Study of the prevalence of genotypes and resistance mutations associated with antiviral drugs in patients with chronic hepatitis B treated in reference services of Ceara state

Detalhes bibliográficos
Autor(a) principal: Josà NapoleÃo Monte da Cruz
Data de Publicação: 2015
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da UFC
Texto Completo: http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=15839
Resumo: Infection with hepatitis B virus (VHB) is a serious public health problem. An estimated 450 million chronic carriers worldwide, where at least 600,000 people die annually from diseases related to hepatitis B. Viral load, HBe seroconversion-antiHBe, and specific genotype and viral mutations are acquired factors influence the progression of the disease. The aim of this study was to investigate the prevalence of VHB resistance mutations associated with antiviral and evaluate the genotype distribution in a sample of 142 patients with chronic hepatitis B, treated in the State of Cearà referral hospitals. Patients were considered reactive serum HBsAg for at least six months. Serological tests were performed by electrochemiluminescence (EQL), ABBOTT laboratory for HBsAg, HBeAg and anti-HBe. The results of the serological screening showed that all samples: 142 (100%) were reactive serum HBsAg (IgG), 87 (61.0%) were negative to serum and serum HBeAg to anti-HBe reagent, 55 (39, 0%) are seroreactive for HBe and serum non-reactive for anti-HBe. The quantitation of viremia (viral load) was performed by real time PCR (QPCR) in LACEN-EC. The viral load varied between the limits (2067 IU / ml to 3.41 billion IU / ml), with a median of 70 403 IU / ml. Eighty-eight (62%) of all samples were submitted to analysis of mutations associated with treatment and genotyping the Hepatitis laboratory of the FIOCRUZ-RJ, screened for sequencing as quality criteria and routine laboratory biosafety this. The identification of genotypes in the population studied showed the following distribution: F: 47 (53.4%) of A: 34 (38.6%), the D: 4 (4.6%), E: 2 ( 2.3%) and G 1 (1.1%). And the following mutations were detected: L180M (n = 10 / 9.9%), M204V (n = 8 / 7.9%), M204I (n = 4/4%), G173L (n = 1/1%) , T169L (n = 1/1%), T184I (n = 1/1%), L80V (n = 1/1%) while 74.3% showed no change. In the study it was observed that the F genotype (53.4%) was the most prevalent in the research population of Indian origin, followed by genotype (38.6%) due to migration of African slaves. And, the higher frequency of the detected mutations are associated with nucleoside inhibitors and nucleotides, especially lamivudine.
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spelling info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisStudy of the prevalence of genotypes and resistance mutations associated with antiviral drugs in patients with chronic hepatitis B treated in reference services of Ceara stateEstudo da prevalÃncia dos genÃtipos e mutaÃÃes de resistÃncia associadas aos antivirais em pacientes com hepatite B crÃnica atendidos nos serviÃos de referÃncia do Estado do CearÃ2015-09-25Ivo Castelo Branco CoÃlho07442270387http://lattes.cnpq.br/8976612994194612Josà Milton de Castro Lima09161058300http://lattes.cnpq.br/4181709573316786Roberto da Justa Pires Neto44778309391http://lattes.cnpq.br/1887685326618139Elisabeth Lampe53343182753 http://lattes.cnpq.br/636390027036136901558404368http://lattes.cnpq.br/9252536254929988Josà NapoleÃo Monte da CruzUniversidade Federal do CearÃPrograma de PÃs-GraduaÃÃo em PatologiaUFCBRANATOMIA PATOLOGICA E PATOLOGIA CLINICAInfection with hepatitis B virus (VHB) is a serious public health problem. An estimated 450 million