Role of hepatitis C virus substitutions and interleukin-28B polymorphism on response to peginterferon plus ribavirin in a prospective study of response-guided therapy
Summary Recent studies have indicated that amino acid (aa) substitutions in the core region and NS5A interferon sensitivity‐determining region (ISDR) of hepatitis C virus (HCV) as well as genetic polymorphisms in the interleukin‐28B (IL‐28B) locus affect the outcome of interferon (IFN)‐based therapi...
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Published in | Journal of viral hepatitis Vol. 20; no. 11; pp. 761 - 769 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
Blackwell Publishing Ltd
01.11.2013
Wiley Subscription Services, Inc |
Subjects | |
Online Access | Get full text |
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Summary: | Summary
Recent studies have indicated that amino acid (aa) substitutions in the core region and NS5A interferon sensitivity‐determining region (ISDR) of hepatitis C virus (HCV) as well as genetic polymorphisms in the interleukin‐28B (IL‐28B) locus affect the outcome of interferon (IFN)‐based therapies. We aimed to investigate the role of these factors on response to peginterferon plus ribavirin in a prospective study of response‐guided therapy. The aa sequences in core region and ISDR and rs12979860 genotypes were analysed in 115 HCV‐1 patients. The treatment was 24 weeks for patients achieving a rapid virological response (RVR), 48 weeks for those with an early virological response (EVR) and early terminated in those without an EVR. A sustained virological response (SVR) was achieved in 82% of 34 RVR patients, 45% of 74 EVR patients and 0% of seven non‐EVR patients. Logistic regression analysis showed that ISDR mutation (≥2) [odds ratio(OR): 6.024], double core 70/91 mutations (OR: 0.136), and platelet counts ≥ 15 × 104/μL (OR: 3.119) were independent pretreatment factors associated with SVR. Apart from rs12979860 CC genotype, low viral load and ISDR mutation (≥2) were significant factors predictive of RVR. Combination of rs12979860 genotype and baseline viral characteristics (viral load and core/ISDR mutations) could predict RVR and SVR with positive predictive value of 100% and 91%, and negative predictive value of 80% and 54%, respectively. In conclusion, pretreatment screening rs12979860 genotype and aa substitutions in the core region and ISDR could help identifying patients who are good candidates for peginterferon plus ribavirin therapy. |
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Bibliography: | ArticleID:JVH12097 ark:/67375/WNG-273JSP8C-1 istex:9622B10C63D69DA3374E4B11BC0AB96335074AC0 Table S1: Analysis of factors associated with non-early virological response. Chang Gung Memorial Hospital ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 |
ISSN: | 1352-0504 1365-2893 |
DOI: | 10.1111/jvh.12097 |