Quantitation of pretreatment serum interferon-γ–inducible protein-10 improves the predictive value of an IL28B gene polymorphism for hepatitis C treatment response

Authors

  • Jama M. Darling,

    1. University of North Carolina, Chapel Hill, NC
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  • Jeroen Aerssens,

    1. Tibotec BVBA, Mechelen, Belgium
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  • Gregory Fanning,

    1. Tibotec BVBA, Mechelen, Belgium
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    • Potential conflict of interest: J. Aerssens, G. Fanning, W. Talloen, J. Bollekens, M. De Wit, and A. Scholliers are employees of Tibotec BVBA. D. B. Goldstein, K. V. Shianna, J. G. McHutchison, and A. J. Thompson are coinventors of an IL28B patent application. M. W. Fried, G. Fanning, and J. Aerssens are coinventors on a patent application using IP-10 and IL28B to predict antiviral response. M. W. Fried serves as an ad hoc consultant to Tibotec BVBA.

  • John G. McHutchison,

    1. Duke University, Durham, NC
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    • Potential conflict of interest: J. Aerssens, G. Fanning, W. Talloen, J. Bollekens, M. De Wit, and A. Scholliers are employees of Tibotec BVBA. D. B. Goldstein, K. V. Shianna, J. G. McHutchison, and A. J. Thompson are coinventors of an IL28B patent application. M. W. Fried, G. Fanning, and J. Aerssens are coinventors on a patent application using IP-10 and IL28B to predict antiviral response. M. W. Fried serves as an ad hoc consultant to Tibotec BVBA.

  • David B. Goldstein,

    1. Duke University, Durham, NC
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    • Potential conflict of interest: J. Aerssens, G. Fanning, W. Talloen, J. Bollekens, M. De Wit, and A. Scholliers are employees of Tibotec BVBA. D. B. Goldstein, K. V. Shianna, J. G. McHutchison, and A. J. Thompson are coinventors of an IL28B patent application. M. W. Fried, G. Fanning, and J. Aerssens are coinventors on a patent application using IP-10 and IL28B to predict antiviral response. M. W. Fried serves as an ad hoc consultant to Tibotec BVBA.

  • Alexander J. Thompson,

    1. Duke University, Durham, NC
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    • Potential conflict of interest: J. Aerssens, G. Fanning, W. Talloen, J. Bollekens, M. De Wit, and A. Scholliers are employees of Tibotec BVBA. D. B. Goldstein, K. V. Shianna, J. G. McHutchison, and A. J. Thompson are coinventors of an IL28B patent application. M. W. Fried, G. Fanning, and J. Aerssens are coinventors on a patent application using IP-10 and IL28B to predict antiviral response. M. W. Fried serves as an ad hoc consultant to Tibotec BVBA.

  • Kevin V. Shianna,

    1. Duke University, Durham, NC
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    • Potential conflict of interest: J. Aerssens, G. Fanning, W. Talloen, J. Bollekens, M. De Wit, and A. Scholliers are employees of Tibotec BVBA. D. B. Goldstein, K. V. Shianna, J. G. McHutchison, and A. J. Thompson are coinventors of an IL28B patent application. M. W. Fried, G. Fanning, and J. Aerssens are coinventors on a patent application using IP-10 and IL28B to predict antiviral response. M. W. Fried serves as an ad hoc consultant to Tibotec BVBA.

  • Nezam H. Afdhal,

    1. Harvard Medical School, Boston, MA
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  • Michael L. Hudson,

    1. University of North Carolina, Chapel Hill, NC
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  • Charles D. Howell,

    1. University of Maryland, College Park, MD
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  • Willem Talloen,

    1. Johnson & Johnson Pharmaceutical R&D, Janssen Pharmaceutica NV, Beerse, Belgium
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    • Potential conflict of interest: J. Aerssens, G. Fanning, W. Talloen, J. Bollekens, M. De Wit, and A. Scholliers are employees of Tibotec BVBA. D. B. Goldstein, K. V. Shianna, J. G. McHutchison, and A. J. Thompson are coinventors of an IL28B patent application. M. W. Fried, G. Fanning, and J. Aerssens are coinventors on a patent application using IP-10 and IL28B to predict antiviral response. M. W. Fried serves as an ad hoc consultant to Tibotec BVBA.

