scholarly journals Mutations in E2-PePHD, NS5A-PKRBD, NS5A-ISDR, and NS5A-V3 of Hepatitis C Virus Genotype 1 and Their Relationships to Pegylated Interferon-Ribavirin Treatment Responses

2008 ◽  
Vol 82 (13) ◽  
pp. 6644-6653 ◽  
Author(s):  
P. Muñoz de Rueda ◽  
J. Casado ◽  
R. Patón ◽  
D. Quintero ◽  
A. Palacios ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Genetic Variability ◽  
Variable Region ◽  
Pegylated Interferon ◽  
Genotype 1 ◽  
Serum Samples ◽  
Virus Genotype ◽  
Hcv Genotype ◽  
Hcv Genotype 1

ABSTRACT Mutations in several subgenomic regions of hepatitis C virus (HCV) have been implicated in influencing the response to interferon (IFN) therapy. Sequences within HCV NS5A (PKR binding domain [PKRBD], IFN sensitivity-determining region [ISDR], and variable region 3 [V3]) were analyzed for the pretreatment serum samples of 60 HCV genotype 1-infected patients treated with pegylated IFN plus ribavirin (1b, n = 47; 1a, n = 13) but with different treatment outcomes, those with sustained virologic responses (SVR; n = 36) or nonresponders (NR; n = 24). Additionally, the sequence of the PKR/eIF-2α phosphorylation homology domain (E2-PePHD) region was determined for 23 patients (11 SVR and 12 NR). The presence of >4 mutations in the PKRBD region was associated with SVR (P = 0.001) and early virologic responses (EVR; 12 weeks) (P = 0.037) but not rapid virologic responses (4 weeks). In the ISDR, the difference was almost statistically significant (68% of SVR patients with mutations versus 45% without mutations; P = 0.07). The V3 region had a very high genetic variability, but this was not related to SVR. Finally, the E2-PePHD (n = 23) region was well conserved. The presence of >4 mutations in the PKRBD region (odds ratio [OR] = 9.9; P = 0.006) and an age of ≤40 years (OR = 3.2; P = 0.056) were selected in a multivariate analysis as predictive factors of SVR. NS5A sequences from serum samples taken after 1 month of treatment and posttreatment were examined for 3 SVR and 15 NR patients to select treatment-resistant viral subpopulations, and it was found that in the V3 and flanking regions, the mutations increased significantly in posttreatment sera (P = 0.05). The genetic variability in the PKRBD (>4 mutations) is a predictive factor of SVR and EVR in HCV genotype 1 patients treated with pegylated IFN and ribavirin.

scholarly journals In VitroActivity of BMS-790052 on Hepatitis C Virus Genotype 4 NS5A

2011 ◽  
Vol 56 (3) ◽  
pp. 1588-1590 ◽  
Author(s):  
Chunfu Wang ◽  
Lingling Jia ◽  
Haichang Huang ◽  
Dike Qiu ◽  
Lourdes Valera ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Nonstructural Protein ◽  
Genotype 1 ◽  
Virus Genotype ◽  
Valuable Component ◽  
Genotype 4 ◽  
Replication Complex ◽  
Hcv Genotype ◽  
Hcv Genotype 1

ABSTRACTThe antiviral profile of BMS-790052, a potent hepatitis C virus (HCV) replication complex inhibitor targeting nonstructural protein NS5A, is well characterized for HCV genotype-1. Here, we report that BMS-790052 inhibits hybrid replicons containing HCV genotype-4 NS5A genes with 50% effective concentrations (EC50s) ranging from 7 to 13 pM. NS5A residue 30 was an important site for BMS-790052-selected resistance in the hybrid replicons. Our results support the potential of BMS-790052 as a valuable component of combination therapy for HCV genotype-4 chronic infection.

Hepatitis C virus genotype 1: How genetic variability of the core protein affects the response to pegylated-interferon and ribavirin therapy

2013 ◽  
Vol 86 (2) ◽  
pp. 224-234 ◽  
Author(s):  
F.S. Alhamlan ◽  
M.N. Al-Ahdal ◽  
N.Z. Khalaf ◽  
A.A. Abdo ◽  
F.M. Sanai ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Genetic Variability ◽  
Core Protein ◽  
Pegylated Interferon ◽  
Genotype 1 ◽  
Virus Genotype ◽  
The Core

scholarly journals Optimizing Hepatitis C Therapy in HIV/hepatitis C Virus (HCV) Coinfected Patients: Analysis of HCV Viral Kinetics on Treatment

2012 ◽  
Vol 23 (1) ◽  
pp. 31-35 ◽  
Author(s):  
Paul Damien James ◽  
David KH Wong
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Pegylated Interferon ◽  
Hcv Rna ◽  
Genotype 1 ◽  
Viral Kinetics ◽  
Hcv Genotype ◽  
Hiv Coinfection ◽  
Genotype 2 ◽  
Hcv Genotype 1

INTRODUCTION: Hepatitis C virus (HCV) infection is potentially curable, but the sustained virological response (SVR) has been shown to be lower in patients coinfected HIV. A single-centre experience treating individuals with HCV and HIV coinfection is reported.METHODS: Twenty-one patients who received standard doses of pegylated interferon with weight-based dosing of ribavirin (mean 14.3 mg/kg) were retrospectively reviewed. Qualitative HCV polymerase chain reaction (PCR) was performed prospectively every four weeks if the patient remained HCV PCR positive. All patients with HCV genotype 1 were treated for 48 weeks. Patients with genotype 2 or 3 were treated for 24 weeks and 32 weeks to 36 weeks if their HCV RNA level was undetectable after four weeks (RVR4) or eight weeks (RVR8) of therapy, respectively. If RVR8 was not achieved, the treatment was continued for 48 weeks.RESULTS: There were no dropouts or dose reductions within the first 12 weeks of treatment. SVR status was available for 20 patients and adequate serum for viral kinetics analyses was available for 17 patients. Eighty per cent of the patients achieved SVR (50% genotype 1; 100% genotypes 2 and 3). The week 8 viral load remained elevated for all genotype 1 nonresponders.DISCUSSION: High effectiveness rates were seen, particularly in patients with HCV genotype 2 and 3 who were treated for shorter durations. HCV viral loads after eight weeks of therapy helped distinguish patients with HCV genotype 1 who would respond to therapy.

