Fatores relacionados à resposta ao tratamento na hepatite autoimune

Detalhes bibliográficos
Autor(a) principal: Ludmila Resende Guedes
Data de Publicação: 2019
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da UFMG
Texto Completo: http://hdl.handle.net/1843/32327
Resumo: Background: Autoimmune hepatitis (AIH) is a rare disease with a complex and not fully understood pathogenesis. Prognostic factors that might influence treatment response, relapse rates, transplantation needs and death are not well established. The major aim of the study is to investigate possible markers associated with response to immunosuppression. Other goals are to evaluate the epidemiologic profile of patients with AIH, considering the severity of presentation, mortality rates, transplant needs, relapse and the predictors modifying these outcomes. Methods: This is an observational study with a retrospective evaluation of a longitudinal cohort. 102 patients were selected at the Hepatology Ambulatory of Federal University of Minas Gerais’ Hospital from 1990-2018, from both sexes, that fulfilled criteria of possible or definite diagnosis of AIH and that were given immunosuppressant. Overlap syndromes were excluded. Pretreatment data as such as clinical profile, laboratory and histological exams were analyzed with regard to biochemical response in one year, histological remission, transplantation, relapse and death. Statistical analysis were done by Mann-Whitney´s U test, Student´s T test, chi-square and further by logistic regression. Kaplan Meier´s survival graphic was performed to evaluate overall survival and transplant-free survival, applying Cox regression when necessary. The fixed p level was 5%. Results: The biochemical and histological remission rates were similar to other Brazilian studies, although different from international literature. Cirrhosis was present in 59% at diagnosis and reduced biochemical response rate in one year in 73,7%. Increments in age was associated with a higher rate of cirrhosis at presentation. There were no significant predictors of histological remission. 6% underwent liver transplant in a median of time of 9.4 years from the diagnosis. Biochemical response was an important protective factor regarding transplantation, reducing the risk in 86%. Overall survival was 89% and 4 patients died in 340 months. Ascites at presentation, associated with higher AST/ALT relation and MELD, increased the risk of death in 20 times. Conclusion: AIH prognosis is directly influenced by distinguished characteristics of each population studied. Multi-centric studies would be necessary to identify non-invasive markers or clinical scores in order to predict the probability of different outcomes with a relevant impact on the accurate disease management.
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spelling Fatores relacionados à resposta ao tratamento na hepatite autoimuneFeatures related to treatment response in autoimune hepatitisHepatite autoimuneCirrose hepáticaPrognósticoTransplante hepáticoHepatite AutoimuneCirrose HepáticaPrognósticoTransplante de FígadoBackground: Autoimmune hepatitis (AIH) is a rare disease with a complex and not fully understood pathogenesis. Prognostic factors that might influence treatment response, relapse rates, transplantation needs and death are not well established. The major aim of the study is to investigate possible markers associated with response to immunosuppression. Other goals are to evaluate the epidemiologic profile of patients with AIH, considering the severity of presentation, mortality rates, transplant needs, relapse and the predictors modifying these outcomes. Methods: This is an observational study with a retrospective evaluation of a longitudinal cohort. 102 patients were selected at the Hepatology Ambulatory of Federal University of Minas Gerais’ Hospital from 1990-2018, from both sexes, that fulfilled criteria of possible or definite diagnosis of AIH and that were given immunosuppressant. Overlap syndromes were excluded. Pretreatment data as such as clinical profile, laboratory and histological exams were analyzed with regard to biochemical response in one year, histological remission, transplantation, relapse and death. Statistical analysis were done by Mann-Whitney´s U test, Student´s T test, chi-square and further by logistic regression. Kaplan Meier´s survival graphic was performed to evaluate overall survival and transplant-free survival, applying Cox regression when necessary. The fixed p level was 5%. Results: The biochemical and histological remission rates were similar to other Brazilian studies, although different from international literature. Cirrhosis was present in 59% at diagnosis and reduced biochemical response rate in one year in 73,7%. Increments in age was associated with a higher rate of cirrhosis at presentation. There were no significant predictors of histological remission. 