Potential role for Interleukin-28B genotype in treatment decision-making in recent hepatitis C virus infection

Authors

  • Jason Grebely,

    Corresponding author
    1. National Centre in HIV Epidemiology and Clinical Research (NCHECR), University of New South Wales (UNSW), Sydney, Australia
    • Lecturer, Viral Hepatitis Clinical Research Program, National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, 12 Leichhardt Street, Darlinghurst, NSW, 2010, Australia
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    • Fax: +61-2-9385 0876

  • Kathy Petoumenos,

    1. National Centre in HIV Epidemiology and Clinical Research (NCHECR), University of New South Wales (UNSW), Sydney, Australia
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  • Margaret Hellard,

    1. Burnet Institute, Melbourne, Australia
    2. Infectious Diseases Unit, The Alfred Hospital, Melbourne, Australia
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  • Gail V. Matthews,

    1. National Centre in HIV Epidemiology and Clinical Research (NCHECR), University of New South Wales (UNSW), Sydney, Australia
    2. HIV/Immunology/Infectious Diseases Clinical Services Unit, St Vincent's Hospital, Sydney, Australia
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  • Vijayaprakash Suppiah,

    1. Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, Sydney, Australia
    2. Institute for Immunology and Allergy Research, Westmead Millennium Institute, University of Sydney, Sydney, Australia
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  • Tanya Applegate,

    1. National Centre in HIV Epidemiology and Clinical Research (NCHECR), University of New South Wales (UNSW), Sydney, Australia
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  • Barbara Yeung,

    1. National Centre in HIV Epidemiology and Clinical Research (NCHECR), University of New South Wales (UNSW), Sydney, Australia
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  • Phillipa Marks,

    1. National Centre in HIV Epidemiology and Clinical Research (NCHECR), University of New South Wales (UNSW), Sydney, Australia
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  • William Rawlinson,

    1. Centre for Infection and Inflammation Research, School of Medical Sciences, UNSW, Sydney, Australia
    2. Virology Division, SEALS Microbiology, Prince of Wales Hospital, Sydney, Australia
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  • Andrew R. Lloyd,

    1. Centre for Infection and Inflammation Research, School of Medical Sciences, UNSW, Sydney, Australia
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  • David Booth,

    1. Institute for Immunology and Allergy Research, Westmead Millennium Institute, University of Sydney, Sydney, Australia
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  • John M. Kaldor,

    1. National Centre in HIV Epidemiology and Clinical Research (NCHECR), University of New South Wales (UNSW), Sydney, Australia
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  • Jacob George,

    1. Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, Sydney, Australia
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  • Gregory J. Dore

    1. National Centre in HIV Epidemiology and Clinical Research (NCHECR), University of New South Wales (UNSW), Sydney, Australia
    2. HIV/Immunology/Infectious Diseases Clinical Services Unit, St Vincent's Hospital, Sydney, Australia
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  • Potential conflict of interest: G.D., G.M., and J.K. have received research support from Roche Pharmaceuticals. G.D. is on the speaker's bureau for Roche Pharmaceuticals. G.D. and G.M. are members of advisory board for Roche Pharmaceuticals. G.D., P.M., and B.Y. have received travel grants from Roche Pharmaceuticals. G.D. is a consultant/advisor for Schering-Plough, Tibotec, and Abbott. J. Grebely is a member of an advisory board for Schering-Plough. G.M. is a consultant/advisor for Schering-Plough, Novartis, and Astellas.

Abstract

Polymorphisms in the IL28B (interleukin-28B) gene region are important in predicting outcome following therapy for chronic hepatitis C virus (HCV) infection. We evaluated the role of IL28B in spontaneous and treatment-induced clearance following recent HCV infection. The Australian Trial in Acute Hepatitis C (ATAHC) was a study of the natural history and treatment of recent HCV, as defined by positive anti-HCV antibody, preceded by either acute clinical HCV infection within the prior 12 months or seroconversion within the prior 24 months. Factors associated with spontaneous and treatment-induced HCV clearance, including variations in IL28B, were assessed. Among 163 participants, 132 were untreated (n = 52) or had persistent infection (infection duration ≥26 weeks) at treatment initiation (n = 80). Spontaneous clearance was observed in 23% (30 of 132 participants). In Cox proportional hazards analysis (without IL28B), HCV seroconversion illness with jaundice was the only factor predicting spontaneous clearance (adjusted hazards ratio = 2.86; 95% confidence interval = 1.24, 6.59; P = 0.014). Among participants with IL28B genotyping (n = 102 of 163 overall and 79 of 132 for the spontaneous clearance population), rs8099917 TT homozygosity (versus GT/GG) was the only factor independently predicting time to spontaneous clearance (adjusted hazard ratio = 3.78; 95% confidence interval = 1.04, 13.76; P = 0.044). Participants with seroconversion illness with jaundice were more frequently rs8099917 TT homozygotes than other (GG/GT) genotypes (32% versus 5%, P = 0.047). Among participants adherent to treatment and who had IL28B genotyping (n = 54), sustained virologic response was similar among TT homozygotes (18 of 29 participants, 62%) and those with GG/GT genotype (16 of 25, 64%, P = 0.884). Conclusion: During recent HCV infection, genetic variations in IL28B region were associated with spontaneous but not treatment-induced clearance. Early therapeutic intervention could be recommended for individuals with unfavorable IL28B genotypes. (HEPATOLOGY 2010;)

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