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Interleukin-28B single nucleotide polymorphism of donors and recipients can predict viral response to pegylated interferon/ribavirin therapy in patients with recurrent hepatitis C after living donor liver transplantation

Authors

  • Tomokazu Kawaoka,

    1. Department of Medicine and Molecular Science, Hiroshima University, Hiroshima, Japan
    2. Laboratory for Digestive Diseases, Center for Genomic Medicine, RIKEN (The Institute of Physical and Chemical Research), Hiroshima, Japan
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  • Shoichi Takahashi,

    Corresponding author
    1. Laboratory for Digestive Diseases, Center for Genomic Medicine, RIKEN (The Institute of Physical and Chemical Research), Hiroshima, Japan
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  • Shintaro Takaki,

    1. Laboratory for Digestive Diseases, Center for Genomic Medicine, RIKEN (The Institute of Physical and Chemical Research), Hiroshima, Japan
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  • Akira Hiramatsu,

    1. Laboratory for Digestive Diseases, Center for Genomic Medicine, RIKEN (The Institute of Physical and Chemical Research), Hiroshima, Japan
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  • Koji Waki,

    1. Laboratory for Digestive Diseases, Center for Genomic Medicine, RIKEN (The Institute of Physical and Chemical Research), Hiroshima, Japan
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  • Nobuhiko Hiraga,

    1. Department of Medicine and Molecular Science, Hiroshima University, Hiroshima, Japan
    2. Laboratory for Digestive Diseases, Center for Genomic Medicine, RIKEN (The Institute of Physical and Chemical Research), Hiroshima, Japan
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  • Daiki Miki,

    1. Department of Medicine and Molecular Science, Hiroshima University, Hiroshima, Japan
    2. Laboratory for Digestive Diseases, Center for Genomic Medicine, RIKEN (The Institute of Physical and Chemical Research), Hiroshima, Japan
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  • Masataka Tsuge,

    1. Department of Medicine and Molecular Science, Hiroshima University, Hiroshima, Japan
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  • Michio Imamura,

    1. Department of Medicine and Molecular Science, Hiroshima University, Hiroshima, Japan
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  • Yoshiiku Kawakami,

    1. Department of Medicine and Molecular Science, Hiroshima University, Hiroshima, Japan
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  • Hiroshi Aikata,

    1. Department of Medicine and Molecular Science, Hiroshima University, Hiroshima, Japan
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  • Hidenori Ochi,

    1. Department of Medicine and Molecular Science, Hiroshima University, Hiroshima, Japan
    2. Laboratory for Digestive Diseases, Center for Genomic Medicine, RIKEN (The Institute of Physical and Chemical Research), Hiroshima, Japan
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  • Takashi Onoe,

    1. Department of Medicine and Molecular Science, Hiroshima University, Hiroshima, Japan
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  • Hirotaka Tashiro,

    1. Department of Surgery, Hiroshima University, Hiroshima, Japan
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  • Hideki Ohdan,

    1. Department of Surgery, Hiroshima University, Hiroshima, Japan
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  • Kazuaki Chayama

    1. Department of Medicine and Molecular Science, Hiroshima University, Hiroshima, Japan
    2. Laboratory for Digestive Diseases, Center for Genomic Medicine, RIKEN (The Institute of Physical and Chemical Research), Hiroshima, Japan
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Dr Shoichi Takahashi, Department of Medicine and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8551, Japan. Email: shoichit@hiroshima-u.ac.jp

Abstract

Background and Aim:  Interleukin-28B (IL28B) single nucleotide polymorphism (SNP) influences viral response (VR) to interferon (IFN) therapy in patients with hepatitis C. We studied the relationship between VR and the IL28B polymorphism (rs8099917) in patients on long-term pegylated IFN plus ribavirin (PEGIFN/RBV) therapy for recurrent hepatitis C after living-donor liver transplantation (LDLT).

Methods:  Thirty-five patients with recurrent hepatitis C after LDLT were treated with PEGIFN/RBV. We evaluated the effect of IL28B SNP on the outcome in 20 patients infected with hepatitis C virus genotype 1 who completed IFN therapy.

Results:  The sustained VR (SVR) rate was 54% (19/35) for all patients; 46% (13/28) for genotype 1. The SVR rate of donors' TT group (major genotype) was higher than that of donors' TG + GG group (minor genotype) (73% vs 20%), while that of recipients' TT group was similar to that of recipients' TG + GG group (64% vs 50%). With regard to the combined effect of donors' and recipients' IL28B SNP, the SVR rates of TT : TT (donors' : recipients'), TT : TG + GG, TG + GG : any group were 81%, 50%, and 20%, respectively. The VR rate of TT : TT, TT : TG + GG and TG + GG : any group at 12 weeks were 28%, 0%, and 0%; those at 48 weeks were 70%, 50%, 20%, and those at the end of treatment were 100%, 50%, 20%, respectively. The multivariate analysis identified IL28B of donors : recipients (TT : TT) as the only independent determinant of SVR (odds ratio 15.0, P = 0.035).

Conclusion:  Measurement of donors' and recipients' IL28B SNP can predict the response to PEGIFN/RBV therapy, and the donors' IL28B SNP might be a more significant predictor than that of the recipients.

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