Dataset Information

Prevalence of hepatitis C virus (HCV) variants resistant to NS5A inhibitors in naive patients infected with HCV genotype 1 in Tunisia.

ABSTRACT: Hepatitis C virus (HCV) non-structural protein 5A (NS5A) inhibitors have been recently developed to inhibit NS5A activities and have been approved for the treatment of HCV infection. However the drawback of these direct acting antivirals (DAAs) is the emergence of resistance mutations. The prevalence of such mutations conferring resistance to HCV-NS5A inhibitors before treatment has not been investigated so far in the Tunisian population. The aim of this study was to detect HCV variants resistant to HCV-NS5A inhibitors in hepatitis C patients infected with HCV genotype 1 before any treatment with NS5A inhibitors.Amplification and direct sequencing of the HCV NS5A region was carried out on 112 samples from 149 untreated patients.In genotype 1a strains, amino acid substitutions conferring resistance to NS5A inhibitors (M28V) were detected in 1/7 (14.2 %) HCV NS5A sequences analyzed. In genotype 1b, resistance mutations in the NS5A region (R30Q; L31M; P58S and Y93H) were observed in 17/105 (16.2 %) HCV NS5A sequences analyzed. R30Q and Y93H (n?=?6; 5.7 %) predominated over P58S (n?=?4; 3.8 %) and L31M (n?=?3; 2.8 %).Mutations conferring resistance to HCV NS5A inhibitors are frequent in treatment-naïve Tunisian patients infected with HCV genotype 1b. Their influence in the context of DAA therapies has not been fully investigated and should be taken into consideration.

SUBMITTER: Aissa Larousse J

PROVIDER: S-EPMC4465297 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Prevalence of hepatitis C virus (HCV) variants resistant to NS5A inhibitors in naïve patients infected with HCV genotype 1 in Tunisia.

Aissa Larousse Jameleddine J Trimoulet Pascale P Recordon Pinson Patricia P Tauzin Brigitte B Azzouz Mohamed Mssadak MM Ben Mami Nabyl N Cheikh Imed I Triki Henda H Fleury Hervé H

Virology journal 20150606

<h4>Background</h4>Hepatitis C virus (HCV) non-structural protein 5A (NS5A) inhibitors have been recently developed to inhibit NS5A activities and have been approved for the treatment of HCV infection. However the drawback of these direct acting antivirals (DAAs) is the emergence of resistance mutations. The prevalence of such mutations conferring resistance to HCV-NS5A inhibitors before treatment has not been investigated so far in the Tunisian population. The aim of this study was to detect HC ...[more]

PMID: 26047611

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Project description:Renal transplantation from hepatitis C (HCV) nucleic acid amplification test-positive (NAAT-positive) donors to uninfected recipients has greatly increased the organ donation pool. However, there is concern for adverse outcomes in these recipients due to dysregulated immunologic activation secondary to active inflammation from acute viremia at the time of transplantation. This includes increased rates of cytomegalovirus (CMV) DNAemia and allograft rejection. In this study, we evaluate transcriptional responses in circulating leukocytes to define the character, timing, and resolution of this immune dysregulation and assess for biomarkers of adverse outcomes in transplant patients. We enrolled 67 renal transplant recipients (30 controls, 37 HCV recipients) and performed RNA sequencing on serial samples from one, 3-, and 6-months post-transplant. CMV DNAemia and allograft rejection outcomes were measured. Least absolute shrinkage and selection operator was utilized to develop gene expression classifiers predictive of clinical outcomes. Acute HCV incited a marked transcriptomic response in circulating leukocytes of renal transplant recipients in the acute post-transplant setting, despite the presence of immunosuppression, with 109 genes significantly differentially expressed compared to controls. These HCV infection-associated genes were reflective of antiviral immune pathways and generally resolved by the 3-month timepoint after sustained viral response (SVR) for HCV. Differential gene expression was also noted from patients who developed CMV DNAemia or allograft rejection compared to those who did not, although transcriptomic classifiers could not accurately predict these outcomes, likely due to sample size and variable time-to-event. Acute HCV infection incites evidence of immune activation and canonical antiviral responses in the human host even in the presence of systemic immunosuppression. After treatment of HCV with antiviral therapy and subsequent aviremia, this immune activation resolves. Changes in gene expression patterns in circulating leukocytes are associated with some clinical outcomes, although larger studies are needed to develop accurate predictive classifiers of these events.

Dataset Information

Prevalence of hepatitis C virus (HCV) variants resistant to NS5A inhibitors in naive patients infected with HCV genotype 1 in Tunisia.

Publications

Prevalence of hepatitis C virus (HCV) variants resistant to NS5A inhibitors in naïve patients infected with HCV genotype 1 in Tunisia.

Similar Datasets

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