scholarly journals Factors Affecting Serum Concentrations of Hepatitis C Virus (HCV) RNA in HCV Genotype 1-Infected Patients with Chronic Hepatitis

2007 ◽  
Vol 45 (8) ◽  
pp. 2426-2433 ◽  
Author(s):  
J. R. Ticehurst ◽  
F. M. Hamzeh ◽  
D. L. Thomas
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Hcv Rna ◽  
Serum Concentrations ◽  
Genotype 1 ◽  
Factors Affecting ◽  
Hcv Genotype ◽  
Hcv Genotype 1

scholarly journals Molecular epidemiology of Hepatitis C Virus (HCV) in liver disease patients in Sri Lanka

2014 ◽  
Vol 6 (3) ◽  
pp. 1-5
Author(s):  
D. B. Senevirathna ◽  
Y. Wahalathanthri ◽  
P. Thiyagarajah ◽  
A. Shani ◽  
S. Jayasinghe ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Liver Disease ◽  
Hepatitis C ◽  
Sri Lanka ◽  
Hcv Rna ◽  
Sri Lankan ◽  
Genotype 1 ◽  
Hcv Genotype ◽  
Specific Amplification ◽  
Hcv Genotype 1

Background: Globally, hepatitis C virus (HCV) is an important cause of chronic liver disease. Genotypes of HCV are associated with different profiles of pathogenicity, infectivity, and antiviral therapy. The prevalence of HCV and distribution of HCV genotypes in Sri Lanka in comparison with the rest of Asia is not well known.Objective: The objective of the study was to investigate the presence of HCV and to genotype HCV in a group of Sri Lankan patients suspected to have liver disease.Methods: A total of 1933 samples were screened for HCV antibodies using ELISA and HCV RNA with RT-PCR methods. RNA positive samples were genotyped by type specific amplification and by DNA sequencing.Results: Out Of the 1933 liver disease patients tested 219 (11.33%) were detected to be positive for anti-HCV antibodies, out of which, 54 (24.66%) were positive for HCV RNA. Furthermore out of 49 positively tested patients, 24 (48.97%) were found to be categorised as HCV genotype 1.Conclusion: This result confirms previous observations that the contribution of HCV as a causative virus in liver disease patients is low in Sri Lanka. HCV genotype 1 was found to be the most predominant genotype in studied cohort of Sri Lankan liver disease patients. DOI: http://dx.doi.org/10.3126/ajms.v6i3.10741Asian Journal of Medical Sciences Vol.6(3) 2015 1-5

scholarly journals Antiviral Effect, Safety, and Pharmacokinetics of Five-Day Oral Administration of Deleobuvir (BI 207127), an Investigational Hepatitis C Virus RNA Polymerase Inhibitor, in Patients with Chronic Hepatitis C

2013 ◽  
Vol 57 (10) ◽  
pp. 4727-4735 ◽  
Author(s):  
Dominique Larrey ◽  
Ansgar W. Lohse ◽  
Christian Trepo ◽  
Jean-Pierre Bronowicki ◽  
Keikawus Arastéh ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Activity ◽  
Rna Polymerase ◽  
Hcv Rna ◽  
Genotype 1 ◽  
Double Blind ◽  
Hcv Genotype ◽  
Hcv Genotype 1 ◽  
Dose Dependent

