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

Martin Lagging*, Ana I. Romero, DITTO-HCV Study Group, Johan Westin, Gunnar Norkrans, Amar P. Dhillon, Jean Michel Pawlotsky, Stefan Zeuzem, Michael Von Wagner, Francesco Negro, Solko W. Schalm, Bart L. Haagmans, Carlo Ferrari, Gabriele Missale, Avidan U. Neumann, Elke Verheij-Hart, Kristoffer Hellstrand

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

189 Citations (Scopus)

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 HCY-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.

Original languageEnglish
Pages (from-to)1617-1625
Number of pages9
JournalHepatology
Volume44
Issue number6
DOIs
Publication statusPublished - Dec 2006

Bibliographical note

Copyright © 2006 by the American Association for the Study of Liver Diseases.

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