Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Sep;31(3):220-228.
doi: 10.1007/s13337-020-00616-9. Epub 2020 Aug 4.

Major mutations in the NS3 gene region of hepatitis C virus related to the resistance to direct acting antiviral drugs: a systematic review

Ana Elisa de Figueiredo Miranda Mundim  1 , Fernanda de Oliveira Feitosa de de Castro  1 , Marina Brandão Braz Albuquerque  1 , Cesar Augusto Sam Tiago Vilanova-Costa  2 , Irmtraut Araci Hoffmann Pfrimer  1 , Antonio Márcio Teodoro Cordeiro Silva  1
Affiliations
Review

Major mutations in the NS3 gene region of hepatitis C virus related to the resistance to direct acting antiviral drugs: a systematic review

Ana Elisa de Figueiredo Miranda Mundim et al. Virusdisease. 2020 Sep.

Abstract

Hepatitis C virus (HCV) remains a global public health problem with high prevalence rates and chronicity of infection. Present work aimed to describe the main mutations in the NS3 region of the HCV genome related to the resistance of patients to the currently available direct-acting antivirals (DAAs). To guide the study description, the preferred items in the PRISMA protocol for systematic review were used. The data collected were HCV genotypes and subtypes and mutations in HCV NS3, general and stratified by continent. The 10 papers selected for this systematic review reported studies in seven countries, on three continents, and generated data of 2937 patients. The most frequent HCV subtype was 1a. Prevalence of genotypes suggested that there were few demographic regions reached by the studies, since there were regional variations in the type of genotypes reported in the available bibliographies. Of the total study population, 35.3% (n = 1037) had mutations in the NS3 gene region of HCV, suggesting a high rate of resistance to DAAs and a low sustained virologic response among those who used some therapeutic option. Ten major mutations were identified: Q80K, V170I, S122G, V36L, T54S, D168Q, A156S, Q80G, S122R, and V55A. The Q80K mutation was the highlight of the study, appearing not only with greater representativity (61.6%) but also as the only one described in the three continents analyzed. This systematic review reinforces the need to carry out more studies of detection of these mutations to fill in all information gaps that might help in optimization of treatment.

Keywords: Direct-acting antivirals; HCV subtype; Hepatitis C virus; NS3 gene; Q80K mutation.

PubMed Disclaimer

Conflict of interest statement

Conflict of interestNo potential conflicts of interest.

Figures

Fig. 1
Fig. 1
Distribution of different hepatitis C virus subtypes among 2937 infected patients. Systematic review, 2013–2018
Fig. 2
Fig. 2
Distribution of different hepatitis C virus subtypes among 2937 infected patients, stratified by continent. Systematic review, 2013–2018
Fig. 3
Fig. 3
Distribution of the mutation types found in the 1037 HCV-infected patients who presented alterations in the NS3 region of the virus genome. Systematic review, 2013–2018
Fig. 4
Fig. 4
Frequency of each mutation type on each continent. Systematic review, 2013–2018
Fig. 5
Fig. 5
Frequency of each mutation type by viral genotype. Systematic review, 2013–2018
See this image and copyright information in PMC

References

    1. Ahmed A, Felmlee DJ. Mechanisms of hepatitis C viral resistance to direct acting antivirals. Viruses. 2015;7(12):6716–6729. doi: 10.3390/v7122968. - DOI - PMC - PubMed
    1. Chen ZW, Li H, Ren H, Hu P. Global prevalence of pre-existing HCV variants resistant to direct-acting antiviral agents (DAAs): mining the GenBank HCV genome data. Sci Rep. 2016;6:20310. doi: 10.1038/srep20310. - DOI - PMC - PubMed
    1. Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science. 1989;244:359–362. doi: 10.1126/science.2523562. - DOI - PubMed
    1. de Sousa MR, Ribeiro ALP. Systematic review and meta-analysis of diagnostic and prognostic studies: a tutorial. Arq Bras Cardiol. 2009;92:241–251. doi: 10.1590/S0066-782X2009000300013. - DOI - PubMed
    1. Dietz J, Susser S, Berkowski C, Perner D, Zeuzem S, Sarrazin C. Consideration of viral resistance for optimization of direct antiviral therapy of hepatitis C virus genotype 1-infected patients. PLoS ONE. 2015 doi: 10.1371/journal.pone.0134395. - DOI - PMC - PubMed

LinkOut - more resources