scholarly journals Prevalence of Naturally-Occurring NS5A and NS5B Resistance-Associated Substitutions in Iranian Patients With Chronic Hepatitis C Infection

2021 ◽  
Vol 11 ◽  
Author(s):  
Pooneh Rahimi ◽  
Heidar Sharafi ◽  
Golnaz Bahramali ◽  
FaridehSadat SajadianFard ◽  
Nafiseh Sadat Asadi ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Amino Acid ◽  
Web Application ◽  
Antiviral Agents ◽  
Amino Acid Substitutions ◽  
Hepatitis C Infection ◽  
Cross Sectional ◽  
Naturally Occurring ◽  
Ns5a Region ◽  
Iranian Patients

BackgroundHepatitis C virus (HCV), non-structural 5A (NS5A), and non-structural 5B (NS5B) resistance-associated substitutions (RASs) are the main causes of failure to direct-acting antiviral agents (DAAs). NS5A and NS5B RASs can occur in patients with HCV infection naturally and before exposure to DAAs.ObjectivesThis study aimed to evaluate naturally-occurring NS5A and NS5B RASs in Iranian patients with HCV genotype 1a (HCV-1a) and -3a infections.MethodsIn this cross-sectional study, viral RNA was extracted from serum specimens. NS5A and NS5B regions were amplified using RT-PCR followed by DNA sequencing. The results of nucleotide sequences were aligned against reference sequences of HCV-1a and -3a and the amino acid substitutions were analyzed using geno2pheno [hcv] web application.ResultsAmong 135 patients with hepatitis C, NS5A amino acid substitutions/RASs were identified in 26.4% and 15.9% of patients with HCV-1a and -3a infections, respectively. The identified amino acid substitutions/RASs in the NS5A region of patients with HCV-1a infection were M28T/V/I 11.1%, Q30R/H 4.2%, L31M 1.4%, and H58Y/P/C/D/Q/S/T 16.7%. Y93H substitution was not found in HCV-1a sequences. In patients with HCV-3a infection, NS5A amino acid substitutions/RASs were A30T/K 9.5%, L31F 1.6%, P58S/T/C 3.2%, Y93H 3.2%, and Y93N 3.2%. No resistance substitutions were identified in NS5B sequences from patients with HCV-1a and -3a infections.ConclusionIn this study, baseline amino acid substitutions/RASs were only identified in the NS5A region in Iranian patients with HCV-1a and -3a infections, and the prevalence of these amino acid substitutions/RASs were in accordance with similar studies. There were no RASs in the HCV-1a and -3a NS5B region.

scholarly journals Amino Acid Substitutions Associated with Treatment Failure for Hepatitis C Virus Infection

2020 ◽  
Vol 58 (12) ◽  
Author(s):  
María Eugenia Soria ◽  
Carlos García-Crespo ◽  
Brenda Martínez-González ◽  
Lucía Vázquez-Sirvent ◽  
Rebeca Lobo-Vega ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Amino Acid ◽  
Treatment Failure ◽  
Antiviral Agents ◽  
Three Dimensional ◽  
Sustained Viral Response ◽  
Amino Acid Substitutions ◽  
Hepatitis C Virus Infection ◽  
Bona Fide

ABSTRACT Despite the high virological response rates achieved with current directly acting antiviral agents (DAAs) against hepatitis C virus (HCV), around 2% to 5% of treated patients do not achieve a sustained viral response. The identification of amino acid substitutions associated with treatment failure requires analytical designs, such as subtype-specific ultradeep sequencing (UDS) methods, for HCV characterization and patient management. Using this procedure, we have identified six highly represented amino acid substitutions (HRSs) in NS5A and NS5B of HCV, which are not bona fide resistance-associated substitutions (RAS), from 220 patients who failed therapy. They were present frequently in basal and posttreatment virus of patients who failed different DAA-based therapies. Contrary to several RAS, HRSs belong to the acceptable subset of substitutions according to the PAM250 replacement matrix. Their mutant frequency, measured by the number of deep sequencing reads within the HCV quasispecies that encode the relevant substitutions, ranged between 90% and 100% in most cases. They also have limited predicted disruptive effects on the three-dimensional structures of the proteins harboring them. Possible mechanisms of HRS origin and dominance, as well as their potential predictive value for treatment response, are discussed.

scholarly journals Naturally Occurring Resistance-Associated Variants to Hepatitis C Virus Direct-Acting Antiviral Agents in Treatment-Naive HCV Genotype 6a-Infected Patients

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Zhanyi Li ◽  
Ying Liu ◽  
Ying Zhang ◽  
Xiaoqiong Shao ◽  
Qiumin Luo ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Agents ◽  
Direct Acting Antiviral ◽  
Naturally Occurring ◽  
Ns5a Region ◽  
Treatment Naïve ◽  
Direct Acting ◽  
The Impact ◽  
Direct Acting Antiviral Agents