chronic carriers worldwide, where at least 600,000 people die annually from diseases related to hepatitis B. Viral load, HBe seroconversion-antiHBe, and specific genotype and viral mutations are acquired factors influence the progression of the disease. The aim of this study was to investigate the prevalence of VHB resistance mutations associated with antiviral and evaluate the genotype distribution in a sample of 142 patients with chronic hepatitis B, treated in the State of Cearà referral hospitals. Patients were considered reactive serum HBsAg for at least six months. Serological tests were performed by electrochemiluminescence (EQL), ABBOTT laboratory for HBsAg, HBeAg and anti-HBe. The results of the serological screening showed that all samples: 142 (100%) were reactive serum HBsAg (IgG), 87 (61.0%) were negative to serum and serum HBeAg to anti-HBe reagent, 55 (39, 0%) are seroreactive for HBe and serum non-reactive for anti-HBe. The quantitation of viremia (viral load) was performed by real time PCR (QPCR) in LACEN-EC. The viral load varied between the limits (2067 IU / ml to 3.41 billion IU / ml), with a median of 70 403 IU / ml. Eighty-eight (62%) of all samples were submitted to analysis of mutations associated with treatment and genotyping the Hepatitis laboratory of the FIOCRUZ-RJ, screened for sequencing as quality criteria and routine laboratory biosafety this. The identification of genotypes in the population studied showed the following distribution: F: 47 (53.4%) of A: 34 (38.6%), the D: 4 (4.6%), E: 2 ( 2.3%) and G 1 (1.1%). And the following mutations were detected: L180M (n = 10 / 9.9%), M204V (n = 8 / 7.9%), M204I (n = 4/4%), G173L (n = 1/1%) , T169L (n = 1/1%), T184I (n = 1/1%), L80V (n = 1/1%) while 74.3% showed no change. In the study it was observed that the F genotype (53.4%) was the most prevalent in the research population of Indian origin, followed by genotype (38.6%) due to migration of African slaves. And, the higher frequency of the detected mutations are associated with nucleoside inhibitors and nucleotides, especially lamivudine.A infecÃÃo pelo vÃrus da hepatite B (VHB) à um grave problema de saÃde pÃblica. Estimam-se em 450 milhÃes os portadores crÃnicos no mundo, em que pelo menos 600 mil pessoas morrem anualmente por doenÃas relacionadas com o vÃrus da hepatite B. A carga viral, soroconversÃo HBe â anti-HBe, genÃtipo e mutaÃÃes virais especÃficas e adquiridas sÃo fatores que influenciam a progressÃo dessa doenÃa. O objetivo do presente estudo foi investigar a prevalÃncia de mutaÃÃes de resistÃncia do VHB associada aos antivirais e avaliar a distribuiÃÃo genotÃpica numa amostragem de 142 pacientes com hepatite B crÃnica, atendidos nos hospitais de referÃncia do Estado do CearÃ. Foram realizadas sorologias por eletroquimioluminescÃncia (EQL), laboratÃrio ABBOTT para HBsAg, HBeAg e anti-HBe. O resultado da triagem sorolÃgica no total das amostras mostrou que: 142 (100%) foram sororeagentes para HBsAg (IgG), 87(61,0%) foram soro nÃo reagentes para HBeAg e soro reagentes para anti-HBe, 55(39,0%) sÃo soros reagentes para HBe e soro nÃo reagente para anti-HBe. A quantificaÃÃo da viremia (carga viral) foi realizada por PCR em tempo real (QPCR), no LACEN-CE. A carga viral variou entre os limites de (2.067 UI/mL a 3.410.000.000 UI/mL), com mediana de 70.403 UI/mL. Oitenta e oito (62%) do total das amostras foram submetidas à pesquisa de mutaÃÃes associadas ao tratamento e genotipagem no laboratÃrio de hepatites da FIOCRUZ-RJ, triadas para sequenciamento conforme critÃrios de qualidade e biosseguranÃa de rotina desse laboratÃrio. A identificaÃÃo dos genÃtipos na populaÃÃo estudada apresentou a