Advertisement

Treatment of Chronic Hepatitis C with the First-Generation Protease Inhibitor Telaprevir: Its Efficacy and Resistance Mutations

  • Yoshiyasu KarinoEmail author
Chapter

Abstract

Telaprevir, a first-generation protease inhibitor, was approved in 2011 for use in antiviral therapy for hepatitis C in combination with PEG-IFN and ribavirin, and treatment of hepatitis C entered a new stage. In the Japanese phase III trial, triple therapy with telaprevir/PEG-IFN/ribavirin showed a much higher sustained viral response (SVR) rate (73 %) than PEG-IFN and ribavirin combination alone (49.2 %) in treatment-naïve patients. Furthermore, in clinical practice more than 90 % of treatment-naïve patients achieved SVR by management of drug dosing. In most cases, telaprevir-resistant variants appeared at the time of the treatment failure. But most telaprevir-resistant strains were replaced by wild-type HCV in the natural course. Now, in the era of IFN-free therapy, the role of TVR has decreased, but TVR played a key pioneering role in the shift to direct-acting antiviral (DAA) therapy.

Keywords

Telaprevir Triple therapy Resistance mutation 

References

  1. 1.
    Lin K, Perni RB, Kwong AD, Lin C. VX-950, a novel hepatitis C virus (HCV) NS3-4A protease inhibitor, exhibits potent antiviral activities in HCV replicon cells. Antimicrob Agents Chemothr. 2006;50:1813–22.CrossRefGoogle Scholar
  2. 2.
    Reesink HW, Zeuzem S, Weegink CJ, Forestier N, van Vliet A, et al. Rapid decline of viral RNA in hepatitis C patients treated with VX-950: a phase Ib, placebo-controlled, randomized study. Gastroenterology. 2006;131:997–1002.CrossRefPubMedGoogle Scholar
  3. 3.
    Sarrazin C, Kieffer TL, Bartels D, Hanzelka B, Müh U, Welker M, et al. Dynamic hepatitis C virus genotypic and phenotypic changes in patients treated with the protease inhibitor telaprevir. Gastroenterology. 2007;132:1767–77.CrossRefPubMedGoogle Scholar
  4. 4.
    McHutchison JG, Everson GT, Gordon SC, Jacobson IM, Sulkowski M, Kauffman R, et al. Telaprevir with peginterferon and ribavirin for chronic HCV genotype 1 infection. N Engl J Med. 2009;360:1827–38.CrossRefPubMedGoogle Scholar
  5. 5.
    Sarrazin, Rouzier R, Wagner F, Forestier N, Larrey D, Gupta SK, et al. SCH503034, a novel hepatitis C virus protease inhibitor, plus pegylated interferon alpha-2b for genotype 1 nonresponders. Gastroenterology. 2007;132:1270–8.CrossRefPubMedGoogle Scholar
  6. 6.
    Reeink HW, Fanning GC, Farha KA, Weegink C, Van Vliet A, Van’t Klooster G, et al. Rapid HCV-RNA decline with once daily TMC435: a phase I study in healthy volunteers and hepatitis C patients. Gastroentelogy. 2010;138:913–21.CrossRefGoogle Scholar
  7. 7.
    Kumada H, Toyota J, Okanoue T, Chayama K, Tsubouchi H, Hayashi N, et al. Telaprevir with peginterferon and ribavirin for treatment-naive patients chronically infected with HCV of genotype 1 in Japan. J Hepatol. 2012;56:78–84.CrossRefPubMedGoogle Scholar
  8. 8.
    Chayama K, Hayes CN, Abe H, Miki D, Ochi H, Karino Y, et al. IL28B but not ITPA polymorphism is predictive of response to pegylated interferon, ribavirin, and telaprevir triple therapy in patients with genotype 1 hepatitis C. J Infect Dis. 2011;204:84–93.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Karino Y, Ozeki I, Hige S, Kimura M, Arakawa T, Nakajima T, et al. Telaprevir impairs renal function and increases blood ribavirin concentration during telaprevir/pegylated interferon/ribavirin therapy for chronic hepatitis C. J Viral Hepat. 2013;21(5):341–7.CrossRefGoogle Scholar
  10. 10.
    Foster GR, Hézode C, Bronowicki JP, Carosi G, Weiland O, Verlinden L, et al. Telaprevir alone or with peginterferon and ribavirin reduces HCV RNA in patients with chronic genotype 2 but not genotype 3 infections. Gastroenterology. 2011;141:881–9.CrossRefPubMedGoogle Scholar
  11. 11.
    Kumada H, Sato K, Takehara T, Nakamuta M, Ishigami M, Chayama K, et al. Efficacy of telaprevir-based therapy for difficult-to-treat patients with genotype 2 chronic hepatitis C in Japan. Hepatol Res. 2015;45:745–54.CrossRefPubMedGoogle Scholar
  12. 12.
    Akuta N, Suzuki F, Seko Y, Kawamura Y, Sezaki H, Suzuki Y, et al. Emergence of telaprevir-resistant variants detected by ultra-deep sequencing in patients infected with HCV genotype 1. J Med Virol. 2013;85:1028–36.CrossRefPubMedGoogle Scholar
  13. 13.
    Akuta N, Suzuki F, Fukushima T, Kawamura Y, Sezaki H, Suzuki Y, et al. Prediction of treatment efficacy and telaprevir-resistant variants after triple therapy in patients infected with HCV genotype 1. J Clin Microbiol. 2013;51:2862–8.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Sullivan JC, De Meyer S, Bartels DJ, Dierynck I, Zhang EZ, Spanks J, et al. Evolution of treatment-emergent resistant variants in telaprevir phase 3 clinical trials. Clin Infect Did. 2013;57:221–9.CrossRefGoogle Scholar
  15. 15.
    Sulkowski MS, Gardiner DF, Rodriquez Torres M, Reddy KR, Hassanein T, Jacobson I, et al. Sustained virologic response with daclatasvir plus sofosbuvir +/− ribavirin in chronic HCV genotype 1 infected patients who previously failed telaprevir or boceprevir. J Hepatol. 2013;58:S570.CrossRefGoogle Scholar
  16. 16.
    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;59:2083–91.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media Singapore 2017

Authors and Affiliations

  1. 1.Department of HepatologySapporo-Kosei HospitalSapporoJapan

Personalised recommendations