Hepatitis C Virus (HCV) Genotype Assay (LiPA)

Author(s):  
Charles E. Stager ◽  
Tavat A. Buraruk
2012 ◽  
Vol 56 (7) ◽  
pp. 3670-3681 ◽  
Author(s):  
Fiona McPhee ◽  
Jacques Friborg ◽  
Steven Levine ◽  
Chaoqun Chen ◽  
Paul Falk ◽  
...  

ABSTRACTAsunaprevir (BMS-650032) is a potent hepatitis C virus (HCV) NS3 protease inhibitor demonstrating efficacy in alfa interferon-sparing, direct-acting antiviral dual-combination regimens (together with the NS5A replication complex inhibitor daclatasvir) in patients chronically infected with HCV genotype 1b. Here, we describe a comprehensivein vitrogenotypic and phenotypic analysis of asunaprevir-associated resistance against genotypes 1a and 1b using HCV replicons and patient samples obtained from clinical studies of short-term asunaprevir monotherapy. During genotype 1a resistance selection using HCV replicons, the primary NS3 protease substitutions identified were R155K, D168G, and I170T, which conferred low- to moderate-level asunaprevir resistance (5- to 21-fold) in transient-transfection susceptibility assays. For genotype 1b, a higher level of asunaprevir-associated resistance was observed at the same selection pressures, ranging from 170- to 400-fold relative to the wild-type control. The primary NS3 protease substitutions identified occurred predominantly at amino acid residue D168 (D168A/G/H/V/Y) and were associated with high-level asunaprevir resistance (16- to 280-fold) and impaired replication capacity. In asunaprevir single-ascending-dose and 3-day multiple-ascending-dose studies in HCV genotype 1a- or 1b-infected patients, the predominant pre-existing NS3 baseline polymorphism was NS3-Q80K. This substitution impacted initial virologic response rates in a single-ascending-dose study, but its effects after multiple doses were more ambiguous. Interestingly, for patient NS3 protease sequences containing Q80 and those containing K80, susceptibilities to asunaprevir were comparable when tested in an enzyme assay. No resistance-associated variants emerged in these clinical studies that significantly impacted susceptibility to asunaprevir. Importantly, asunaprevir-resistant replicons remained susceptible to an NS5A replication complex inhibitor, consistent with a role for asunaprevir in combination therapies.


2006 ◽  
Vol 196 (1) ◽  
pp. 11-21 ◽  
Author(s):  
Ankur Goyal ◽  
Wolf P. Hofmann ◽  
Eva Hermann ◽  
Stella Traver ◽  
Syed S. Hissar ◽  
...  

2009 ◽  
Vol 51 (6) ◽  
pp. 325-329 ◽  
Author(s):  
Daniela Fernandes Cardoso ◽  
Fernando Vieira de Souza ◽  
Luiz Augusto M. Fonseca ◽  
Alberto José da Silva Duarte ◽  
Jorge Casseb

Hepatitis C virus (HCV) and human T-cell lymphotropic virus type 1 (HTLV-1) share routes of transmission and some individuals have dual infection. Although some studies point to a worse prognosis of hepatitis C virus in patients co-infected with HTLV-1, the interaction between these two infections is poorly understood. This study evaluated the influence of HTLV-1 infection on laboratory parameters in chronic HCV patients. Twelve HTLV-1/HCV-coinfected patients were compared to 23 patients infected only with HCV, in regard to demographic data, risk factors for viral acquisition, HCV genotype, presence of cirrhosis, T CD4+ and CD8+ cell counts and liver function tests. There was no difference in regard to age, gender, alcohol consumption, smoking habits, HCV genotype or presence of cirrhosis between the groups. Intravenous drug use was the most common risk factor among individuals co-infected with HTLV-1. These patients showed higher TCD8+ counts (p = 0.0159) and significantly lower median values of AST and ALT (p = 0.0437 and 0.0159, respectively). In conclusion, we have shown that HCV/HTLV-1 co-infected patients differs in laboratorial parameters involving both liver and immunological patterns. The meaning of these interactions in the natural history of these infections is a matter that deserves further studies.


2019 ◽  
Vol 49 ◽  
Author(s):  
Irma Salimović- Bešić ◽  
Adna Kahriman ◽  
Suzana Arapčić ◽  
Amela Dedeić- Ljubović

Background: Hepatitis C virus (HCV) genotypes and subtypes exhibit significant geographic variations.Aim: To analyse the distribution of genotypes/subtypes of HCV in a group of patients with chronic hepatitis C from Canton Sarajevo during 2012-2018.Material and methods:The study enrolled 247 human plasma samples of HCV-RNA positive patients with available results of HCV genotyping test.Results: During 2012-2018, the domination of subtypes 1a (34.01%), 1b (28.34%) and genotype 3 (23.89%) was registered. In 2012 and 2013, HCV subtype 1a was the most common (27/63; 42.86% and 17/40; 42.50%, respectively). In 2014, the leading HCV genotype/subtype were 3 and 1b (17/57; 29.82%). In 2015, the dominance of HCV genotype 3 (14/39; 35.90%) continued, while in 2016, the same number of HCV subtypes 1a and 1b (11/30; 36.67%) was recorded. Although in a small number of tested, during 2017, HCV subtype 1b was the most prevalent (7/14; 50.00%), and in 2018, it was replaced by a HCV subtype 1a (3/4; 75.00%). Distribution of HCV genotypes/subtypes by age group of patients varied significantly (p=0.000). The largest number of patients (71/247; 28.74%) belonged to the age category 30-39 years and HCV genotypes/subtypes 1, 3, 4, 1a and 1b were identified. Except in 2017, male gender significantly dominated (p=0.000). In males, HCV subtype 1a (68/170; 40.00%) was the most common, while in women it was HCV subtype 1b (44/77; 57.14%).Conclusion: This six-year retrospective study showed the time variations of the circulating HCV genotypes/subtypes among patients with chronic hepatitis C in Canton Sarajevo. Genotyping of the HCV has an important implications for diagnosis and treatment of the patients.


2019 ◽  
Vol 7 (1) ◽  
pp. 1-6
Author(s):  
Hosein Mehdipour ◽  
Yaghoub Moaddab ◽  
Khalil Azizian ◽  
Morteza Ghojazadeh ◽  
Mohammad Hossein Somi

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


2014 ◽  
Vol 59 (3) ◽  
pp. 1505-1511 ◽  
Author(s):  
Warren Kati ◽  
Gennadiy Koev ◽  
Michelle Irvin ◽  
Jill Beyer ◽  
Yaya Liu ◽  
...  

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.


2017 ◽  
Vol 239 ◽  
pp. 1-8 ◽  
Author(s):  
Wasun Chantratita ◽  
Keum-Soo Song ◽  
Choi GunHo ◽  
Viroj Pongthanapisith ◽  
Nipa Thongbaiphet ◽  
...  

2019 ◽  
Vol 70 (1) ◽  
pp. e500
Author(s):  
Chen-Hua Liu ◽  
Tung-Hung Su ◽  
Chun-Jen Liu ◽  
Chun-Ming Hong ◽  
Hung-Chih Yang ◽  
...  

2016 ◽  
Vol 36 (10) ◽  
pp. 1433-1441 ◽  
Author(s):  
Jia-Horng Kao ◽  
Youn-Jae Lee ◽  
Jeong Heo ◽  
Sang-Hoon Ahn ◽  
Young-Suk Lim ◽  
...  

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