seguinte distribuiÃÃo: F: 47 (53,4%), A: 34 (38,6%), D: 4(4,6%), E: 2(2,3%) e genÃtipo G: 1(1,1%). E as seguintes mutaÃÃes foram detectadas: L180M (n=10 / 9,9%), M204V (n=8 / 7,9%), M204I (n=4 / 4%), G173L (n=1 / 1%), T169L (n=1 / 1%), T184I (n=1 / 1%), L80V (n=1 / 1%) enquanto que 74,3% nÃo apresentaram mutaÃÃes. No estudo foi observado que o genÃtipo F(53,4%) foi o mais prevalente na populaÃÃo pesquisada de origem indÃgena, seguido do genÃtipo A (38,6%) devido à migraÃÃo de escravos africanos. E, que a maior frequÃncia das mutaÃÃes detectadas està associada a inibidores de nucleosÃdeos e nucleotÃdeos, principalmente a lamivudina.http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=15839application/pdfinfo:eu-repo/semantics/openAccessporreponame:Biblioteca Digital de Teses e Dissertações da UFCinstname:Universidade Federal do Cearáinstacron:UFC2019-01-21T11:29:11Zmail@mail.com -
dc.title.en.fl_str_mv Study of the prevalence of genotypes and resistance mutations associated with antiviral drugs in patients with chronic hepatitis B treated in reference services of Ceara state
dc.title.alternative.pt.fl_str_mv Estudo da prevalÃncia dos genÃtipos e mutaÃÃes de resistÃncia associadas aos antivirais em pacientes com hepatite B crÃnica atendidos nos serviÃos de referÃncia do Estado do CearÃ
title Study of the prevalence of genotypes and resistance mutations associated with antiviral drugs in patients with chronic hepatitis B treated in reference services of Ceara state
spellingShingle Study of the prevalence of genotypes and resistance mutations associated with antiviral drugs in patients with chronic hepatitis B treated in reference services of Ceara state
Josà NapoleÃo Monte da Cruz
ANATOMIA PATOLOGICA E PATOLOGIA CLINICA
title_short Study of the prevalence of genotypes and resistance mutations associated with antiviral drugs in patients with chronic hepatitis B treated in reference services of Ceara state
title_full Study of the prevalence of genotypes and resistance mutations associated with antiviral drugs in patients with chronic hepatitis B treated in reference services of Ceara state
title_fullStr Study of the prevalence of genotypes and resistance mutations associated with antiviral drugs in patients with chronic hepatitis B treated in reference services of Ceara state
title_full_unstemmed Study of the prevalence of genotypes and resistance mutations associated with antiviral drugs in patients with chronic hepatitis B treated in reference services of Ceara state
title_sort Study of the prevalence of genotypes and resistance mutations associated with antiviral drugs in patients with chronic hepatitis B treated in reference services of Ceara state
author Josà NapoleÃo Monte da Cruz
author_facet Josà NapoleÃo Monte da Cruz
author_role author
dc.contributor.advisor1.fl_str_mv Ivo Castelo Branco CoÃlho
dc.contributor.advisor1ID.fl_str_mv 07442270387
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/8976612994194612
dc.contributor.referee1.fl_str_mv Josà Milton de Castro Lima
dc.contributor.referee1ID.fl_str_mv 09161058300
dc.contributor.referee1Lattes.fl_str_mv http://lattes.cnpq.br/4181709573316786
dc.contributor.referee2.fl_str_mv Roberto da Justa Pires Neto
dc.contributor.referee2ID.fl_str_mv 44778309391
dc.contributor.referee2Lattes.fl_str_mv http://lattes.cnpq.br/1887685326618139
dc.contributor.referee3.fl_str_mv Elisabeth Lampe
dc.contributor.referee3ID.fl_str_mv 53343182753
dc.contributor.referee3Lattes.fl_str_mv http://lattes.cnpq.br/6363900270361369
dc.contributor.authorID.fl_str_mv 01558404368
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/9252536254929988
dc.contributor.author.fl_str_mv Josà NapoleÃo Monte da Cruz
