Caracterização molecular do vírus da hepatite B em pacientes cronicamente infectados em um centro de referência em Goiânia-GO

Detalhes bibliográficos
Autor(a) principal: Santos, Norrama Araújo
Data de Publicação: 2019
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da UFG
dARK ID: ark:/38995/001300000664b
Texto Completo: http://repositorio.bc.ufg.br/tede/handle/tede/9576
Resumo: Genotypes of hepatitis B virus and the occurrence of mutations in the genome may interfere with treatment response, disease progression to chronic form, cirrhosis and hepatocellular carcinoma. The objective of the present study was to analyze the molecular characteristics of HBV in patients with chronic hepatitis B in Goiânia-Goiás. Blood samples (N = 53) were collected from patients who were attended / followed at a referral hospital in Goiânia-Goiás. Initially, an interview was conducted with structured questionnaire on sociodemographic data, possible characteristics associated with the risk of HBV acquisition and previous vaccination against hepatitis B. Other information, such as clinical data, use of antiviral therapy and results of complementary tests were collected in the medical record and with the doctor in charge. All samples were screened for HBV serological markers (HBsAg, Anti-HBc, Anti-HBs, HBeAg and Anti-HBe) using commercial kits. Subsequently, viral DNA extraction and a semi- nested PCR were performed using primers complementary to the Pre-S / S (PS1, S2 / S22 and SR) and Pre-C / C (X1, C2, X4 and C3) regions of HBV. Then the samples were sequenced to the S and PreC / C regions of HBV for the determination of genotypes / subgenotypes and mutation screening. The nucleotide sequencing was performed in 22 samples, and the genotypes / subgenotypes A1 (n = 09), A2 (n = 01), D2 (n = 02), D3 (n = 07), and F2 were found. Mutations in the Pre C / C region (S171T, G1764A), region S (S45T, P46T, T114S, K122T, T123T, T143S, A159G, Y161F, I213L, L21S, T118A, V47G, P127L, F183C, M198I. Y206C, R24K, S61L, F8S, T127P, I68T, Y100C) and P region (I91L, Y126H, W153R, Y126R, V207L, L129M, Q130P) were identified and previously described in the literature, in patients with chronic hepatitis B. Furthermore, the presence of some nucleotide substitutions in the S regions (V47G, L42C, L14S, V14C, L15Y, Q16R, A17R, G44A, L49P, H61L, F158L, P178Q, F19C, I4L, T5H, G22D, G18C, F19V) and also in P (E11Q, H13Y, H13T, I16T, P17L, R18G, T19P, P20L, A21L, R22V, V23L, T24Q, G25A, G26V, V27F, L29F, A38T, R110G, H122F, M124H, L129M, I135N, S135Y, S137T, Q139N, M145L, Y148F, K149F, Y148F, Y151L) which have not been described in previous studies. The results of the present investigation confirm the predominance of circulation of A/D/F genotypes in Brazil and in our Region. In addition, they confirm the presence of mutations in the HBV genome in treatment-naive patients or under the use of antiviral therapy. Therefore, these data contribute to knowledge regarding chronic HBV infection and reinforce the importance of molecular monitoring in infected patients.
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spelling Matos, Márcia Alves Diashttp://lattes.cnpq.br/0582530071710533Martins, Regina Maria BringelCarneiro, Megmar Aparecida dos SantosMatos, Márcia Alves Diashttp://lattes.cnpq.br/5486000603258410Santos, Norrama Araújo2019-05-08T13:06:12Z2019-03-19SANTOS, N. A. Caracterização molecular do vírus da hepatite B em pacientes cronicamente infectados em um centro de referência em Goiânia-GO. 2019. 160 f. Dissertação (Mestrado em Biologia da Relação Parasito-Hospedeiro) - Universidade Federal de Goiás, Goiânia, 2019.http://repositorio.bc.ufg.br/tede/handle/tede/9576ark:/38995/001300000664bGenotypes of hepatitis B virus and the occurrence of mutations in the genome may interfere with treatment response, disease progression to chronic form, cirrhosis and hepatocellular carcinoma. The objective of the present study was to analyze the molecular characteristics of HBV in patients with chronic hepatitis B in Goiânia-Goiás. Blood samples (N = 53) were collected from patients who were attended / followed at a referral hospital in Goiânia-Goiás. Initially, an interview was conducted with structured questionnaire on