Major mutations in the NS3 gene region of hepatitis C virus related to the resistance to direct acting antiviral drugs:
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ORIGINAL ARTICLE
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 Mundim1 • Fernanda de Oliveira Feitosa de de Castro1 Marina Branda˜o Braz Albuquerque1 • Cesar Augusto Sam Tiago Vilanova-Costa2 • Irmtraut Araci Hoffmann Pfrimer1 • Antonio Ma´rcio Teodoro Cordeiro Silva1
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Received: 10 February 2020 / Accepted: 20 July 2020 Indian Virological Society 2020
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 & Antonio Ma´rcio Teodoro Cordeiro Silva [email protected] 1
Programa de Po´s-Graduac¸a˜o em Cieˆncias Ambientais e Sau´de, Pontifı´cia Universidade Cato´lica de Goia´s, Avenida ´ rea 4, Universita´ria 1.440, Setor Universita´rio, Campus 1, A Goiaˆnia, GO CEP: 74605-010, Brazil
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Laborato´rio de Biologia Tumoral e Oncogene´tica, Hospital Arau´jo Jorge, Associac¸a˜o de Combate ao Caˆncer em Goia´s, Goiaˆnia, GO, Brazil
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 Hepatitis C virus NS3 gene HCV subtype Q80K mutation Direct-acting antivirals
Introduction The hepatitis C virus (HCV) has been known since 1975, when researchers concluded that most cases of post-transfusion hepatitis were not caused by infections of hepatitis A or hepatitis B viruses but by those of another unknown infectious agent [6]. In 1989, Choo et al. [3] decoded the complementary DNA of the HCV RNA using samples from experimentally infected chimpanzees. In the years that followed, there was an evolution of HCV studies
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