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Vol. 55, No. 6, 2012
Issue release date: October 2012
Section title: Original Paper
Intervirology 2012;55:417–425
(DOI:10.1159/000323526)

Amino Acid Substitution in HCV Core Region and Genetic Variation near the IL28B Gene Affect Viral Dynamics during Telaprevir, Peginterferon and Ribavirin Treatment

Akuta N. · Suzuki F. · Hirakawa M. · Kawamura Y. · Yatsuji H. · Sezaki H. · Suzuki Y. · Hosaka T. · Kobayashi M. · Kobayashi M. · Saitoh S. · Arase Y. · Ikeda K. · Chayama K. · Nakamura Y. · Kumada H.
aDepartment of Hepatology, and bLiver Research Laboratory, Toranomon Hospital, cLaboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, and dDepartment of Medical and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 8/11/2010
Accepted: 11/18/2010
Published online: 6/8/2012

Number of Print Pages: 9
Number of Figures: 2
Number of Tables: 3

ISSN: 0300-5526 (Print)
eISSN: 1423-0100 (Online)

For additional information: http://www.karger.com/INT

Abstract

Objectives: Genetic variation near the IL28B gene and substitution of aa 70 and 91 in the core region of HCV-1b are useful as predictors of treatment efficacy to telaprevir/pegylated interferon (PEG-IFN)/ribavirin, but its impact on viral dynamics is not clear. Methods: This study investigated predictive factors of viral dynamics during 12- or 24-week regimen of triple therapy in 80 Japanese adults infected with HCV-1b. Results: After 24 h of commencement of treatment, the proportion of patients with Arg70 and Leu91 substitutions in the core region who showed ≥3.0 log drop in HCV RNA level was significantly higher than that of patients with Gln70 (His70) and/or Met91. At 8 and 12 weeks, HCV RNA loss rate of patients with rs8099917 genotype TT near IL28B gene was significantly higher than that of patients with non-TT. Multivariate analysis identified substitution of aa 70 and 91 as a predictor of ≥3.0 log fall in HCV RNA level at 24 h (Arg70 and Leu91) and SVR (Arg70), and rs8099917 (TT) as a predictor of HCV RNA loss at 12 weeks and SVR. Conclusions: This study identified genetic variation near IL28B gene and aa substitution of the core region as predictors of viral dynamics during triple therapy.


  

Author Contacts

Norio Akuta, MD
Department of Hepatology, Toranomon Hospital
2-2-2 Toranomon, Minato-ku
Tokyo 105-0001 (Japan)
Tel. +81 44 877 5111, E-Mail akuta-gi@umin.ac.jp

  

Article Information

Received: August 11, 2010
Accepted after revision: November 18, 2010
Published online: June 8, 2012
Number of Print Pages : 9
Number of Figures : 2, Number of Tables : 3, Number of References : 33

  

Publication Details

Intervirology (International Journal of Basic and Medical Virology)

Vol. 55, No. 6, Year 2012 (Cover Date: October 2012)

Journal Editor: Liebert U.G. (Leipzig), Manuguerra J.-C. (Paris)
ISSN: 0300-5526 (Print), eISSN: 1423-0100 (Online)

For additional information: http://www.karger.com/INT


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 8/11/2010
Accepted: 11/18/2010
Published online: 6/8/2012

Number of Print Pages: 9
Number of Figures: 2
Number of Tables: 3

ISSN: 0300-5526 (Print)
eISSN: 1423-0100 (Online)

For additional information: http://www.karger.com/INT


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