  • Jacques Bollekens,

    1. Tibotec BVBA, Mechelen, Belgium
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    • Potential conflict of interest: J. Aerssens, G. Fanning, W. Talloen, J. Bollekens, M. De Wit, and A. Scholliers are employees of Tibotec BVBA. D. B. Goldstein, K. V. Shianna, J. G. McHutchison, and A. J. Thompson are coinventors of an IL28B patent application. M. W. Fried, G. Fanning, and J. Aerssens are coinventors on a patent application using IP-10 and IL28B to predict antiviral response. M. W. Fried serves as an ad hoc consultant to Tibotec BVBA.

  • Mieke De Wit,

    1. Tibotec BVBA, Mechelen, Belgium
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    • Potential conflict of interest: J. Aerssens, G. Fanning, W. Talloen, J. Bollekens, M. De Wit, and A. Scholliers are employees of Tibotec BVBA. D. B. Goldstein, K. V. Shianna, J. G. McHutchison, and A. J. Thompson are coinventors of an IL28B patent application. M. W. Fried, G. Fanning, and J. Aerssens are coinventors on a patent application using IP-10 and IL28B to predict antiviral response. M. W. Fried serves as an ad hoc consultant to Tibotec BVBA.

  • Annick Scholliers,

    1. Tibotec BVBA, Mechelen, Belgium
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    • Potential conflict of interest: J. Aerssens, G. Fanning, W. Talloen, J. Bollekens, M. De Wit, and A. Scholliers are employees of Tibotec BVBA. D. B. Goldstein, K. V. Shianna, J. G. McHutchison, and A. J. Thompson are coinventors of an IL28B patent application. M. W. Fried, G. Fanning, and J. Aerssens are coinventors on a patent application using IP-10 and IL28B to predict antiviral response. M. W. Fried serves as an ad hoc consultant to Tibotec BVBA.

  • Michael W. Fried

    Corresponding author
    1. University of North Carolina, Chapel Hill, NC
    • University of North Carolina, CB# 7584, Room 8015, Burnett Womack Building, Chapel Hill, NC 27599
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    • Potential conflict of interest: J. Aerssens, G. Fanning, W. Talloen, J. Bollekens, M. De Wit, and A. Scholliers are employees of Tibotec BVBA. D. B. Goldstein, K. V. Shianna, J. G. McHutchison, and A. J. Thompson are coinventors of an IL28B patent application. M. W. Fried, G. Fanning, and J. Aerssens are coinventors on a patent application using IP-10 and IL28B to predict antiviral response. M. W. Fried serves as an ad hoc consultant to Tibotec BVBA.

    • fax: 919-966-1700


  • Supported in part by National Institutes of Health Mid-Career Mentoring Award K24 DK066144 (to M. W. Fried).

Abstract

Polymorphisms of the IL28B gene are highly associated with sustained virological response (SVR) in patients with chronic hepatitis C treated with peginterferon and ribavirin. Quantitation of interferon-γ–inducible protein-10 (IP-10) may also differentiate antiviral response. We evaluated IP-10 levels in pretreatment serum from 115 nonresponders and 157 sustained responders in the Study of Viral Resistance to Antiviral Therapy of Chronic Hepatitis C cohort, including African American (AA) and Caucasian American (CA) patients. Mean IP-10 was lower in sustained responders compared with nonresponders (437 ± 31 vs 704 ± 44 pg/mL, P< 0.001), both in AA and CA patients. The positive predictive value of low IP-10 levels (<600 pg/mL) for SVR was 69%, whereas the negative predictive value of high IP-10 levels (>600 pg/mL) was 67%. We assessed the combination of pretreatment IP-10 levels with IL28B genotype as predictors of treatment response. The IL28B polymorphism rs12979860 was tested in 210 participants. The CC, CT, and TT genotypes were found in 30%, 49%, and 21% of patients, respectively, with corresponding SVR rates of 87%, 50%, and 39% (P< 0.0001). Serum IP-10 levels within the IL28B genotype groups provided additional information regarding the likelihood of SVR (P< 0.0001). CT carriers with low IP-10 had 64% SVR versus 24% with high IP-10. Similarly, a higher SVR rate was identified for TT and CC carriers with low versus high IP-10 (TT, 48% versus 20%; CC, 89% versus 79%). IL28B genotype and baseline IP-10 levels were additive but independent when predicting SVR in both AA and CA patients. Conclusion: When IL28B genotype is combined with pretreatment serum IP-10 measurement, the predictive value for discrimination between SVR and nonresponse is significantly improved, especially in non-CC genotypes. This relationship warrants further investigation to elucidate the mechanisms of antiviral response and prospective validation. (Hepatology 2011;)

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