IP-10 predicts viral response and therapeutic outcome in difficult-to-treat patients with HCV genotype 1 infection

Authors

  • Martin Lagging,

    Corresponding author
    1. Department of Infectious Diseases, University of Göteborg, Sweden
    • Department of Infectious Diseases, Göteborg University, Guldhedsgatan 10B, SE-413 46 Göteborg, Sweden
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    • fax: (46) 31-41-12-56

  • Ana I. Romero,

    1. Department of Infectious Diseases, University of Göteborg, Sweden
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  • Johan Westin,

    1. Department of Infectious Diseases, University of Göteborg, Sweden
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  • Gunnar Norkrans,

    1. Department of Infectious Diseases, University of Göteborg, Sweden
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  • Amar P. Dhillon,

    1. Department of Histopathology, Royal Free Hospital, London, UK
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  • Jean-Michel Pawlotsky,

    1. Hôpital Henri Mondor–Université Paris XII, Creteil, France
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    • Potential conflict of interest: Dr. Pawlotsky is a consultant for, advises, and received grants from Gilead, Roche, Schering-Plough, and Vertex. He also received grants from Isis and Prometheus Lab. He is a consultant and advises for Abbott, Akors, Bristol-Myers Squibb, GlaxoSmithKline, Human Genome Sciences, Idenix, Idun Pharmaceuticals, InterMune, Novartis, Valeant, and XTL Biopharmaceuticals. Dr. Zeuzem is a consultant for, advises, is on the speakers' bureau of, and received grants from Schering-Plough and Roche. Dr. Hellstrand owns stock in, advises, and holds intellectual property rights with Epicept. Dr. Neumann is on the speaker's bureau of and received grants from Roche. He is on the speakers' bureau of Schering-Plough. He advises for, received grants, and is on the speaker's bureau of HGSI.

  • Stefan Zeuzem,

    1. Saarland University Hospital, Homburg/Saar, Germany
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    • Potential conflict of interest: Dr. Pawlotsky is a consultant for, advises, and received grants from Gilead, Roche, Schering-Plough, and Vertex. He also received grants from Isis and Prometheus Lab. He is a consultant and advises for Abbott, Akors, Bristol-Myers Squibb, GlaxoSmithKline, Human Genome Sciences, Idenix, Idun Pharmaceuticals, InterMune, Novartis, Valeant, and XTL Biopharmaceuticals. Dr. Zeuzem is a consultant for, advises, is on the speakers' bureau of, and received grants from Schering-Plough and Roche. Dr. Hellstrand owns stock in, advises, and holds intellectual property rights with Epicept. Dr. Neumann is on the speaker's bureau of and received grants from Roche. He is on the speakers' bureau of Schering-Plough. He advises for, received grants, and is on the speaker's bureau of HGSI.

  • Michael von Wagner,

    1. Saarland University Hospital, Homburg/Saar, Germany
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  • Francesco Negro,

    1. Hospital University of Genève, Genève, Switzerland
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  • Solko W. Schalm,

    1. University Hospital Rotterdam Dijkzigt, Rotterdam, Netherlands
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  • Bart L. Haagmans,

    1. Department of Virology, Erasmus MC, Rotterdam
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  • Carlo Ferrari,

    1. Azienda Ospedaliera di Parma, Parma, Italy
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  • Gabriele Missale,

    1. Azienda Ospedaliera di Parma, Parma, Italy
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  • Avidan U. Neumann,

    1. Bar-Ilan University, Ramat-Gan, Israel
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    • Potential conflict of interest: Dr. Pawlotsky is a consultant for, advises, and received grants from Gilead, Roche, Schering-Plough, and Vertex. He also received grants from Isis and Prometheus Lab. He is a consultant and advises for Abbott, Akors, Bristol-Myers Squibb, GlaxoSmithKline, Human Genome Sciences, Idenix, Idun Pharmaceuticals, InterMune, Novartis, Valeant, and XTL Biopharmaceuticals. Dr. Zeuzem is a consultant for, advises, is on the speakers' bureau of, and received grants from Schering-Plough and Roche. Dr. Hellstrand owns stock in, advises, and holds intellectual property rights with Epicept. Dr. Neumann is on the speaker's bureau of and received grants from Roche. He is on the speakers' bureau of Schering-Plough. He advises for, received grants, and is on the speaker's bureau of HGSI.

  • Elke Verheij-Hart,

    1. University Hospital Rotterdam Dijkzigt, Rotterdam, Netherlands
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  • Kristoffer Hellstrand

    1. Department of Infectious Diseases, University of Göteborg, Sweden
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    • Potential conflict of interest: Dr. Pawlotsky is a consultant for, advises, and received grants from Gilead, Roche, Schering-Plough, and Vertex. He also received grants from Isis and Prometheus Lab. He is a consultant and advises for Abbott, Akors, Bristol-Myers Squibb, GlaxoSmithKline, Human Genome Sciences, Idenix, Idun Pharmaceuticals, InterMune, Novartis, Valeant, and XTL Biopharmaceuticals. Dr. Zeuzem is a consultant for, advises, is on the speakers' bureau of, and received grants from Schering-Plough and Roche. Dr. Hellstrand owns stock in, advises, and holds intellectual property rights with Epicept. Dr. Neumann is on the speaker's bureau of and received grants from Roche. He is on the speakers' bureau of Schering-Plough. He advises for, received grants, and is on the speaker's bureau of HGSI.


Abstract

Plasma from 173 patients with HCV genotype 1 infection was analyzed for IP-10 levels prior to treatment with pegylated interferon-α-2a and ribavirin. Significantly lower IP-10 levels were observed in patients achieving a rapid viral response (RVR) (P < .0001), even in those with body mass index (BMI) ≥ 25 kg/m2 (P = .004) and with baseline viral load ≥ 2 million IU/mL (P = .001). Similarly, significantly lower IP-10 levels were observed in patients obtaining a sustained viral response (SVR) (P = .0002), including those having higher BMI (P < .05), higher viral load (P = .0005), and both higher BMI and viral load (P < .03). In multivariate logistic regression analyses, a low IP-10 value was independently predictive of both RVR and SVR. A baseline cutoff IP-10 value of 600 pg/mL yielded a negative predictive value (NPV) of 79% (19/24) for all genotype 1–infected patients, which was comparable with that observed using a reduction in HCV-RNA by at least 2 logs after 12 weeks of therapy (NPV 86%; 19/22); by combining the two, 30 of 38 patients (NPV 79%) potentially could have been spared unnecessary therapy. In patients having both higher BMI and viral load, cut-off levels of 150 and 600 pg/mL yielded a positive predictive value (PPV) of 71% and NPV of 100%, respectively. In conclusion, pretreatment IP-10 levels predict RVR and SVR in patients infected with HCV genotype 1, even in those with higher BMI and viral load. A substantial proportion of the latter patients may achieve SVR in spite of unfavorable baseline characteristics if their pretreatment IP-10 level is low. Thus, pretreatment IP-10 analysis may prove helpful in decision-making regarding pharmaceutical intervention. (HEPATOLOGY 2006;44:1617–1625.)

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