부산대학교 도서관

Ana Paula de Torres Santos,1,2 Vanessa Cristina Martins Silva,1 Maria Cássia Mendes-Corrêa,3 Marcilio Figueiredo Lemos,1 Fernanda de Mello Malta,4 Rúbia Anita Ferraz Santana,5 Gregório Tadeu Fernando Dastoli,5 Vanessa Fusco Duarte de Castro,5 João Renato Rebello Pinho,2,4,5 Regina Célia Moreira1 1Laboratory of Viral Hepatitis, Virology Center, Instituto Adolfo Lutz, São Paulo, SP, Brazil; 2Divisão de Laboratório Central, Laboratório de Imunologia, Faculdade de Medicina, Hospital das Clínicas, Universidade de São Paulo, São Paulo, SP, Brazil; 3LIM-52-Institute of Tropical Medicine, Department of Infectious Diseases, School of Medicine, University of São Paulo, São Paulo, SP, Brazil; 4Laboratory of Tropical Gastroenterology and Hepatology “João de Queiroz and Castorina Bettencourt Alves”‑LIM 07‑Institute of Tropical Medicine Department of Gastroenterology, School of Medicine, University of São Paulo, São Paulo, SP, Brazil; 5Albert Einstein Medicina Diagnóstica, Hospital Israelita Albert Einstein, São Paulo, SP, BrazilCorrespondence: Regina Célia MoreiraInstituto Adolfo Lutz, Centro de Virologia, Av: Dr Arnaldo, 355 Pacaembu, SP, Cep 01246-000, BrazilTel +55 11 30682911Email regina.moreira@ial.sp.gov.brPurpose: Globally, it is estimated that 71 million people are chronically infected with hepatitis C, and 10– 20% of these will develop cirrhosis and hepatocellular carcinoma. The development of new direct-acting antiviral (DAA) drugs has contributed to sustained virological response (SVR), eliminating the infection and achieving cure of chronic hepatitis C. However, treated patients can develop HCV resistance to DAAs, which can contribute to the failure of treatment. Here, we aimed to evaluate the prevalence and specific pattern of NS5A and NS5B resistance-associated substitutions (RAS) in samples from patients chronically infected with HCV genotype 3a at a public health laboratory, Instituto Adolfo Lutz, São Paulo, Brazil.Patients and Methods: Serum samples from the enrolled individuals were submitted to “in-house” polymerase chain reaction amplification of NS5A and NS5B non-structural protein genes, which were then sequenced by Sanger method.Results: A total of 170 and 190 samples were amplified and analyzed for NS5A and NS5B, respectively. For NS5A, 20 (12.0%) samples showed some important RAS; 16 (9.0%) showed some type of substitution and 134 (79.0%) showed no polymorphism. No sample showed any RAS for NS5B.Conclusion: This study found important RAS in samples from naïve chronic HCV patients in some areas from São Paulo. The most prevalent were A62S, A30K, and Y93H, which could indicate an increase in resistance to some DAAs used in HCV treatment.Keywords: HCV, nonstructural NS5A/NS5B, resistance, polymorphism, RAS