Estudo Molecular dos V??rus B e C das Hepatites nas Regi??es Norte e Nordeste do Brasil

Infec????es pelos v??rus B e C das hepatites constituem um significante problema de sa??de p??blica em todo mundo. Mais de 350 milh??es de pessoas est??o cronicamente infectadas pelo VHB e 170 milh??es pelo VHC. No Brasil, a preval??ncia de pessoas infectadas pelo VHB varia de baixa endemicidade (<2%) at?? alta, (>7%), e estima-se que 1,5% da popula????o esteja infectada pelo VHC (WHO). Estudos recentes tem demonstrado consider??veis varia????es entre os isolados do VHB, confirmando a diversidade de gen??tipos do v??rus circulantes e o surgimento de muta????es no genoma viral que podem ter impacto na resposta terap??utica e imune. Informa????es sobre a diversidade gen??tica do VHB ser??o de grande valor para determinar fatores de risco associados a dissemina????o do v??rus e auxiliar na ado????o de medidas de preven????o e terap??utica. A infec????o pelo VHC tornou-se um s??rio problema de saude p??blica desde que n??o existe uma vacina dispon??vel e o tratamento ?? extremamente caro para os ??rg??os p??blicos como desgastante para o paciente. Este trabalho utilizou as ferramentas moleculares e de epidemiologia no estudo destes v??rus para caracterizar molecularmente os v??rus B e C das hepatites nas Regi??es Norte e Nordeste, particularmente na Bahia, atrav??s de sequenciamento de DNA e an??lises filogen??ticas. Amostras de pacientes provenientes da Bahia, Acre, Rondonia, Amazonas, Maranh??o e Tocantins foram analisadas. As amostras foram oriundas de outros estudos e de centros de refer??ncia para tratamento das hepatites, sendo avaliadas 635 amostras para o VHC e 335 de VHB. Sequencias das regi??es pr??-S/S e pr??- Core/Core do VHB e NS5b, 5UTR, E1 e Core do VHC foram utilizadas para classifica????o genot??pica e an??lise filogenetica. Os gen??tipos mais frequentes para o VHB foram A (57%), D (10%) e F(33%) na Bahia e nas amostras da regi??o Norte. N??s encontramos em nosso estudo 55,6% de pacientes co-infectados com VHB/Delta. N??o foi poss??vel estabelecer uma liga????o gen??tipo espec??fico com a evolu????o da infec????o, e determinar a presen??a de mutantes relacionados ?? resposta terap??utica e ao escape imunol??gico. Com rela????o ao VHC, a subtipagem dos isolados foi realizada atrav??s do sequenciamento da regi??o NS5b e 5UTR (n=230). Os sub-gen??tipos mais frequentes foram 1a(45,6%), 1b (46,9%), 3a (6,5%) e 2a/b(0,8%). As regi??es E1 e Core tamb??m foram sequenciadas e no futuro ser??o utilizadas para avaliar possiveis muta????es. O presente estudo mostra que a aplica????o de protocolos de sequenciamento, bioinform??tica e filogenia s??o indispens??veis para a compreens??o da epidemiologia molecular dos v??rus das hepatites.Infections with hepatitis B and C viruses constitute a significant public health problem worldwide. More than 350 million people are chronically infected with HBV and 170 million by HCV. In Brazil, HBV remains endemic despite widespread vaccination with prevalence of infection ranging from (<2%) low endemicity, until high (>7%) in different regions. Prevalence of HCV infection in Brazil has been estimated at 1.5%. Recent studies have shown considerable genetic variation among HBV isolates, confirming the diversity of circulating genotypes of the virus and the emergence of mutations in the viral genome that may impact on therapeutic and immune response. Information on the genetic diversity of HBV is useful for molecular epidemiology to determine risk factors associated with the spread of the virus and to inform prevention strategies and for monitoring therapy. Because there is no vaccine available to prevent HCV infection and treatment is extremely expensive for public agencies, HCV is an emerging public health problem. The treatment efficiency is directly related to viral genotype. In this study molecular epidemiology tools were used to characterize HBV and HCV in the North and Northeast, particularly in Bahia, through DNA sequencing and phylogenetic analysis. Samples from Bahia, Acre, Rond??nia, Amazonas, Maranh??o and Tocantins were analyzed. The samples were collected in collaboration with other studies and centers of references for hepatitis treatments. 635 samples from HCV infected patients and 335 samples from HBV infected were evaluated. Sequences of the regions pre-S / S, HBV core / pre-core, NS5B, 5UTR, HCV Core and E1 were used for genotypic classification and phylogenetic analysis. The most frequent HBV genotypes were A (57%), D (10%) and F (33%) in Bahia and in the samples from the North region. Fifty five percent of the patients from Rond??nia were coinfected with HBV and HDV. In this study, we were unable to establish a connection with the particular genotype evolution of the infection and determine the presence of mutants related to therapeutic response and immune escape. In the North region co-infection with HBV genotype F and D virus is strongly associated with poor outcome of the disease as informed by the physicians and literature. Regarding HCV, the subtyping of isolates was performed by sequencing the NS5B region and 5UTR (n=230). The sub-genotypes more frequent were 1a (45.6%), 1b (46.9%), 3a (6.5%) and 2a / b (0.8%). The Core and E1 regions were also sequenced and in the future could be used to evaluate possible mutations. This study shows that the implementation of protocols for sequencing, bioinformatics and phylogenetic are essential for understanding the molecular epidemiology of hepatitis