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HCV substitutions and IL28B polymorphisms on outcome of peg-interferon plus ribavirin combination therapy
  1. C Nelson Hayes1,2,
  2. Mariko Kobayashi3,
  3. Norio Akuta3,
  4. Fumitaka Suzuki3,
  5. Hiromitsu Kumada3,
  6. Hiromi Abe1,2,
  7. Daiki Miki1,2,
  8. Michio Imamura1,2,
  9. Hidenori Ochi1,2,
  10. Naoyuki Kamatani4,
  11. Yusuke Nakamura5,
  12. Kazuaki Chayama1,2
  1. 1Laboratory for Digestive Diseases, Center for Genomic Medicine, RIKEN, Hiroshima, Japan
  2. 2Department of Medicine and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
  3. 3Department of Hepatology, Toranomon Hospital, Tokyo, Japan
  4. 4Center for Genomic Medicine, Riken, Yokohama, Japan
  5. 5Laboratory of Molecular Medicine, Human Genome Center, The Institute of Medical Science, University of Tokyo, Tokyo, Japan
  1. Correspondence to Professor Kazuaki Chayama, Department of Medical and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan; chayama{at}hiroshima-u.ac.jp

Abstract

Background and aims A number of recent studies have shown that human polymorphisms near the IL28B type III interferon (IFNλ) gene influence the response to peg-interferon plus ribavirin combination therapy for infection with chronic hepatitis C virus (HCV). Viral polymorphisms, including substitutions within the HCV core and NS5A proteins, have also been shown to influence treatment outcome, but it is not known whether these factors act independently of the IL28B polymorphism or if they reflect the same or a different underlying mechanism. Multiple logistic regression was used to determine whether host and viral polymorphisms independently predict sustained virological response (SVR).

Methods Two single nucleotide polymorphisms were genotyped in the IL28B locus (rs12979860 and rs8099917) from 817 patients with chronic HCV infection, and substitutions at amino acids 70 and 91 of the HCV core protein and within the NS5A interferon sensitivity-determining region (ISDR) were analysed.

Results It was found that independent predictors of an SVR included IL28B rs12979860 CC genotype (OR=4.98; p=4.00E-08), core amino acid 70 substitutions (OR=0.53; p=0.016), age and baseline viral load. For non-virological response, the IL28B rs12979860 CT/TT genotype (OR=0.23; p=1.96E-8) and age were independent predictors. IL28B rs12979860 genotype (p=1.4E-8), core amino acid 70 substitutions (p=0.0013), ISDR substitutions (p=0.0019), baseline viral load, γ-glutamyltranspeptidase, alanine aminotransferase and platelet count were independent predictors for change in viral load by week 4 of treatment.

Conclusions IL28B polymorphisms and HCV core amino acid 70 substitutions contribute independently to an SVR to peg-interferon plus ribavirin combination therapy.

  • Interferon sensitivity-determining region
  • HCV core protein
  • type III interferon
  • genotype 1b
  • sustained virological response
  • chronic hepatitis
  • genetic polymorphisms
  • HCV
  • interferon
  • interleukins

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Footnotes

  • Funding This work was supported in part by Grants-in-Aid for scientific research and development from the Ministry of Health, Labor and Welfare, Government of Japan.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the Hiroshima University ethics committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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