclatasvir and asunaprevir, both of which are metabolized in the liver and excreted into the bile ducts, reportedly showed a high rate of HCV eradication. We evaluated the safety and efficacy of this therapy in patients receiving hemodialysis.

Methods

The safety and viral responses were compared among patients infected with HCV genotype 1, between 28 patients receiving hemodialysis, and propensity score-matched 56 patients without renal dysfunction.

Results

The reduction in serum HCV RNA levels 1 day after the start of therapy was significantly larger (p = 0.0329) and the disappearance of serum HCV RNA occurred significantly earlier (p = 0.0017) in patients receiving hemodialysis than those without renal dysfunction. The rates of sustained virologic response, i.e., the eradication of HCV, were comparable between two groups; the rate of SVR12 was 100 % in patients receiving hemodialysis and 94.6 % in patients without renal dysfunction. No adverse constitutional events were observed in either of the groups. The elevation of serum alanine aminotransferase levels, a known adverse effect of these drugs, was observed in comparable rate of patients between the two groups.

Conclusions

The therapy with daclatasvir and asunaprevir has high antiviral efficacy in patients receiving hemodialysis with a comparable safety profile to patients without renal dysfunction.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Berenguer M. Treatment of chronic hepatitis C in hemodialysis patients. Hepatology. 2008;48(5):1690–9.

    Article  CAS  PubMed  Google Scholar 

  2. Fabrizi F, Poordad FF, Martin P. Hepatitis C infection and the patient with end-stage renal disease. Hepatology. 2002;36(1):3–10.

    Article  PubMed  Google Scholar 

  3. Martin P, Fabrizi F. Hepatitis C virus and kidney disease. J Hepatol. 2008;49(4):613–24.

    Article  CAS  PubMed  Google Scholar 

  4. Liu CH, Kao JH. Treatment of hepatitis C virus infection in patients with end-stage renal disease. J Gastroenterol Hepatol. 2011;26(2):228–39.

    Article  CAS  PubMed  Google Scholar 

  5. Stehman-Breen CO, Emerson S, Gretch D, et al. Risk of death among chronic dialysis patients infected with hepatitis C virus. Am J Kidney Dis. 1998;32(4):629–34.

    Article  CAS  PubMed  Google Scholar 

  6. Pereira BJ, Natov SN, Bouthot BA, et al. Effects of hepatitis C infection and renal transplantation on survival in end-stage renal disease. Kidney Int. 1998;53(5):1374–81.

    Article  CAS  PubMed  Google Scholar 

  7. Espinosa M, Martin-Malo A, Alvarez de Lara MA, et al. Risk of death and liver cirrhosis in anti-HCV positive long-term hemodialysis patients. Nephrol Dial Transplant. 2001;16(8):1669–74.

    Article  CAS  PubMed  Google Scholar 

  8. 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.

    CAS  PubMed  Google Scholar 

  9. Lok AS, Gardiner DF, Lawitz E, et al. Preliminary study of two antiviral agents for hepatitis C genotype 1. N Engl J Med. 2012;366(3):216–24.

    Article  CAS  PubMed  Google Scholar 

  10. Chayama K, Takahashi S, Toyota J, et al. Dual therapy with the nonstructural protein 5A inhibitor, daclatasvir, and the nonstructural protein 3 protease inhibitor, asunaprevir, in hepatitis C virus genotype 1b-infected null responders. Hepatology. 2012;55(3):724–8.

    Article  Google Scholar 

  11. Kumada H, Suzuki Y, Ikeda K, et al. Daclatasvir plus asunaprevir for chronic HCV genotype 1 infection. Hepatology. 2014;59(6):2083–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Garimella T, Wang R, Luo WL, et al. Single-dose pharmacokinetics and safety of daclatasvir in subject with renal function impairment. Antivir Ther. 2015;20(5):535–43.

    Article  PubMed  Google Scholar 

  13. Garimella T, He B, Luo WL, et al. Asunaprevir pharmacokinetics and safety in subjects with impaired renal function. Hepatology. 2013;58(10):430A.