Background and Objective. The direct-acting antiviral agents (DAAs) antiviral therapy has drastically improved the prognosis of hepatitis C virus (HCV) patients. However, the viral drug resistance-associated variants (RAVs) can limit the efficacy of DAAs. For the HCV-6a is not the predominant prevalent genotype; the data on the prevalence of naturally occurring RAVs in it is scarce. Our study aims to assess the prevalence of RAVs in treatment-naive HCV-6a patients. Methods. Nested PCR assays were performed on 95 HCV-6a patients to amplify HCV viral regions of NS3, NS5A, and NS5B. Results. In NS3/4A region, we detected Q80K in 95.5% isolates (84/88) and D168E in 2.3% isolates (2/88). In NS5A region, we detected Q30R in 93.2% isolates (82/88), L31M in 4.6% isolates (4/88), and H58P in 6.8% isolates (6/88). In NS5B region, we detected A15G in 2.3% isolates (2/88), S96T in 1.1% isolates (1/88), and S282T in 20.7% isolates (17/88) and we detected I482L in 100% isolates (4/4), V494A in 50% isolates (2/4), and V499A in 100% isolates (4/4). Conclusions. RAVs to DAAs preexist in treatment-naive HCV-6a patients. Further studies should address the issue of the impact of RAVs in response to DAA therapies for HCV-6a patients.

scholarly journals Prevalence of hepatitis C virus among healthy donors at a large Teaching Hospital in Lahore, Pakistan: A cause of concern for health policy makers.

2019 ◽  
Vol 26 (09) ◽  
pp. 1413-1418
Author(s):  
Samreen Hameed ◽  
Syed Maaz Abdullah ◽  
Asad Ali ◽  
Sarmad Zahoor ◽  
Rabia Amin Butt ◽  
...  
Keyword(s):  
Health Policy ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Blood Donors ◽  
Antiviral Agents ◽  
Rapid Test ◽  
Cross Sectional Study ◽  
Hepatitis C Infection ◽  
Cross Sectional ◽  
Policy Makers

Objectives: Hepatitis C Virus (HCV) infection is life threatening but with the advent of new antiviral agents is potentially curable. Its prevalence among healthy blood donors was estimated in Mayo Hospital, Lahore, Pakistan. The aim of this study was to help in estimating disease burden in addition to early diagnosis of asymptomatic individuals necessitating treatment. Study Design: Retrospective single centre cross-sectional study. Setting: Mayo Hospital, Lahore, Pakistan. Period: January 2016 to December 2017. Material and Methods: Blood donors were tested for Anti-HCV antibodies by qualitative test based on lateral flow immunoassay using commercially made rapid test kits. Results: In 2016 and 2017, a total of 76530 healthy blood donors were screened for anti-HCV antibodies. Out of 76530 donors, 2095 were found to have anti-HCV antibodies constituting cumulative percentage of 2.73%. The seroprevalence was 2.49% in 2016 and reached to 2.97% in 2017. Conclusion: Sero-prevalence of Hepatitis C among healthy blood donors is quite high at 2.73% and has slightly increased in 2017 compared to 2016. This dictates need for continued community awareness for prevention, early detection, and treatment. This study will be helpful for health policy makers to design more effective strategic planning to eradicate Hepatitis C infection.

Prevalence of naturally occurring amino acid substitutions associated with resistance to hepatitis C virus NS3/NS4A protease inhibitors in São Paulo state

2018 ◽  
Vol 163 (10) ◽  
pp. 2757-2764 ◽  
Author(s):  
Regina Célia Moreira ◽  
Ana Paula de Torres Santos ◽  
Gaspar Lisboa-Neto ◽  
Maria Cássia Jacintho Mendes-Corrêa ◽  
Marcilio Figueiredo Lemos ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Amino Acid ◽  
Protease Inhibitors ◽  
Sao Paulo ◽  
Amino Acid Substitutions ◽  
São Paulo ◽  
Paulo State ◽  
Naturally Occurring ◽  
São Paulo State

scholarly journals Amino acid substitutions associated with treatment failure of hepatitis C virus infection

2020 ◽  
Author(s):  
María Eugenia Soria ◽  
Carlos García-Crespo ◽  
Brenda Martínez-Gónzalez ◽  
Lucía Vázquez-Sirvent ◽  
Rebeca Lobo-Vega ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Amino Acid ◽  
Treatment Failure ◽  
Deep Sequencing ◽  
Antiviral Agents ◽  
Three Dimensional ◽  
Sustained Viral Response ◽  
Amino Acid Substitutions ◽  
Bona Fide

AbstractDespite the high virological response rates achieved with current directly-acting antiviral agents (DAAs) against hepatitis C virus (HCV), around 2% to 5% of treated patients do not achieve a sustained viral response. Identification of amino acid substitutions associated with treatment failure requires analytical designs, such as subtype-specific ultra-deep sequencing (UDS) methods for HCV characterization and patient management. Using this procedure, we have identified six highly represented amino acid substitutions (HRSs) in NS5A and NS5B of HCV from 220 patients who failed therapy, which are not bona fide resistance-associated substitutions (RAS). They were present frequently in basal and post-treatment virus of patients who failed therapy to different DAA-based therapies. Contrary to several RAS, HRSs belong to the acceptable subset of substitutions according to the PAM250 replacement matrix. Coherently, their mutant frequency, measured by the number of deep sequencing reads within the HCV quasispecies that encode the relevant substitutions, ranged between 90% and 100% in most cases. Also, they have limited predicted disruptive effects on the three-dimensional structures of the proteins harboring them. Possible mechanisms of HRS origin and dominance, as well as their potential predictive value of treatment response are discussed.

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