sociodemographic data, possible characteristics associated with the risk of HBV acquisition and previous vaccination against hepatitis B. Other information, such as clinical data, use of antiviral therapy and results of complementary tests were collected in the medical record and with the doctor in charge. All samples were screened for HBV serological markers (HBsAg, Anti-HBc, Anti-HBs, HBeAg and Anti-HBe) using commercial kits. Subsequently, viral DNA extraction and a semi- nested PCR were performed using primers complementary to the Pre-S / S (PS1, S2 / S22 and SR) and Pre-C / C (X1, C2, X4 and C3) regions of HBV. Then the samples were sequenced to the S and PreC / C regions of HBV for the determination of genotypes / subgenotypes and mutation screening. The nucleotide sequencing was performed in 22 samples, and the genotypes / subgenotypes A1 (n = 09), A2 (n = 01), D2 (n = 02), D3 (n = 07), and F2 were found. Mutations in the Pre C / C region (S171T, G1764A), region S (S45T, P46T, T114S, K122T, T123T, T143S, A159G, Y161F, I213L, L21S, T118A, V47G, P127L, F183C, M198I. Y206C, R24K, S61L, F8S, T127P, I68T, Y100C) and P region (I91L, Y126H, W153R, Y126R, V207L, L129M, Q130P) were identified and previously described in the literature, in patients with chronic hepatitis B. Furthermore, the presence of some nucleotide substitutions in the S regions (V47G, L42C, L14S, V14C, L15Y, Q16R, A17R, G44A, L49P, H61L, F158L, P178Q, F19C, I4L, T5H, G22D, G18C, F19V) and also in P (E11Q, H13Y, H13T, I16T, P17L, R18G, T19P, P20L, A21L, R22V, V23L, T24Q, G25A, G26V, V27F, L29F, A38T, R110G, H122F, M124H, L129M, I135N, S135Y, S137T, Q139N, M145L, Y148F, K149F, Y148F, Y151L) which have not been described in previous studies. The results of the present investigation confirm the predominance of circulation of A/D/F genotypes in Brazil and in our Region. In addition, they confirm the presence of mutations in the HBV genome in treatment-naive patients or under the use of antiviral therapy. Therefore, these data contribute to knowledge regarding chronic HBV infection and reinforce the importance of molecular monitoring in infected patients.Os genótipos do vírus da hepatite B e a ocorrência de mutações no genoma podem interferir na resposta ao tratamento, na progressão da doença para a forma crônica, cirrose e carcinoma hepatocelular. O objetivo do presente estudo foi analisar as características moleculares do HBV em pacientes com hepatite B crônica em Goiânia-Goiás. Amostras sanguíneas (N=53) foram colhidas de pacientes que eram atendidos/acompanhados em um hospital de referência em Goiânia. Inicialmente, foi realizada uma entrevista com questionário estruturado sobre dados sociodemográficos, possíveis características associadas ao risco de aquisição do HBV e vacinação prévia contra hepatite B. Outras informações, como dados clínicos, uso de terapia antiviral e resultados de exames complementares foram coletadas no prontuário e confirmadas com o médico responsável. Todas as amostras foram submetidas à pesquisa dos marcadores sorológicos do HBV (HBsAg, Anti-HBc, Anti-HBs, HBeAg e Anti-HBe) empregando-se kits comerciais. Posteriormente, foi realizada a extração do DNA viral e uma semi-nested PCR utilizando primers complementares às regiões Pré-S/S (PS1, S2/S22 e SR) e Pré-C/C (X1, C2, X4 e C3) do HBV. Em seguida, as amostras foram sequenciadas para as regiões S e Pré-C/C do HBV, para a determinação dos genótipos/subgenótipos e pesquisa de mutações. O sequenciamento dos nucleotídeos foi realizado em 22 amostras, e os genótipos/subgenótipos A1 (n = 09), A2 (n = 01), D2 (n = 02), D3 (n = 07), e F2 (n = 03) foram encontrados. Mutações na região Pré C/C (A1762T, G1764A), região S (S45T, P46T, T114S, K122R, P127T, T143S, A159G, Y161F, I213L, L21S, T118A, V47G, P127L, F183C, M198I, Y206C, R24K, S61L, F8S, T127P, I68T, Y100C) e região P (I91L, Y126H, W153R, Y126R, V207L, L129M, Q130P) foram identificadas, sendo estas previamente descritas na literarura, em pacientes com hepatite B crônica. Ainda, observou-se a presença de algumas alterações nas regiões S (V47G, L42P, L12C, L13S, V14C, L15Y, Q16R, A17R, G44A, L49P, H61L, F158L, P178Q, F19C, I4L, T5H, S6Q, G7D, G10D, G18C, F19V) e também na P (E11Q, H13Y, H13T, I14S, I16T, P17L, R18G, T19P, P20L, A21L, R22V, V23L, T24Q, G25A, G26V, V27F, L29F, A38T, I53T, T54H, R110G, H122F, M124H, I130V, D134N, S135Y, S137T, Q139N/M, M145L, Y148F, K149Q, Y148F, Y151L/F) que não foram descritas em estudos prévios. Os resultados da presente investigação ratificam a predominância de circulação dos genótipos A/D/F no Brasil e em nossa Região. Além disso, confirmam a presença de várias mutações no genoma do HBV em pacientes virgens de tratamento ou sob uso de terapia antiviral. Portanto, estes dados contribuem para o conhecimento a respeito da infecção crônica pelo HBV e reforçam a importância do acompanhamento molecular em pacientes infectados.Submitted by Ana Caroline Costa (ana_caroline212@hotmail.com) on 2019-05-06T18:23:46Z No. of bitstreams: 2 Dissertação - Norrama Araújo Santos - 2019.pdf: 4976352 bytes, checksum: 91a29e2d7c53de5bb807ae504d647fd9 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2019-05-08T13:06:12Z (GMT) No. of bitstreams: 2 Dissertação - Norrama Araújo Santos - 2019.pdf: 4976352 bytes, checksum: 91a29e2d7c53de5bb807ae504d647fd9 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)Made available in DSpace on 2019-05-08T13:06:12Z (GMT). No. of bitstreams: 2 Dissertação - Norrama Araújo Santos - 2019.pdf: 4976352 bytes, checksum: 91a29e2d7c53de5bb807ae504d647fd9 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2019-03-19application/pdfporUniversidade Federal de GoiásPrograma de Pós-graduação em Biologia da Relação Parasito-Hospedeiro (IPTSP)UFGBrasilInstituto de Patologia Tropical e Saúde Pública - IPTSP (RG)http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessHepatite B crônicaGenótiposMutaçõesChronic hepatitis BGenotypesMutationsBIOLOGIA E FISIOLOGIA DOS MICROORGANISMOS::VIROLOGIACaracterização molecular do vírus da hepatite B em pacientes cronicamente infectados em um centro de referência em Goiânia-GOMolecular characterization of hepatitis virus in patients chronically infected in a reference center in Goiânia-GOinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesis-5087190859350688984600600600-7769011444564556288-2817712778945337933reponame:Repositório Institucional da UFGinstname:Universidade Federal de Goiás (UFG)instacron:UFGLICENSElicense.txtlicense.txttext/plain; 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dc.title.eng.fl_str_mv Caracterização molecular do vírus da hepatite B em pacientes cronicamente infectados em um centro de referência em Goiânia-GO
dc.title.alternative.eng.fl_str_mv Molecular characterization of hepatitis virus in patients chronically infected in a reference center in Goiânia-GO
title Caracterização molecular do vírus da hepatite B em pacientes cronicamente infectados em um centro de referência em Goiânia-GO
spellingShingle Caracterização molecular do vírus da hepatite B em pacientes cronicamente infectados em um centro de referência em Goiânia-GO
Santos, Norrama Araújo
Hepatite B crônica
Genótipos
Mutações
Chronic hepatitis B
Genotypes
Mutations
BIOLOGIA E FISIOLOGIA DOS MICROORGANISMOS::VIROLOGIA
title_short Caracterização molecular do vírus da hepatite B em pacientes cronicamente infectados em um centro de referência em Goiânia-GO
title_full Caracterização molecular do vírus da hepatite B em pacientes cronicamente infectados em um centro de referência em Goiânia-GO
title_fullStr Caracterização molecular do vírus da hepatite B em pacientes cronicamente infectados em um centro de referência em Goiânia-GO
title_full_unstemmed Caracterização molecular do vírus da hepatite B em pacientes cronicamente infectados em um centro de referência em Goiânia-GO
title_sort Caracterização molecular do vírus da hepatite B em pacientes cronicamente infectados em um centro de referência em Goiânia-GO
author Santos, Norrama Araújo
author_facet Santos, Norrama Araújo
author_role author
dc.contributor.advisor1.fl_str_mv Matos, Márcia Alves Dias
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/0582530071710533
dc.contributor.referee1.fl_str_mv Martins, Regina Maria Bringel
dc.contributor.referee2.fl_str_mv Carneiro, Megmar Aparecida dos Santos
dc.contributor.referee3.fl_str_mv Matos, Márcia Alves Dias
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/5486000603258410
