IP-10 predicts viral response and therapeutic outcome in... : Hepatology (original) (raw)

Viral Hepatitis

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

Lagging, Martin1,*; Romero, Ana I.1; Westin, Johan1; Norkrans, Gunnar1; Dhillon, Amar P.2; Pawlotsky, Jean-Michel3; Zeuzem, Stefan4; von Wagner, Michael4; Negro, Francesco5; Schalm, Solko W.6; Haagmans, Bart L.7; Ferrari, Carlo8; Missale, Gabriele8; Neumann, Avidan U.9; Verheij-Hart, Elke6; Hellstrand, Kristoffer1 DITTO-HCV Study Group

1_Department of Infectious Diseases, University of Göteborg, Sweden_

2_Department of Histopathology, Royal Free Hospital, London, UK_

3_Hôpital Henri Mondor–Université Paris XII, Creteil, France_

4_Saarland University Hospital, Homburg/Saar, Germany_

5_Hospital University of Genève, Genève, Switzerland_

6_University Hospital Rotterdam Dijkzigt, Rotterdam, Netherlands_

7_Department of Virology, Erasmus MC, Rotterdam_

8_Azienda Ospedaliera di Parma, Parma, Italy_

9_Bar-Ilan University, Ramat-Gan, Israel_

*Department of Infectious Diseases, Göteborg University, Guldhedsgatan 10B, SE-413 46 Göteborg, Sweden

Email:[email protected]

Received 7 April 2006; Accepted 6 September 2006

Published online in Wiley InterScience (www.interscience.wiley.com).

Grant sponsor: European Community; Grant Number: QLK2-2000-00836; Grant sponsor: The Swedish Society Against Cancer (Cancerfonden); Grant sponsor: Hoffmann-La Roche; Grant sponsor: Inga-Britt & Arne Lundberg Foundation; Grant sponsor: Swedish Society of Medicine; Grant sponsor: EpiCept Corporation.

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.

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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.