6% underwent liver transplant in a median of time of 9.4 years from the diagnosis. Biochemical response was an important protective factor regarding transplantation, reducing the risk in 86%. Overall survival was 89% and 4 patients died in 340 months. Ascites at presentation, associated with higher AST/ALT relation and MELD, increased the risk of death in 20 times. Conclusion: AIH prognosis is directly influenced by distinguished characteristics of each population studied. Multi-centric studies would be necessary to identify non-invasive markers or clinical scores in order to predict the probability of different outcomes with a relevant impact on the accurate disease management.Introdução: A hepatite autoimune (HAI) é uma doença relativamente rara, complexa, cuja patogênese não é completamente compreendida. Fatores prognósticos que possam influenciar a resposta ao tratamento, as taxas de recidiva e evolução para transplante e óbito ainda não estão bem estabelecidos. O presente estudo visa primariamente investigar marcadores clínicos, laboratoriais e histológicos associados à resposta ao tratamento imunossupressor da HAI. Objetiva-se, ainda, avaliar o perfil epidemiológico dos pacientes com HAI nesta população, considerando a gravidade de apresentação da doença, taxa de mortalidade e necessidade de transplante hepático, bem como identificar marcadores de fibrose e cirrose à apresentação, de resposta bioquímica ou histológica incompletas, além de fatores associados a recidiva após a suspensão do tratamento e de preditores de transplante e óbito. Métodos: Trata-se de um estudo observacional, com avaliação retrospectiva de uma coorte longitudinal. Foram incluídos 102 pacientes atendidos no Ambulatório de Hepatologia do Hospital das Clínicas da UFMG no período entre 1990 e 2018, de ambos os sexos, que preenchiam critérios de diagnóstico provável ou definitivo de HAI de acordo com o GIHAI e que foram submetidos a terapia imunossupressora. Presença de síndrome de sobreposição com outras hepatopatias autoimunes foi fator de exclusão. Os dados coletados foram: sexo, idade ao diagnóstico, tipo da HAI, presença de hepatopatia associada e uso de álcool. Ao diagnóstico, foram avaliados presença de cirrose e complicações, FIB-4, Child-Pugh, MELD, plaquetas, AST, ALT, relação AST/ALT, FA, GGT, RNI, albumina, bilirrubina total, ASMA, Anti-LKM1, ANA, IgG, gamaglobulinas, além dos graus de atividade e fibrose obtidos na primeira biopsia hepática dos pacientes. Os desfechos avaliados foram: remissão bioquímica em 1 ano, remissão histológica, realização de transplante hepático, recidiva e óbito. A relação entre as variáveis e os desfechos foi analisada inicialmente por meio dos testes U de Mann-Whitney, teste T de Student, qui-quadrado e posteriormente por regressão logística. Foram realizadas curvas de sobrevida pelo método de Kaplan-Meier para avaliação da sobrevida geral e da sobrevida livre de transplante, com aplicação da regressão de Cox quando adequada. O nível de significância foi fixado em 5%. Resultados: As taxas de remissão bioquímica e histológica foram de 55,7% e 30,3%, semelhantes à casuística brasileira, no entanto menores em relação à literatura internacional. A cirrose ao diagnóstico esteve presente em 59% da amostra e reduziu a chance de resposta bioquímica em 1 ano em 73,7%. Elevação da idade aumentou a chance de cirrose ao diagnóstico. Não houve identificação de preditores de resposta histológica. O percentual de transplante hepático foi de 6% com uma mediana de tempo de 9,0 anos desde o diagnóstico. A remissão bioquímica em 1 ano foi fator protetor de realização de transplante hepático em 86%. A sobrevida ao final do acompanhamento máximo de 340 meses foi de 89%, com ocorrência de 4 óbitos no período. A presença de ascite ao diagnóstico, associada a maior relação AST/ALT e MELD, aumentou em 20 vezes a chance de evolução para óbito. Conclusão: O prognóstico da