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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
NS5A sequence heterogeneity of hepatitis C virus genotype 4a predicts clinical outcome of pegylated-interferon-ribavirin therapy in Egyptian patients
Journal of Clinical Microbiology, Volume 50, No. 12, Year 2012
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Description
Hepatitis C virus genotype 4 (HCV-4) is the cause of approximately 20% of the 180 million cases of chronic hepatitis C in the world. HCV-4 infection is common in the Middle East and Africa, with an extraordinarily high prevalence in Egypt. Viral genetic polymorphisms, especially within core and NS5A regions, have been implicated in influencing the response to pegylated-interferon and ribavirin (PEG-IFN/RBV) combination therapy in HCV-1 infection. However, this has not been confirmed in HCV-4 infection. Here, we investigated the impact of heterogeneity of NS5A and core proteins of HCV-4, mostly subtype HCV-4a, on the clinical outcomes of 43 Egyptian patients treated with PEG-IFN/RBV. Sliding window analysis over the carboxy terminus of NS5A protein identified the IFN/RBV resistance-determining region (IRRDR) as the most prominent region associated with sustained virological response (SVR). Indeed, 21 (84%) of 25 patients with SVR, but only 5 (28%) of 18 patients with non-SVR, were infected with HCV having IRRDR with 4 or more mutations (IRRDR ≥ 4) (P = 0.0004). Multivariate analysis identified IRRDR ≥ 4 as an independent SVR predictor. The positive predictive value of IRRDR ≥ 4 for SVR was 81% (21/26; P = 0.002), while its negative predictive value for non-SVR was 76% (13/17; P = 0.02). On the other hand, there was no significant correlation between core protein polymorphisms, either at residue 70 or at residue 91, and treatment outcome. In conclusion, the present results demonstrate for the first time that IRRDR ≥ 4, a viral genetic heterogeneity, would be a useful predictive marker for SVR in HCV-4 infection when treated with PEG-IFN/RBV. Copyright © 2012, American Society for Microbiology. All Rights Reserved.
Authors & Co-Authors
El-Shamy, Ahmed M.
Japan, Kobe
Graduate School of Medicine
Egypt, Ismailia
Faculty of Veterinary Medicine
United States, New York
Icahn School of Medicine at Mount Sinai
Shoji, Ikuo
Japan, Kobe
Graduate School of Medicine
Elakel, Wafaa Ahmed
Egypt, Giza
Cairo University
Bilasy, Shymaa El Shawadfy
Egypt, Ismailia
Faculty of Pharmacy
Deng, Lin
Japan, Kobe
Graduate School of Medicine
El-Raziky, Maissa S.
Egypt, Giza
Cairo University
Jiang, Dapeng
Japan, Kobe
Graduate School of Medicine
Esmat, Gamal
Egypt, Giza
Cairo University
Hotta, Haku
Japan, Kobe
Graduate School of Medicine
Statistics
Citations: 25
Authors: 9
Affiliations: 5
Identifiers
Doi:
10.1128/JCM.02109-12
ISSN:
00951137
e-ISSN:
1098660X
Research Areas
Genetics And Genomics
Infectious Diseases
Study Design
Cross Sectional Study
Study Locations
Egypt