contributor_str_mv Ivo Castelo Branco CoÃlho
Josà Milton de Castro Lima
Roberto da Justa Pires Neto
Elisabeth Lampe
dc.subject.cnpq.fl_str_mv ANATOMIA PATOLOGICA E PATOLOGIA CLINICA
topic ANATOMIA PATOLOGICA E PATOLOGIA CLINICA
dc.description.abstract.por.fl_txt_mv Infection with hepatitis B virus (VHB) is a serious public health problem. An estimated 450 million chronic carriers worldwide, where at least 600,000 people die annually from diseases related to hepatitis B. Viral load, HBe seroconversion-antiHBe, and specific genotype and viral mutations are acquired factors influence the progression of the disease. The aim of this study was to investigate the prevalence of VHB resistance mutations associated with antiviral and evaluate the genotype distribution in a sample of 142 patients with chronic hepatitis B, treated in the State of Cearà referral hospitals. Patients were considered reactive serum HBsAg for at least six months. Serological tests were performed by electrochemiluminescence (EQL), ABBOTT laboratory for HBsAg, HBeAg and anti-HBe. The results of the serological screening showed that all samples: 142 (100%) were reactive serum HBsAg (IgG), 87 (61.0%) were negative to serum and serum HBeAg to anti-HBe reagent, 55 (39, 0%) are seroreactive for HBe and serum non-reactive for anti-HBe. The quantitation of viremia (viral load) was performed by real time PCR (QPCR) in LACEN-EC. The viral load varied between the limits (2067 IU / ml to 3.41 billion IU / ml), with a median of 70 403 IU / ml. Eighty-eight (62%) of all samples were submitted to analysis of mutations associated with treatment and genotyping the Hepatitis laboratory of the FIOCRUZ-RJ, screened for sequencing as quality criteria and routine laboratory biosafety this. The identification of genotypes in the population studied showed the following distribution: F: 47 (53.4%) of A: 34 (38.6%), the D: 4 (4.6%), E: 2 ( 2.3%) and G 1 (1.1%). And the following mutations were detected: L180M (n = 10 / 9.9%), M204V (n = 8 / 7.9%), M204I (n = 4/4%), G173L (n = 1/1%) , T169L (n = 1/1%), T184I (n = 1/1%), L80V (n = 1/1%) while 74.3% showed no change. In the study it was observed that the F genotype (53.4%) was the most prevalent in the research population of Indian origin, followed by genotype (38.6%) due to migration of African slaves. And, the higher frequency of the detected mutations are associated with nucleoside inhibitors and nucleotides, especially lamivudine.
A infecÃÃo pelo vÃrus da hepatite B (VHB) à um grave problema de saÃde pÃblica. Estimam-se em 450 milhÃes os portadores crÃnicos no mundo, em que pelo menos 600 mil pessoas morrem anualmente por doenÃas relacionadas com o vÃrus da hepatite B. A carga viral, soroconversÃo HBe â anti-HBe, genÃtipo e mutaÃÃes virais especÃficas e adquiridas sÃo fatores que influenciam a progressÃo dessa doenÃa. O objetivo do presente estudo foi investigar a prevalÃncia de mutaÃÃes de resistÃncia do VHB associada aos antivirais e avaliar a distribuiÃÃo genotÃpica numa amostragem de 142 pacientes com hepatite B crÃnica, atendidos nos hospitais de referÃncia do Estado do CearÃ. Foram realizadas sorologias por eletroquimioluminescÃncia (EQL), laboratÃrio ABBOTT para HBsAg, HBeAg e anti-HBe. O resultado da triagem sorolÃgica no total das amostras mostrou que: 142 (100%) foram sororeagentes para HBsAg (IgG), 87(61,0%) foram soro nÃo reagentes para HBeAg e soro reagentes para anti-HBe, 55(39,0%) sÃo soros reagentes para HBe e soro nÃo reagente para anti-HBe. A quantificaÃÃo da viremia (carga viral) foi realizada por PCR em tempo real (QPCR), no LACEN-CE. A carga viral variou entre os limites de (2.067 UI/mL a 