    Google Scholar 

  14. 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(1):201–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Uchida Y, Kouyama J, Naiki K, Mochida S. A novel simple assay system to quantify the percent HCV RNA levels of NS5A Y93H mutant strains and Y93 wild-type strains relative to the total HCV-RNA levels to determine the indication for antiviral therapy with NS5A inhibitors. PLoS One. 2014;9(11):e112647.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Lopes EPA, Gouveia EC, Albuquerque ACC, et al. Determination of the cut-off of serum alanine aminotransferase in patients undergoing hemodialysis, to identify biochemical activity in patients with hepatitis C viremia. J Clin Virol. 2006;35(3):298–302.

    Article  CAS  PubMed  Google Scholar 

  17. Matsuo S, Imai E, Horio M, et al. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis. 2009;53(6):982–92.

    Article  CAS  PubMed  Google Scholar 

  18. Guh JY, Lai YH, Yang CY, et al. Impact of decreased serum transaminase levels on the evaluation of viral hepatitis patients. Nephron. 1995;69(4):459–65.

    Article  CAS  PubMed  Google Scholar 

  19. Yuki N, Ishida H, Inoue T, et al. Reappraisal of biochemical hepatitis C activity in hemodialysis patients. J Clin Gastroenterol. 2000;30(2):187–94.

    Article  CAS  PubMed  Google Scholar 

  20. Liu CH, Huang CF, Liu CJ, et al. Pegylated interferon-α2a with or without low-dose ribavirin for treatment-naïve patients with hepatitis C virus genotype 1 receiving hemodialysis. A randomized trial. Ann Intern Med. 2013;159(11):729–38.

    Article  PubMed  Google Scholar 

  21. Deltenre P, Moreno C, Tran A, et al. Anti-viral therapy in haemodialysed HCV patients: efficacy, tolerance and treatment strategy. Alim Pharmacol Ther. 2011;34(4):454–61.

    Article  CAS  Google Scholar 

  22. Toyoda H, Kumada T, Kiriyama S, et al. An early viral response to standard interferon-alpha identifies resistance to combination therapy with peginterferon and ribavirin in patients infected by HCV genotype 1. J Med Virol. 2010;82(9):1537–44.

    Article  CAS  PubMed  Google Scholar 

  23. Toyoda H, Kumada T, Tada T, et al. Association between HCV amino acid substitutions and outcome of peginterferon and ribavirin combination therapy in HCV genotype 1b and high viral load. J Gastroenterol Hepatol. 2010;25(6):1072–8.

    Article  CAS  PubMed  Google Scholar 

  24. Fujiwra K, Kaneko S, Kakumu S, et al. Double filtration plasmapheresis and interferon combination therapy for chronic hepatitis C patients with genotype 1 and high viral load. Hepatol Res. 2007;37(9):701–10.

    Article  Google Scholar 

  25. Kaneko S, Sata M, Ide T, et al. Efficacy and safety of double filtration plasmapheresis in combination with interferon therapy for chronic hepatitis C. Hepatol Res. 2010;40(11):1072–81.

    Article  CAS  PubMed  Google Scholar 

  26. Fabrizi F, Dulai G, Dixit V, Bunnapradist S, Martin P. Meta-analysis: interferon for the treatment of chronic hepatitis C in dialysis patients. Aliment Pharmacol Ther. 2003;18(11–12):1071–81.

    Article  CAS  PubMed  Google Scholar 

  27. Russo MW, Goldsweig CD, Jacobson IM, Brown RS Jr. Interferon monotherapy for dialysis patients with chronic hepatitis C: an analysis of the literature on efficacy and safety. Am J Gastroenterol. 2003;98(7):1610–5.

    Article  CAS  PubMed  Google Scholar 

  28. Singal AG, Volk ML, Jensen D, Di Bisceglie AM, Schoenfeld PS. A sustained viral response is associated with reduced liver-related morbidity and mortality in patients with hepatitis C virus. Clin Gastroenterol Hepatol. 2010;8:280–8.