dc.contributor.author.fl_str_mv Santos, Norrama Araújo
contributor_str_mv Matos, Márcia Alves Dias
Martins, Regina Maria Bringel
Carneiro, Megmar Aparecida dos Santos
Matos, Márcia Alves Dias
dc.subject.por.fl_str_mv Hepatite B crônica
Genótipos
Mutações
topic Hepatite B crônica
Genótipos
Mutações
Chronic hepatitis B
Genotypes
Mutations
BIOLOGIA E FISIOLOGIA DOS MICROORGANISMOS::VIROLOGIA
dc.subject.eng.fl_str_mv Chronic hepatitis B
Genotypes
Mutations
dc.subject.cnpq.fl_str_mv BIOLOGIA E FISIOLOGIA DOS MICROORGANISMOS::VIROLOGIA
description Genotypes of hepatitis B virus and the occurrence of mutations in the genome may interfere with treatment response, disease progression to chronic form, cirrhosis and hepatocellular carcinoma. The objective of the present study was to analyze the molecular characteristics of HBV in patients with chronic hepatitis B in Goiânia-Goiás. Blood samples (N = 53) were collected from patients who were attended / followed at a referral hospital in Goiânia-Goiás. Initially, an interview was conducted with structured questionnaire on sociodemographic data, possible characteristics associated with the risk of HBV acquisition and previous vaccination against hepatitis B. Other information, such as clinical data, use of antiviral therapy and results of complementary tests were collected in the medical record and with the doctor in charge. All samples were screened for HBV serological markers (HBsAg, Anti-HBc, Anti-HBs, HBeAg and Anti-HBe) using commercial kits. Subsequently, viral DNA extraction and a semi- nested PCR were performed using primers complementary to the Pre-S / S (PS1, S2 / S22 and SR) and Pre-C / C (X1, C2, X4 and C3) regions of HBV. Then the samples were sequenced to the S and PreC / C regions of HBV for the determination of genotypes / subgenotypes and mutation screening. The nucleotide sequencing was performed in 22 samples, and the genotypes / subgenotypes A1 (n = 09), A2 (n = 01), D2 (n = 02), D3 (n = 07), and F2 were found. Mutations in the Pre C / C region (S171T, G1764A), region S (S45T, P46T, T114S, K122T, T123T, T143S, A159G, Y161F, I213L, L21S, T118A, V47G, P127L, F183C, M198I. Y206C, R24K, S61L, F8S, T127P, I68T, Y100C) and P region (I91L, Y126H, W153R, Y126R, V207L, L129M, Q130P) were identified and previously described in the literature, in patients with chronic hepatitis B. Furthermore, the presence of some nucleotide substitutions in the S regions (V47G, L42C, L14S, V14C, L15Y, Q16R, A17R, G44A, L49P, H61L, F158L, P178Q, F19C, I4L, T5H, G22D, G18C, F19V) and also in P (E11Q, H13Y, H13T, I16T, P17L, R18G, T19P, P20L, A21L, R22V, V23L, T24Q, G25A, G26V, V27F, L29F, A38T, R110G, H122F, M124H, L129M, I135N, S135Y, S137T, Q139N, M145L, Y148F, K149F, Y148F, Y151L) which have not been described in previous studies. The results of the present investigation confirm the predominance of circulation of A/D/F genotypes in Brazil and in our Region. In addition, they confirm the presence of mutations in the HBV genome in treatment-naive patients or under the use of antiviral therapy. Therefore, these data contribute to knowledge regarding chronic HBV infection and reinforce the importance of molecular monitoring in infected patients.
publishDate 2019
dc.date.accessioned.fl_str_mv 2019-05-08T13:06:12Z
dc.date.issued.fl_str_mv 2019-03-19
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
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dc.identifier.citation.fl_str_mv SANTOS, N. A. Caracterização molecular do vírus da hepatite B em pacientes cronicamente infectados em um centro de referência em Goiânia-GO. 2019. 160 f. Dissertação (Mestrado em Biologia da Relação Parasito-Hospedeiro) - Universidade Federal de Goiás, Goiânia, 2019.
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identifier_str_mv SANTOS, N. A. Caracterização molecular do vírus da hepatite B em pacientes cronicamente infectados em um centro de referência em Goiânia-GO. 2019. 160 f. Dissertação (Mestrado em Biologia da Relação Parasito-Hospedeiro) - Universidade Federal de Goiás, Goiânia, 2019.
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dc.publisher.none.fl_str_mv Universidade Federal de Goiás
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