Gastroenterology
Volume 139, Issue 3 , Pages 821-827.e1 , September 2010

An IL28B Polymorphism Determines Treatment Response of Hepatitis C Virus Genotype 2 or 3 Patients Who Do Not Achieve a Rapid Virologic Response

  • Alessandra Mangia

      Affiliations

    • Liver Unit, Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy
    • Corresponding Author InformationReprint requests Address requests for reprints to: Alessandra Mangia, MD, Gastroenterology Unit, IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy. fax: (39) 0882-455161
    • ,
  • Alexander J. Thompson

      Affiliations

    • Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina
    • ,
  • Rosanna Santoro

      Affiliations

    • Liver Unit, Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy
    • ,
  • Valeria Piazzolla

      Affiliations

    • Liver Unit, Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy
    • ,
  • Hans L. Tillmann

      Affiliations

    • Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina
    • ,
  • Keyur Patel

      Affiliations

    • Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina
    • ,
  • Kevin V. Shianna

      Affiliations

    • Institute for Genome Sciences & Policy, Center for Human Genome Variation, Duke University Medical Center, Durham, North Carolina
    • ,
  • Leonardo Mottola

      Affiliations

    • Liver Unit, Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy
    • ,
  • Daniela Petruzzellis

      Affiliations

    • Liver Unit, Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy
    • ,
  • Donato Bacca

      Affiliations

    • Department of Internal Medicine, Hospital Casarano, Italy
    • ,
  • Vito Carretta

      Affiliations

    • Department of Internal Medicine, Hospital Venosa, Venosa, Italy
    • ,
  • Nicola Minerva

      Affiliations

    • Department of Internal Medicine, Hospital Canosa, Canosa, Italy
    • ,
  • David B. Goldstein

      Affiliations

    • Institute for Genome Sciences & Policy, Center for Human Genome Variation, Duke University Medical Center, Durham, North Carolina
    • ,
  • John G. McHutchison

      Affiliations

    • Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina

Received 17 February 2010 ,Accepted 25 May 2010.

References 

  1. Ge D, Fellay J, Thompson AJ, et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature. 2009;461:399–401
  2. Tanaka Y, Nishida N, Sugiyama M, et al. Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C. Nat Genet. 2009;41:1105–1109
  3. Suppiah V, Moldovan M, Ahlenstiel G, et al. IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy. Nat Genet. 2009;41:1100–1104
  4. Ghany MG, Strader DB, Thomas DL, et al. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology. 2009;49:1335–1374
  5. Mangia A, Santoro R, Minerva N, et al. Peginterferon alfa-2b and ribavirin for 12 vs. 24 weeks in HCV genotype 2 or 3. N Engl J Med. 2005;352:2609–2617
  6. Dalgard O, Bjoro K, Ring-Larsen H, et al. Pegylated interferon alfa and ribavirin for 14 versus 24 weeks in patients with hepatitis C virus genotype 2 or 3 and rapid virological response. Hepatology. 2008;47:35–42
  7. von Wagner M, Huber M, Berg T, et al. Peginterferon-alpha-2a (40KD) and ribavirin for 16 or 24 weeks in patients with genotype 2 or 3 chronic hepatitis C. Gastroenterology. 2005;129:522–527
  8. Shiffman ML, Suter F, Bacon BR, et al. Peginterferon alfa-2a and ribavirin for 16 or 24 weeks in HCV genotype 2 or 3. N Engl J Med. 2007;357:124–134
  9. Siebert U, Sroczynski G, Aidelsburger P, et al. Clinical effectiveness and cost effectiveness of tailoring chronic hepatitis C treatment with peginterferon alpha-2b plus ribavirin to HCV genotype and early viral response: a decision analysis based on German guidelines. Pharmacoeconomics. 2009;27:341–354
  10. Zeuzem S, Berg T, Moeller B, et al. Expert opinion on the treatment of patients with chronic hepatitis C. J Viral Hepat. 2009;16:75–90
  11. de Bruijne J, Buster EH, Gelderblom HC, et al. Treatment of chronic hepatitis C virus infection—Dutch national guidelines. Neth J Med. 2008;66:311–322
  12. Scheuer PJ. Classification of chronic viral hepatitis: a need for reassessment. J Hepatol. 1991;13:372–374
  13. Thomas DL, Thio CL, Martin MP, et al. Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature. 2009;461:798–801
  14. Thompson AJ, Muir A, Sulkowski M, et al. Genome wide analysis of patients from the IDEAL study identifies a polymorphism upstream of the IL28B (=IFN-lambda-3) gene that is strongly associated with SVR in patients with HCV-1. Hepatology. 2009;50:LB5
  15. Rauch A, Kutalik Z, Descombes P, et al. Genetic variation in IL28B is associated with chronic hepatitis C and treatment failure—a genome-wide association study. Gastroenterology. 2010;138:1338–1345
  16. Kotenko SV, Gallagher G, Baurin VV, et al. IFN-lambdas mediate antiviral protection through a distinct class II cytokine receptor complex. Nat Immunol. 2003;4:69–77
  17. Sheppard P, Kindsvogel W, Xu W, et al. IL-28, IL-29 and their class II cytokine receptor IL-28R. Nat Immunol. 2003;4:63–68
  18. Robek MD, Boyd BS, Chisari FV. Lambda interferon inhibits hepatitis B and C virus replication. J Virol. 2005;79:3851–3854
  19. Shiffman ML, Lawitz E, Zaman A, et al. PEG-IFN-λ: antiviral activity and safety profile in a 4-week phase 1b study in relapsed genotype 1 hepatitis C infection. J Hepatol. 2009;50(Suppl 1):s237;(A643)

 View this article's video abstract atwww.gastrojournal.org

 Conflicts of interest These authors disclose the following: Alexander Thompson, Kevin Shianna, David Goldstein, and John McHutchison are co-inventors of a patent application based on the interleukin-28B discovery. The remaining authors disclose no conflicts.

 Funding Supported by funding from the Duke Clinical Research Institute, a generous research gift from the Richard B. Boebel Family Fund, the National Health and Medical Research Council of Australia, the Gastroenterology Society of Australia, and the Royal Australasian College of Physicians (A.J.T.).

PII: S0016-5085(10)00841-3

doi: 10.1053/j.gastro.2010.05.079

Gastroenterology
Volume 139, Issue 3 , Pages 821-827.e1 , September 2010

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