ABSTRACT
Introdução: Um dos fatores limitantes da eficácia da terapia antiviral no tratamento da infecção pelo vírus da Hepatite C (HCV) com o uso de inibidores de protease (IP) é o surgimento de resistência causada por mutações pontuais. Objetivo: Analisar a prevalência de mutações na região da serino-protease da NS3 associadas à resistência aos IP em pacientes infectados pelos subtipos 1a e 1b do HCV. Métodos: Extração de RNA viral, reação de PCR com primers específicos para cada subtipo e purificação seguida pela reação de sequenciamento nucleotídico foram realizadas. As sequências obtidas abrangendo os nucleotídeos 3466-3961 do genoma do HCV foram editadas no programa MEGA 6.0. As substituições observadas nas posições de aminoácidos associadas à resistência aos IP foram relacionadas após submissão ao site geno2pheno. Resultados: Um total de 65 amostras (Subtipo 1a: n=47; Subtipo 1b: n=18) de pacientes não-respondedores ao tratamento prévio por terapia dupla IFN/RBV (n=8) ou terapia tripla com IP boceprevir ou telaprevir (n=15) e virgens de tratamento (n=42) foram sequenciadas...
Introduction: One of the limiting factors of the effectiveness of the antiviral therapy ofhepatitis C virus (HCV) infection with the use of protease inhibitors (PI) is theemergence of resistance due to point mutations. Aim: To analyze the prevalence ofmutations in the HCV NS3 serine protease associated with PI resistance in patientsinfected with subtypes 1a and 1b of HCV. Methods: Viral RNA extraction, PCRreactions with specific primers for each subtype and purification followed bynucleotide sequencing reaction were performed. The obtained sequences coveringnucleotides 3466-3961 of the HCV genome were analyzed by MEGA 6.0 program.The substitutions observed in the amino acid positions associated with PI resistancewere related after submission to the site geno2pheno. Results: A total of 65 samples(subtype 1a: n=47; subtype 1b: n=18) of non-responding patients to previoustreatment by dual therapy IFN/RBV (n=8) or triple therapy with PI boceprevir ortelaprevir (n=15) and treatment-naïve patients (n=42) were sequenced...
Subject(s)
Male , Female , Humans , Hepatitis C , Mutation , Protease InhibitorsABSTRACT
Inosine triphosphatase (ITPA) single nucleotide polymorphisms (SNPs) are strongly associated with protection against ribavirin (RBV)-induced anaemia in European, American and Asian patients; however, there is a paucity of data for Brazilian patients. The aim of this study was to evaluate the ITPA SNP (rs7270101/rs1127354) frequency in healthy and hepatitis C virus (HCV)-infected patients from Brazil and the association with the development of severe anaemia during antiviral therapy. ITPA SNPs were determined in 200 HCV infected patients and 100 healthy individuals by sequencing. Biochemical parameters and haemoglobin (Hb) levels were analysed in 97 patients who underwent antiviral therapy. A combination of AArs7270101+CCrs1127354 (100% ITPase activity) was observed in 236/300 individuals. Anaemia was observed in 87.5% and 86.2% of treated patients with AA (rs7270101) and CC genotypes (rs1127354), respectively. Men with AA (rs7270101) showed a considerable reduction in Hb at week 12 compared to those with AC/CC (p = 0.1475). In women, there was no influence of genotype (p = 0.5295). For rs1127354, men with the CC genotype also showed a sudden reduction in Hb compared to those with AC. Allelic distribution of rs7270101 and rs1127354 shows high rates of the genotypes AA and CC, respectively, suggesting that the study population had a great propensity for developing RBV-induced anaemia. A progressive Hb reduction during treatment was observed; however, this reduction was greater in men at week 12 than in women.
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