ABSTRACTDeleobuvir (BI 207127) is an investigational oral nonnucleoside inhibitor of hepatitis C virus (HCV) NS5B RNA polymerase. Antiviral activity, virology, pharmacokinetics, and safety were assessed in HCV genotype 1-infected patients receiving 5 days' deleobuvir monotherapy. In this double-blind phase 1b study, treatment-naive (TN;n= 15) and treatment-experienced (TE;n= 45) patients without cirrhosis received placebo or deleobuvir at 100, 200, 400, 800, or 1,200 mg every 8 h (q8h) for 5 days. Patients with cirrhosis (n= 13) received deleobuvir at 400 or 600 mg q8h for 5 days. Virologic analyses included NS5B genotyping and phenotyping of individual isolates. At day 5, patients without cirrhosis had dose-dependent median HCV RNA reductions of up to 3.8 log10(with no placebo response); patients with cirrhosis had median HCV RNA reductions of approximately 3.0 log10. Three patients discontinued due to adverse events (AEs). The most common AEs were gastrointestinal, nervous system, and skin/cutaneous tissue disorders. Plasma exposure of deleobuvir was supraproportional at doses ≥ 400 mg q8h and approximately 2-fold higher in patients with cirrhosis than in patients without cirrhosis. No virologic breakthrough was observed. NS5B substitutions associated with deleobuvir resistancein vitrowere detected in 9/59 patients; seven encoded P495 substitutions, including P495L, which conferred 120- to 310-fold-decreased sensitivity to deleobuvir. P495 variants did not persist in follow-up without selective drug pressure. Deleobuvir monotherapy was generally well tolerated and demonstrated dose-dependent antiviral activity against HCV genotype 1 over 5 days.

scholarly journals Plasma Ribavirin Trough Concentrations at Week 4 Predict Hepatitis C Virus (HCV) Relapse in HIV-HCV-Coinfected Patients Treated for Chronic Hepatitis C

2010 ◽  
Vol 54 (4) ◽  
pp. 1647-1649 ◽  
Author(s):  
Judit Morello ◽  
Vincent Soriano ◽  
Pablo Barreiro ◽  
José Medrano ◽  
Antonio Madejón ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Odds Ratio ◽  
Hcv Rna ◽  
Genotype 1 ◽  
Baseline Serum ◽  
End Of Treatment ◽  
Trough Concentrations ◽  
Hcv Genotype 1

ABSTRACT The influence of ribavirin trough concentrations (RBV C trough) on the risk of hepatitis C virus (HCV) relapse was retrospectively analyzed in 99 HIV-HCV-coinfected patients who achieved end-of-treatment response with pegylated alpha interferon plus weight-based RBV. The independent predictors (odds ratio [OR] [95% confidence interval (CI)]) of HCV relapse were RBV plasma C trough of <2.5 μg/ml (4.5 [1.3 to 15.5]), baseline serum HCV RNA (2.5 [1.2 to 5.1]), and HCV genotype 1 or 4 (13.3 [2.6 to 66.7]). Monitoring of RBV C trough may permit early adjustment of RBV dosage to avoid HCV relapse.

scholarly journals First-in-Human Study of the Pharmacokinetics and Antiviral Activity of IDX375, a Novel Nonnucleoside Hepatitis C Virus Polymerase Inhibitor

2012 ◽  
Vol 56 (8) ◽  
pp. 4525-4528 ◽  
Author(s):  
J. de Bruijne ◽  
J. van de Wetering de Rooij ◽  
A. A. van Vliet ◽  
X. J. Zhou ◽  
M. F. Temam ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Activity ◽  
Human Study ◽  
Hcv Rna ◽  
Genotype 1 ◽  
Hcv Genotype ◽  
Clinical Investigations ◽  
Hcv Genotype 1 ◽  
Study Participants

ABSTRACTIDX375 is a potent and selective palm-binding nonnucleoside inhibitor of the hepatitis C virus (HCV) genotype 1 polymerase. This first-in-human study evaluated the safety, tolerability, and pharmacokinetics of IDX375 in healthy volunteers, as well as its antiviral activity in HCV-infected patients. IDX375, as a choline salt, was administered for 1 day to 40 healthy male volunteers (25- to 200-mg IDX375-equivalent single ascending doses and a 200-mg twice-daily [BID] dose) and three patients chronically infected with HCV genotype 1 (200 mg BID only). IDX375 was well absorbed and well tolerated by all of the study participants. A single-day 200-mg BID dose resulted in exposure-related anti-HCV activity with maximal 0.5 to 1.1 log10reductions in plasma HCV RNA. These observations support further clinical investigations of IDX375.

scholarly journals In VitroandIn VivoAntiviral Activity and Resistance Profile of Ombitasvir, an Inhibitor of Hepatitis C Virus NS5A

