Dataset Information

Evolution of viral RNA in a Chinese patient to interferon/ribavirin therapy for hepatitis C.

ABSTRACT: OBJECTIVE:The combination of interferon (IFN) and ribavirin (RBV) is the standard therapy for hepatitis C virus (HCV) infection. HCV genotype 2a has proved more amenable to the therapy, but its efficacy is yet limited. This study aimed to investigate the mechanism of the poor response in a case of HCV genotype 2a infection. METHODS:We analyzed dynamic change of HCV RNA from a patient, infected with HCV genotype 2a, showing a poor virological response to IFN/RBV as judged 12 weeks after initiation of the therapy by HCV clone sequencing. Then we constructed subgenomic Japanese fulminant hepatitis-1 (JFH1) replicon and different chimeric replicons with humanized Gaussia luciferase gene. The chimeric replicons were derived from subgenomic JFH1 replicon, in which the NS5A region was replaced by the patient's sequence from the pre/post-treatment, and the chimeric replicons' susceptibility to IFN were evaluated by relative Gausia Luciferase activity. RESULTS:The pretreatment HCV sequences appeared almost uniform, and the quasispecies variation was further more simplified after 12 weeks of therapy. Besides, the quasispecies variation seemed to be more diversified in the NS5A, relatively, a region crucial for IFN response, and each of chimeric replicons exhibited distinct response to IFN. CONCLUSIONS:During the course of the chronic infection, HCV population seems to be adapted to the patient's immunological system, and further to be selected by combination of IFN/RBV therapy, indicating quasispecies may completely eliminated by addition of other drugs with targets different from those of IFN. In addition, each different response of chimeric replicon to IFN is most likely related to amino acid changes in or near the IFN-sensitivity determining region (ISDR) of NS5A during chronic infection and IFN/RBV therapy.

SUBMITTER: Wen XZ

PROVIDER: S-EPMC3551335 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Evolution of viral RNA in a Chinese patient to interferon/ribavirin therapy for hepatitis C.

Wen Xian-Zi XZ Chen Zhi-Hai ZH Wei Ya-Zhi YZ Ji Jia-Fu JF

Chinese journal of cancer research = Chung-kuo yen cheng yen chiu 20121201 4

<h4>Objective</h4>The combination of interferon (IFN) and ribavirin (RBV) is the standard therapy for hepatitis C virus (HCV) infection. HCV genotype 2a has proved more amenable to the therapy, but its efficacy is yet limited. This study aimed to investigate the mechanism of the poor response in a case of HCV genotype 2a infection.<h4>Methods</h4>We analyzed dynamic change of HCV RNA from a patient, infected with HCV genotype 2a, showing a poor virological response to IFN/RBV as judged 12 weeks ...[more]

PMID: 23359634

Similar Datasets

Project description:BACKGROUND:The standard treatment for patients with chronic hepatitis C (CHC), pegylated interferon-? (PEG-IFN) plus ribavirin (RBV) does not provide a sustained virological response (SVR) in all patients. Genetic variations at the interleukin 28B (IL-28B) locus are important in predicting outcome following therapy in CHC patients. RESULTS:We investigated the role of IL28B variations (rs8099917) in response to PEG-IFN-?/RBV treatment and evaluated its association with the risk of the null virological response (NVR) and relapse (REL) in different viral genotypes. We found that the overall distributions of the genotype among the SVR, NVR, and REL groups were significantly different (P < 0.001). Patients with the TG genotype had an increased risk of NVR and REL (OR = 6.45 95% CI = 2.88-14.47, P < 0.001 for NVR; OR = 2.51, 95% CI = 1.29-4.86, P = 0.006 for REL, respectively), and patients with the GG genotype had a further increased risk of NVR and REL (OR = 12.04, 95% CI = 3.21-45.13, P < 0.001 for NVR; ,OR = 4.30, 95% CI = 1.21-15.13, P = 0.017 for REL, respectively). G variant genotypes (TG+GG) also had an increased risk of NVR and REL, and there was a significant trend for a dose-effect of G allele on the risk of NVR and REL (P < 0.05). The SVR rate in TT higher than in TG+GG was more pronounced in those patients infected with non-G1 compared to the patients infected with G1. The treatment response did differ based on the rs8099917 genotype in patients with different viral genotypes, compared with patients infected with the non-G1, the G1 infected patients had an increased risk of NVR and REL (OR = 2.03 95% CI = 1.03-4.01, P = 0.04 for NVR and OR = 2.58, 95% CI = 1.35-4.94, P = 0.004 for REL, respectively). Moreover, multivariate regression analysis show that the rs8099917 G allele was the only independent factor significantly associated with a NVR and REL. CONCLUSION:This study suggests that host genetic polymorphisms rs8099917 in the vicinity of IL-28B is the most important predictor of treatment response of PEG-IFN-?/RBV for HCV patients in China.

Dataset Information

Evolution of viral RNA in a Chinese patient to interferon/ribavirin therapy for hepatitis C.

Publications

Evolution of viral RNA in a Chinese patient to interferon/ribavirin therapy for hepatitis C.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets