Objective: Hepatitis C virus (HCV genome) polymorphisms are thought to influence the outcome of pegylated-interferon/ribavirin (PEG-IFN/RBV) therapy. This study aimed to examine non-structural protein 5A (NS5A) polymorphisms, e.g. IFN/RBV resistance-determining region (IRRDR) and IFN sensitivity-determining region (ISDR), and core protein polymorphism as predictive therapeutic markers. Methods: Pretreatment sequences of NS5A and core regions were analyzed in 68 HCV-1b-infected patients treated with PEG-IFN/RBV. Results: Of 24 patients infected withHCV having an IRRDR with 6 or more mutations (IRRDR≧6), 18 (75%) patients achieved sustained virological response (SVR), whereas only 11 (25%) of 44 patients infected with HCV having IRRDR≤5 did. IRRDR≧6 was significantly associated with SVR (p < 0.0001). On the other hand, ISDR≧2 was significantly associated with relapse (either before [breakthrough] or after end-of-treatment response [ETR[-]relapse]) (p < 0.05) and a point mutation of the core protein from Arg to Gln at position 70 (Gln70) was significantly associated with null-response (p < 0.05). Multivariate analysis identified IRRDR≧6 as the only viral genetic factor that independently predicted SVR. Conclusion: NS5A (IRRDR and ISDR) and core protein polymorphisms are associated with the outcome of PEG-IFN/RBV therapy for chronic hepatitis C. In particular, IRRDR≧6 is a useful marker for prediction of SVR.
© 2011 S. Karger AG, Basel
- Hepatitis C virus
- Non-structural protein 5A
- Interferon/ribavirin resistance-determining region
- Interferon sensitivity-determining region
- Core protein
- Sustained virological response
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Hak Hotta, MD, PhD
Division of Microbiology, Center for Infectious Diseases
Kobe University Graduate School of Medicine
7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan)
Tel. +81 78 382 5500, Fax +81 78 382 5519, E-Mail firstname.lastname@example.org
Received: May 12, 2010
Accepted after revision: October 14, 2010
Published online: February 4, 2011
Number of Print Pages : 11
Number of Figures : 2, Number of Tables : 7, Number of References : 30
Intervirology (International Journal of Basic and Medical Virology)
Vol. 55, No. 1, Year 2012 (Cover Date: November 2011)
Journal Editor: Liebert U.G. (Leipzig)
ISSN: 0300-5526 (Print), eISSN: 1423-0100 (Online)
For additional information: http://www.karger.com/INT
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