2014 ◽  
Vol 59 (2) ◽  
pp. 979-987 ◽  
Author(s):  
Preethi Krishnan ◽  
Jill Beyer ◽  
Neeta Mistry ◽  
Gennadiy Koev ◽  
Thomas Reisch ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Wild Type Virus ◽  
Hcv Rna ◽  
Sequencing Analysis ◽  
Genotype 1 ◽  
Resistant Variant ◽  
Hcv Genotype ◽  
Hcv Genotype 1

ABSTRACTOmbitasvir (ABT-267) is a hepatitis C virus (HCV) NS5A inhibitor with picomolar potency, pan-genotypic activity, and 50% effective concentrations (EC50s) of 0.82 to 19.3 pM against HCV genotypes 1 to 5 and 366 pM against genotype 6a. Ombitasvir retained these levels of potency against a panel of 69 genotype 1 to 6 chimeric replicons containing the NS5A gene derived from HCV-infected patients, despite the existence of natural sequence diversity within NS5A.In vitroresistance selection identified variants that conferred resistance to ombitasvir in the HCV NS5A gene at amino acid positions 28, 30, 31, 58, and 93 in genotypes 1 to 6. Ombitasvir was evaluatedin vivoin a 3-day monotherapy study in 12 HCV genotype 1-infected patients at 5, 25, 50, or 200 mg dosed once daily. All patients in the study were HCV genotype 1a infected and were without preexisting resistant variants at baseline as determined by clonal sequencing. Decreases in HCV RNA up to 3.1 log10IU/ml were observed. Resistance-associated variants at position 28, 30, or 93 in NS5A were detected in patient samples 48 hours after the first dose. Clonal sequencing analysis indicated that wild-type virus was largely suppressed by ombitasvir during 3-day monotherapy, and at doses higher than 5 mg, resistant variant M28V was also suppressed. Ombitasvir was well tolerated at all doses, and there were no serious or severe adverse events. These data support clinical development of ombitasvir in combination with inhibitors targeting HCV NS3/4A protease (ABT-450 with ritonavir) and HCV NS5B polymerase (ABT-333, dasabuvir) for the treatment of chronic HCV genotype 1 infection. (Study M12-116 is registered at ClinicalTrials.gov under registration no. NCT01181427.)

scholarly journals Quantification of Hepatitis C Virus (HCV) RNA in a Multicenter Study: Implications for Management of HCV Genotype 1-Infected Patients

2009 ◽  
Vol 47 (9) ◽  
pp. 2931-2936 ◽  
Author(s):  
G. Pisani ◽  
K. Cristiano ◽  
F. Marino ◽  
F. Luciani ◽  
G. M. Bisso ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Multicenter Study ◽  
Hcv Rna ◽  
Genotype 1 ◽  
Hcv Genotype ◽  
Hcv Genotype 1

scholarly journals Quantification of Hepatitis C Virus (HCV) RNA in a Multicenter Study: Implications for Management of HCV Genotype 1-Infected Patients

2009 ◽  
Vol 47 (11) ◽  
pp. 3795-3795
Author(s):  
G. Pisani ◽  
K. Cristiano ◽  
F. Marino ◽  
F. Luciani ◽  
G. M. Bisso ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Multicenter Study ◽  
Hcv Rna ◽  
Genotype 1 ◽  
Hcv Genotype ◽  
Hcv Genotype 1

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 Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of GSK2336805, an Inhibitor of Hepatitis C Virus (HCV) NS5A, in Healthy Subjects and Subjects Chronically Infected with HCV Genotype 1

2013 ◽  
Vol 57 (10) ◽  
pp. 5037-5044 ◽  
Author(s):  
D. A. Wilfret ◽  
J. Walker ◽  
K. K. Adkison ◽  
L. A. Jones ◽  
Y. Lou ◽  
...  
Keyword(s):  
Single Dose ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Activity ◽  
Healthy Subjects ◽  
Hcv Rna ◽  
Genotype 1 ◽  
Once Daily ◽  
Hcv Genotype ◽  
Hcv Genotype 1

