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Sequences in the interferon sensitivity-determining region and core region of hepatitis C virus impact pretreatment prediction of response to PEG-interferon plus ribavirin: Data mining analysis.

Sequences in the interferon sensitivity-determining region and core region of hepatitis C virus impact pretreatment prediction of response to PEG-interferon plus ribavirin: Data mining analysis.

Authors :
Kurosaki, Masayuki
Sakamoto, Naoya
Iwasaki, Manabu
Sakamoto, Minoru
Suzuki, Yoshiyuki
Hiramatsu, Naoki
Sugauchi, Fuminaka
Tamori, Akihiro
Nakagawa, Mina
Izumi, Namiki
Source :
Journal of Medical Virology; Mar2011, Vol. 83 Issue 3, p445-452, 8p
Publication Year :
2011

Abstract

The aim of the present study was to clarify the significance of viral factors for pretreatment prediction of sustained virological response to pegylated-interferon (PEG-IFN) plus ribavirin (RBV) therapy for chronic hepatitis C using data mining analysis. Substitutions in the IFN sensitivity-determining region (ISDR) and at position 70 of the HCV core region (Core70) were determined in 505 patients with genotype 1b chronic hepatitis C treated with PEG-IFN plus RBV. Data mining analysis was used to build a predictive model of sustained virological response in patients selected randomly (n = 304). The reproducibility of the model was validated in the remaining 201 patients. Substitutions in ISDR (odds ratio = 9.92, P < 0.0001) and Core70 (odds ratio = 1.92, P = 0.01) predicted sustained virological response independent of other covariates. The decision-tree model revealed that the rate of sustained virological response was highest (83%) in patients with two or more substitutions in ISDR. The overall rate of sustained virological response was 44% in patients with a low number of substitutions in ISDR (0-1) but was 83% in selected subgroups of younger patients (<60 years), wild-type sequence at Core70, and higher level of low-density lipoprotein cholesterol (LDL-C) (≥120 mg/dl). Reproducibility of the model was validated (r = 0.94, P < 0.001). In conclusion, substitutions in ISDR and Core70 of HCV are significant predictors of response to PEG-IFN plus RBV therapy. A decision-tree model that includes these viral factors as predictors could identify patients with a high probability of sustained virological response. J. Med. Virol. 83:445-452, 2011. © 2011 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
01466615
Volume :
83
Issue :
3
Database :
Complementary Index
Journal :
Journal of Medical Virology
Publication Type :
Academic Journal
Accession number :
57509944
Full Text :
https://doi.org/10.1002/jmv.22005