3.410.000.000 UI/mL), com mediana de 70.403 UI/mL. Oitenta e oito (62%) do total das amostras foram submetidas à pesquisa de mutaÃÃes associadas ao tratamento e genotipagem no laboratÃrio de hepatites da FIOCRUZ-RJ, triadas para sequenciamento conforme critÃrios de qualidade e biosseguranÃa de rotina desse laboratÃrio. A identificaÃÃo dos genÃtipos na populaÃÃo estudada apresentou a seguinte distribuiÃÃo: F: 47 (53,4%), A: 34 (38,6%), D: 4(4,6%), E: 2(2,3%) e genÃtipo G: 1(1,1%). E as seguintes mutaÃÃes foram detectadas: L180M (n=10 / 9,9%), M204V (n=8 / 7,9%), M204I (n=4 / 4%), G173L (n=1 / 1%), T169L (n=1 / 1%), T184I (n=1 / 1%), L80V (n=1 / 1%) enquanto que 74,3% nÃo apresentaram mutaÃÃes. No estudo foi observado que o genÃtipo F(53,4%) foi o mais prevalente na populaÃÃo pesquisada de origem indÃgena, seguido do genÃtipo A (38,6%) devido à migraÃÃo de escravos africanos. E, que a maior frequÃncia das mutaÃÃes detectadas està associada a inibidores de nucleosÃdeos e nucleotÃdeos, principalmente a lamivudina.
description Infection with hepatitis B virus (VHB) is a serious public health problem. An estimated 450 million chronic carriers worldwide, where at least 600,000 people die annually from diseases related to hepatitis B. Viral load, HBe seroconversion-antiHBe, and specific genotype and viral mutations are acquired factors influence the progression of the disease. The aim of this study was to investigate the prevalence of VHB resistance mutations associated with antiviral and evaluate the genotype distribution in a sample of 142 patients with chronic hepatitis B, treated in the State of Cearà referral hospitals. Patients were considered reactive serum HBsAg for at least six months. Serological tests were performed by electrochemiluminescence (EQL), ABBOTT laboratory for HBsAg, HBeAg and anti-HBe. The results of the serological screening showed that all samples: 142 (100%) were reactive serum HBsAg (IgG), 87 (61.0%) were negative to serum and serum HBeAg to anti-HBe reagent, 55 (39, 0%) are seroreactive for HBe and serum non-reactive for anti-HBe. The quantitation of viremia (viral load) was performed by real time PCR (QPCR) in LACEN-EC. The viral load varied between the limits (2067 IU / ml to 3.41 billion IU / ml), with a median of 70 403 IU / ml. Eighty-eight (62%) of all samples were submitted to analysis of mutations associated with treatment and genotyping the Hepatitis laboratory of the FIOCRUZ-RJ, screened for sequencing as quality criteria and routine laboratory biosafety this. The identification of genotypes in the population studied showed the following distribution: F: 47 (53.4%) of A: 34 (38.6%), the D: 4 (4.6%), E: 2 ( 2.3%) and G 1 (1.1%). And the following mutations were detected: L180M (n = 10 / 9.9%), M204V (n = 8 / 7.9%), M204I (n = 4/4%), G173L (n = 1/1%) , T169L (n = 1/1%), T184I (n = 1/1%), L80V (n = 1/1%) while 74.3% showed no change. In the study it was observed that the F genotype (53.4%) was the most prevalent in the research population of Indian origin, followed by genotype (38.6%) due to migration of African slaves. And, the higher frequency of the detected mutations are associated with nucleoside inhibitors and nucleotides, especially lamivudine.
publishDate 2015
dc.date.issued.fl_str_mv 2015-09-25
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
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dc.publisher.none.fl_str_mv Universidade Federal do CearÃ
dc.publisher.program.fl_str_mv Programa de PÃs-GraduaÃÃo em Patologia
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publisher.none.fl_str_mv Universidade Federal do CearÃ
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