    Article  PubMed  Google Scholar 

  29. Ikeda K, Saitoh S, Arase Y, et al. Effect of interferon therapy on hepatocellular carcinogenesis in patients with chronic hepatitis type C: a long-term observation study of 1643 patients using statistical bias correction with proportional hazard analysis. Hepatology. 1999;29:1124–30.

    Article  CAS  PubMed  Google Scholar 

  30. Imai Y, Kawata S, Tamura S, et al. Relation of interferon therapy and hepatocellular carcinoma in patients with chronic hepatitis C. Ann Intern Med. 1998;129:94–9.

    Article  CAS  PubMed  Google Scholar 

  31. Yoshida H, Shiratori Y, Moriyama M, et al. Interferon therapy reduces the risk for hepatocellular carcinoma: national surveillance program of cirrhotic and noncirrhotic patients with chronic hepatitis C in Japan. Ann Intern Med. 1999;131:174–81.

    Article  CAS  PubMed  Google Scholar 

  32. Kasahara A, Hayashi N, Mochizuki K, et al. Risk factors for hepatocellular carcinoma and its incidence after interferon treatment in patients with chronic hepatitis C. Hepatology. 1998;27:1394–402.

    Article  CAS  PubMed  Google Scholar 

  33. Ogawa E, Furusyo N, Kajiwara E, et al. Efficacy of pegylated interferon alpha-2b and ribavirin treatment on the risk of hepatocellular carcinoma of patients with chronic hepatitis C: a prospective multicenter study. J Hepatol. 2013;58:495–501.

    Article  CAS  PubMed  Google Scholar 

  34. van der Meer AJ, Veldt BJ, Feld JJ, et al. Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis. JAMA. 2012;308:2584–93.

    Article  PubMed  Google Scholar 

  35. Lee MH, Yang HI, Lu SN, et al. Chronic hepatitis C virus infection increases mortality from hepatic and extrahepatic diseases: a community-based long-term prospective study. J Infect Dis. 2012;206:469–77.

    Article  PubMed  Google Scholar 

  36. Tada T, Kumada T, Toyoda H, et al. Viral eradication reduces all-cause mortality in patients with chronic hepatitis C virus infection: a propensity score analysis. Liver Int (in press).

  37. Tanaka J, Katayama K, Matsuo J, et al. The association of hepatitis C virus infection with the prognosis of chronic hemodialysis patients: a retrospective study of 3,064 patients between 1999 and 2010. J Med Virol. 2015;87:1558–64.

    Article  CAS  Google Scholar 

  38. Roth D, Nelson DR, Bruchefeld A, et al. Grazoprevir plus elbasvir in treatment-naïve and treatment-experienced patients with hepatitis C virus genotype 1 infection and stage 4–5 chronic kidney disease (the C-SURFER study): a combination phase 3 study. Lancet 2015;386(10):1537–45.

    Article  CAS  PubMed  Google Scholar 

  39. Pockros PJ, Reddy KR, Mantry PS, et al. Safety of ombitasvir/paritaprevir/ritonavir plus dasabuvir for treating HCVGT1 infection in patients with severe renal impairment or end-stage renal disease: the RUBY-1 study. J Hepatol. 2015;62(Suppl 1):S1145A.

    Google Scholar 

Download references

Acknowledgments

The authors thank Dr. Shintaro Ogawa, Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Science, for his technical assistance.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hidenori Toyoda.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Toyoda, H., Kumada, T., Tada, T. et al. Safety and efficacy of dual direct-acting antiviral therapy (daclatasvir and asunaprevir) for chronic hepatitis C virus genotype 1 infection in patients on hemodialysis. J Gastroenterol 51, 741–747 (2016). https://doi.org/10.1007/s00535-016-1174-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00535-016-1174-4

Keywords

Navigation