25. New Horizons: IL28, Direct-Acting Antiviral Therapy for HCV

  1. Geoffrey W. McCaughan MBBS, PhD, FRACP4,5,
  2. John G. McHutchison MD6 and
  3. Jean-Michel Pawlotsky MD, PhD7,8
  1. Alexander J. Thompson MD, PhD1,2,3,
  2. John G. McHutchison MD6 and
  3. Geoffrey W. McCaughan MBBS, PhD, FRACP4,5

Published Online: 3 NOV 2011

DOI: 10.1002/9781444346343.ch25

Advanced Therapy for Hepatitis C

Advanced Therapy for Hepatitis C

How to Cite

Thompson, A. J., McHutchison, J. G. and McCaughan, G. W. (2011) New Horizons: IL28, Direct-Acting Antiviral Therapy for HCV, in Advanced Therapy for Hepatitis C (eds G. W. McCaughan, J. G. McHutchison and J.-M. Pawlotsky), Wiley-Blackwell, Oxford, UK. doi: 10.1002/9781444346343.ch25

Editor Information

  1. 4

    Centenary Research Institute, Sydney, NSW, Australia

  2. 5

    Royal Prince Alfred Hospital, University of Sydney, Sydney, NSW, Australia

  3. 6

    Liver Disease Therapeutics, Gilead Sciences, Inc., Foster City, CA, USA

  4. 7

    French National Reference Center for Viral Hepatitis B, C and delta, Créteil, France

  5. 8

    Department of Virology, Bacteriology, and Hygiene, INSERM U955, Hôpital Henri Mondor, Université Paris Est, Créteil, France

Author Information

  1. 1

    St. Vincent's Hospital Melbourne, University of Melbourne, Melbourne, VIC, Australia

  2. 2

    Victorian Infectious Diseases Reference Laboratory (VIDRL), North Melbourne, VIC, Australia

  3. 3

    Department of Gastroenterology and Duke Clinical Research Institute, Duke University, Durham, NC, USA

  4. 4

    Centenary Research Institute, Sydney, NSW, Australia

  5. 5

    Royal Prince Alfred Hospital, University of Sydney, Sydney, NSW, Australia

  6. 6

    Liver Disease Therapeutics, Gilead Sciences, Inc., Foster City, CA, USA

Publication History

  1. Published Online: 3 NOV 2011
  2. Published Print: 24 NOV 2011

ISBN Information

Print ISBN: 9781405187459

Online ISBN: 9781444346343

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Keywords:

  • hepatitis C;
  • HCV;
  • NS3;
  • NS5;
  • protease inhibitor;
  • polymerase inhibitor;
  • cyclophilin inhibitor;
  • interferon;
  • IL28

Summary

The current standard-of-care for the treatment of chronic hepatitis C is pegylated interferon alfa and ribavirin. Unfortunately efficacy is limited and at best 50% of Western patients infected with genotype 1 HCV are cured. The need for more effective treatment has driven the development of direct-acting antiviral agents (DAA) that target specific steps in the viral replication cycle. Over 50 investigational agents are currently in clinical development. The NS3/4A protease inhibitors telaprevir and boceprevir are the first to have completed phase III programs and are expected to be licenced in the near future. Triple therapy with peg-IFN and RBV will increase sustained virologic response rates for genotype 1 HCV, and in many patients allow shortened duration of therapy. Promising next-generation candidates include inhibitors of the HCV NS5B polymerase and the NS5A phosphoprotein, and IFN-free combination regimens are being investigated. However, the introduction of DAA will not be without challenges, including antiviral resistance, drug toxicity, and the need to optimize and rationalize treatment algorithms in the face of a rapidly evolving therapeutic arsenal.