ABSTRACTGSK2336805 is an orally bioavailable hepatitis C virus (HCV) inhibitor working through an NS5A-mediated mechanism. This first-time-in-human study was conducted to assess the safety, tolerability, pharmacokinetics, metabolism, and efficacy of GSK2336805 in healthy subjects and subjects infected with HCV genotype 1. We performed a three-part, randomized, double-blind, placebo-controlled study in 46 healthy subjects and 23 HCV-infected subjects. After an overnight fast, healthy subjects received GSK2336805 as 10 mg, 30 mg, 30 mg plus food, and 60 mg in a single dose and 10 mg (7 days), 30 mg (7 days), and 75 mg (14 days) in a once-daily multiple dose. Subjects with HCV received GSK2336805 as a 1- to 120-mg single dose. In subjects with HCV, reductions in HCV RNA were observed within 4 h and a single dose of GSK2336805 of ≥10 mg resulted in a statistically significant ≥2-log reduction in HCV RNA compared with placebo at 24 h postdose. GSK2336805 was readily absorbed in all subjects, and the half-life (t1/2) was suitable for once-daily dosing. Administration of GSK2336805 with food had no effect on plasma GSK2336805 exposure; however, absorption was delayed, with a mediantmax(time to maximum concentration of drug in serum) of 4.5 versus 2.0 h. Twenty subjects who received GSK2336805 experienced mild to moderate adverse events; none were serious. GSK2336805 was well tolerated and exhibited rapid, significant antiviral activity after a single dose in HCV-infected subjects. These results support the conduct of further studies evaluating GSK2336805 administered once daily for longer durations in combination with peginterferon, ribavirin, and other direct-acting antivirals. (This study has been registered at ClinicalTrials.gov under registration no. NCT01277692.)

scholarly journals Bile Acids Promote the Expression of Hepatitis C Virus in Replicon-Harboring Cells

2007 ◽  
Vol 81 (18) ◽  
pp. 9633-9640 ◽  
Author(s):  
Kyeong-Ok Chang ◽  
David W. George
Keyword(s):  
Hepatitis C Virus ◽  
Bile Acid ◽  
Hepatitis C ◽  
Bile Acids ◽  
Farnesoid X Receptor ◽  
Hcv Rna ◽  
Genotype 1 ◽  
Hcv Genotype ◽  
Hcv Genotype 1 ◽  
Chronic Hcv

ABSTRACT Hepatitis C virus (HCV) is a cause of chronic liver disease, with more than 170 million persistently infected individuals worldwide. Although the combination therapy of alpha interferon (IFN-α) and ribavirin is effective for chronic HCV infection, around half of all patients infected with HCV genotype 1 fail to show sustained virologic responses and remain chronically infected. Previously, we demonstrated that bile acids were essential for growth of porcine enteric calicivirus in cell culture in association with down-regulation of IFN responses. Because hepatocytes are exposed to high concentrations of bile acids in the liver, we hypothesized that bile acids have similar effects on HCV replication. We incubated HCV replicon-harboring cells (genotype 1b, Con1) in the presence of various bile acids and monitored the expression of HCV RNA and protein (NS5B). The addition of an individual bile acid (deoxycholic acid, chenodeoxycholic acid, ursodeoxycholic acid, or glycochenodeoxycholic acid) in the medium increased the levels of HCV RNA and proteins up to fivefold at 48 h of incubation. An antagonist of bile acid receptor farnesoid X receptor (FXR), Z-guggulsterone, reduced the bile acid-mediated increase of HCV RNA. When IFN (α or γ) and each bile acid were incubated together, we observed that bile acid significantly reduced the anti-HCV effect of IFN. These results indicated that bile acids are factors in the failure of IFN treatment for certain patients infected with HCV genotype 1. Our finding may also contribute to the establishment of better regimens for treatment of chronic HCV infections by including agents altering the bile acid-mediated FXR pathway.

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