scholarly journals Effects of 12-week treatment with Sovodak in patients infected by genotype 1 hepatitis C virus

2019 ◽  
Vol 7 (1) ◽  
pp. 1-6
Author(s):  
Hosein Mehdipour ◽  
Yaghoub Moaddab ◽  
Khalil Azizian ◽  
Morteza Ghojazadeh ◽  
Mohammad Hossein Somi
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
High Rate ◽  
Genotype 1 ◽  
Hcv Genotype ◽  
Definitive Evidence ◽  
Single Pill ◽  
Treatment Naïve ◽  
Hcv Genotype 1 ◽  
Rate Of Success

Introduction: It has been shown that the combination therapy of Sofosbuvir-Daclatasvir (Sof/Dac) has a high rate of success in the treatment of patients. For the first time, a single pill of Sof/Dac has been formulated in Iran (Sovodak). In this regard, the present study was carried out aiming to investigate the safety and efficacy of Sovodak for 12 weeks during treatment of patients infected by genotype 1 hepatitis C virus (HCV). Methods: In this study, 50 patients (25 and 25 treatment-naïve and treatment-experienced patients, respectively) infected by HCV genotype 1 received Sovodak (1pill per day) for 12 weeks. Ribavirin was added for patients who had definitive evidence of liver cirrhosis. The sustained virological response (SVR12) was investigated 12 weeks after the end of the therapy. Results: All 50 patients completed the treatment period. The mean age of patients was 54.40 ± 11.69 years, in addition, 60% and 90% of the patients were male and infected by HCV genotype 1b, respectively. After 4 and 12 weeks of treatment with Sovodak, the HCV ribonucleic acid (RNA) titer was undetectable in 82% and 100 % of the patients, respectively and 100% of them achieved SVR12. None of the subjects reported treatment discontinuation because of adverse events, however, 3 patients reported transient side effects including foot swelling, headache, and vomiting. Conclusion: The results of this study showed that once-daily Sovodak single-pill for 12 weeks is an effective and safe medicine for treating patients infected by HCV genotype 1

scholarly journals In VitroActivity and Resistance Profile of Dasabuvir, a Nonnucleoside Hepatitis C Virus Polymerase Inhibitor

2014 ◽  
Vol 59 (3) ◽  
pp. 1505-1511 ◽  
Author(s):  
Warren Kati ◽  
Gennadiy Koev ◽  
Michelle Irvin ◽  
Jill Beyer ◽  
Yaya Liu ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Clinical Isolates ◽  
Genotype 1 ◽  
Subgenomic Replicon ◽  
Hcv Genotype ◽  
Genotype 1A ◽  
Treatment Naïve ◽  
Hcv Genotype 1 ◽  
Hcv Ns5b

ABSTRACTDasabuvir (ABT-333) is a nonnucleoside inhibitor of the RNA-dependent RNA polymerase encoded by the hepatitis C virus (HCV) NS5B gene. Dasabuvir inhibited recombinant NS5B polymerases derived from HCV genotype 1a and 1b clinical isolates, with 50% inhibitory concentration (IC50) values between 2.2 and 10.7 nM, and was at least 7,000-fold selective for the inhibition of HCV genotype 1 polymerases over human/mammalian polymerases. In the HCV subgenomic replicon system, dasabuvir inhibited genotype 1a (strain H77) and 1b (strain Con1) replicons with 50% effective concentration (EC50) values of 7.7 and 1.8 nM, respectively, with a 13-fold decrease in inhibitory activity in the presence of 40% human plasma. This level of activity was retained against a panel of chimeric subgenomic replicons that contained HCV NS5B genes from 22 genotype 1 clinical isolates from treatment-naive patients, with EC50s ranging between 0.15 and 8.57 nM. Maintenance of replicon-containing cells in medium containing dasabuvir at concentrations 10-fold or 100-fold greater than the EC50resulted in selection of resistant replicon clones. Sequencing of the NS5B coding regions from these clones revealed the presence of variants, including C316Y, M414T, Y448C, Y448H, and S556G, that are consistent with binding to the palm I site of HCV polymerase. Consequently, dasabuvir retained full activity against replicons known to confer resistance to other polymerase inhibitors, including the S282T variant in the nucleoside binding site and the M423T, P495A, P495S, and V499A single variants in the thumb domain. The use of dasabuvir in combination with inhibitors targeting HCV NS3/NS4A protease (ABT-450 with ritonavir) and NS5A (ombitasvir) is in development for the treatment of HCV genotype 1 infections.

scholarly journals Reliable resolution of ambiguous hepatitis C virus genotype 1 results with the Abbott HCV Genotype Plus RUO assay

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
V. Saludes ◽  
A. Antuori ◽  
B. Reinhardt ◽  
I. Viciana ◽  
E. Clavijo ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Genotype 1 ◽  
Virus Genotype ◽  
Hcv Genotype
Sign in / Sign up

Export Citation Format

Share Document