scholarly journals The effectiveness and safety of sofosbuvir‐ledipasvir for patients with hepatitis C virus genotype 2 infection

2021 ◽  
Author(s):  
Po‐Yueh Chen ◽  
Hsin‐Yi Yang ◽  
Chu‐Kuang Chou ◽  
Li‐Jen Chang ◽  
Ming‐Tse Hsu ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Genotype ◽  
Genotype 2

scholarly journals Interplay of Amino Acid Residues at Positions 28 and 31 in NS5A Defines Resistance Pathways in Hepatitis C Virus Genotype 2

2019 ◽  
Vol 63 (12) ◽  
Author(s):  
Ernest Asante-Appiah ◽  
Paul Ingravallo ◽  
Patricia McMonagle ◽  
Karin Bystol ◽  
Ellen Xia ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Amino Acid ◽  
Treatment Outcomes ◽  
Cross Talk ◽  
Site Directed Mutagenesis ◽  
Virus Genotype ◽  
Ns5a Inhibitor ◽  
Genotype 2 ◽  
Antiviral Activities

ABSTRACT Hepatitis C virus (HCV) genotype 2 (GT2) represents approximately 9% of all viral infections globally. While treatment outcomes for GT2-infected patients have improved substantially with direct-acting antiviral agents (DAAs) compared to alpha interferon, the presence of polymorphisms in NS5A can impact the efficacy of NS5A inhibitor-containing regimens. Thus, pathways of NS5A resistance were explored in GT2 subtypes using elbasvir, an NS5A inhibitor with broad genotype activity. Resistance selection studies, resistance analysis in NS5A-inhibitor treated virologic failures, and analyses of antiviral activities in replicons bearing a panel of GT2 subtype sequences and amino acid substitutions introduced by site-directed mutagenesis were performed to define determinants of inhibitor susceptibility. Elbasvir showed differential antiviral activities in replicons bearing GT2 sequences. The 50% effective concentration (EC50) values for replicons bearing reference NS5A sequences for GT2a and GT2b were 0.003 and 3.4 nM, respectively. Studies performed with recombinant replicons demonstrated cross talk between amino acid positions 28 and 31. The combination of phenylalanine and methionine at positions 28 and 31, respectively, conferred the highest potency reduction for elbasvir in GT2a and GT2b. This combination was observed in failures seen in the C-SCAPE trial. Addition of grazoprevir, an NS3/4A protease inhibitor, to elbasvir more effectively suppressed the emergence of resistance in GT2 at modest inhibitor concentrations (3× EC90). Ruzasvir, a potent, pan-genotype NS5A inhibitor, successfully inhibited replicons bearing GT2 resistance-associated substitutions (RASs) at positions 28 and 31. The results demonstrate that cross talk between amino acids at positions 28 and 31 in NS5A modulated inhibitor potency and may impact treatment outcomes in some HCV GT2-infected patients.

Possible determinants of rapid virological response suggesting shorter courses of combination therapy for hepatitis C virus genotype 2

Hepatology ◽  
2008 ◽  
Vol 48 (1) ◽  
pp. 342-342 ◽  
Author(s):  
Chia‐Yen Dai ◽  
Wan‐Long Chuang ◽  
Jee‐Fu Huang ◽  
Ming‐Yen Hsieh ◽  
Ming‐Lung Yu
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Combination Therapy ◽  
Virological Response ◽  
Rapid Virological Response ◽  
Virus Genotype ◽  
Genotype 2

scholarly journals Full-length sequences of 11 hepatitis C virus genotype 2 isolates representing five subtypes and six unclassified lineages with unique geographical distributions and genetic variation patterns

2012 ◽  
Vol 93 (6) ◽  
pp. 1173-1184 ◽  
Author(s):  
Chunhua Li ◽  
Hong Cao ◽  
Ling Lu ◽  
Donald Murphy
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Complete Genome ◽  
Pcr Amplification ◽  
Full Length ◽  
African Origin ◽  
Genome Sequences ◽  
Virus Genotype ◽  
Variation Patterns ◽  
Genotype 2

In this study, we characterized full-length hepatitis C virus (HCV) genome sequences for 11 genotype 2 isolates. They were isolated from the sera of 11 patients residing in Canada, of whom four had an African origin. Full-length genomes, each with 18–25 overlapping fragments, were obtained by PCR amplification. Five isolates represent the first complete genomes of subtypes 2d, 2e, 2j, 2m and 2r, while the other six correspond to variants that do not group within any assigned subtypes. These sequences had lengths of 9508–9825 nt and each contained a single ORF encoding 3012–3106 aa. Predicted amino acids were carefully inspected and unique variation patterns were recognized, especially for a 2e isolate, QC64. Phylogenetic analysis of complete genome sequences provides evidence that there are a total of 16 subtypes, of which 11 have been described here. Co-analysis with 68 partial NS5B sequences also differentiated 18 assigned subtypes, 2a–2r, and eight additional lineages within genotype 2, which is consistent with the analysis of complete genome sequences. The data from this study will now allow 10 assigned subtypes and six additional lineages of HCV genotype 2 to have their full-length genomes defined. Further analysis with 2021 genotype 2 sequences available in the HCV database indicated that the geographical distribution of these subtypes is consistent with an African origin, with particular subtypes having spread to Asia and the Americas.

scholarly journals Efficacy of Sofosbuvir, Velpatasvir, and GS-9857 in Patients With Hepatitis C Virus Genotype 2, 3, 4, or 6 Infections in an Open-Label, Phase 2 Trial

2016 ◽  
Vol 151 (5) ◽  
pp. 902-909 ◽  
Author(s):  
Edward J. Gane ◽  
Kris V. Kowdley ◽  
David Pound ◽  
Catherine A.M. Stedman ◽  
Mitchell Davis ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Phase 2 ◽  
Virus Genotype ◽  
Open Label ◽  
Phase 2 Trial ◽  
Genotype 2 ◽  
Open Label Phase

scholarly journals Randomized trial of albinterferon alfa-2b every 4 weeks for chronic hepatitis C virus genotype 2/3

2012 ◽  
Vol 19 (9) ◽  
pp. 623-634 ◽  
Author(s):  
S. Pianko ◽  
S. Zeuzem ◽  
W.-L. Chuang ◽  
G. R. Foster ◽  
S. K. Sarin ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Randomized Trial ◽  
Chronic Hepatitis C ◽  
Virus Genotype ◽  
Genotype 2 ◽  
Chronic Hepatitis C Virus

Efficacy of Sofosbuvir Plus Ribavirin in Veterans With Hepatitis C Virus Genotype 2 Infection, Compensated Cirrhosis, and Multiple Comorbidities

2017 ◽  
Vol 15 (2) ◽  
pp. 282-288 ◽  
Author(s):  
Samuel B. Ho ◽  
Alexander Monto ◽  
Adam Peyton ◽  
David E. Kaplan ◽  
Sean Byrne ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Genotype ◽  
Compensated Cirrhosis ◽  
Genotype 2
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