HAI é influenciado diretamente pelas distintas características clínicas de cada população estudada. Estudos multicêntricos seriam relevantes na identificação de marcadores não invasivos e/ou escores clínicos a fim de predizer a probabilidade dos desfechos, com importante impacto no manejo adequado da doença.Outra AgênciaUniversidade Federal de Minas GeraisBrasilMED - DEPARTAMENTO DE CLÍNICA MÉDICAPrograma de Pós-Graduação em Ciências Aplicadas à Saúde do AdultoUFMGCláudia Alves Coutohttp://lattes.cnpq.br/1218114023294729Eduardo Luiz Rachid CançadoMaria de Lourdes de Abreu FerrariLuciana Diniz SilvaFrancisco Guilherme Cancela e PennaLudmila Resende Guedes2020-02-03T15:48:48Z2020-02-03T15:48:48Z2019-03-28info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/1843/32327porinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMG2020-02-04T06:24:38Zoai:repositorio.ufmg.br:1843/32327Repositório InstitucionalPUBhttps://repositorio.ufmg.br/oairepositorio@ufmg.bropendoar:2020-02-04T06:24:38Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false
dc.title.none.fl_str_mv Fatores relacionados à resposta ao tratamento na hepatite autoimune
Features related to treatment response in autoimune hepatitis
title Fatores relacionados à resposta ao tratamento na hepatite autoimune
spellingShingle Fatores relacionados à resposta ao tratamento na hepatite autoimune
Ludmila Resende Guedes
Hepatite autoimune
Cirrose hepática
Prognóstico
Transplante hepático
Hepatite Autoimune
Cirrose Hepática
Prognóstico
Transplante de Fígado
title_short Fatores relacionados à resposta ao tratamento na hepatite autoimune
title_full Fatores relacionados à resposta ao tratamento na hepatite autoimune
title_fullStr Fatores relacionados à resposta ao tratamento na hepatite autoimune
title_full_unstemmed Fatores relacionados à resposta ao tratamento na hepatite autoimune
title_sort Fatores relacionados à resposta ao tratamento na hepatite autoimune
author Ludmila Resende Guedes
author_facet Ludmila Resende Guedes
author_role author
dc.contributor.none.fl_str_mv Cláudia Alves Couto
http://lattes.cnpq.br/1218114023294729
Eduardo Luiz Rachid Cançado
Maria de Lourdes de Abreu Ferrari
Luciana Diniz Silva
Francisco Guilherme Cancela e Penna
dc.contributor.author.fl_str_mv Ludmila Resende Guedes
dc.subject.por.fl_str_mv Hepatite autoimune
Cirrose hepática
Prognóstico
Transplante hepático
Hepatite Autoimune
Cirrose Hepática
Prognóstico
Transplante de Fígado
topic Hepatite autoimune
Cirrose hepática
Prognóstico
Transplante hepático
Hepatite Autoimune
Cirrose Hepática
Prognóstico
Transplante de Fígado
description Background: Autoimmune hepatitis (AIH) is a rare disease with a complex and not fully understood pathogenesis. Prognostic factors that might influence treatment response, relapse rates, transplantation needs and death are not well established. The major aim of the study is to investigate possible markers associated with response to immunosuppression. Other goals are to evaluate the epidemiologic profile of patients with AIH, considering the severity of presentation, mortality rates, transplant needs, relapse and the predictors modifying these outcomes. Methods: This is an observational study with a retrospective evaluation of a longitudinal cohort. 102 patients were selected at the Hepatology Ambulatory of Federal University of Minas Gerais’ Hospital from 1990-2018, from both sexes, that fulfilled criteria of possible or definite diagnosis of AIH and that were given immunosuppressant. Overlap syndromes were excluded. Pretreatment data as such as clinical profile, laboratory and histological exams were analyzed with regard to biochemical response in one year, histological remission, transplantation, relapse and death. Statistical analysis were done by Mann-Whitney´s U test, Student´s T test, chi-square and further by logistic regression. Kaplan Meier´s survival graphic was performed to evaluate overall survival and transplant-free survival, applying Cox regression when necessary. The fixed p level was 5%. Results: The biochemical and histological remission rates were similar to other Brazilian studies, although different from international literature. Cirrhosis was present in 59% at diagnosis and reduced biochemical response rate in one year in 73,7%. Increments in age was associated with a higher rate of cirrhosis at presentation. There were no significant predictors of histological remission. 6% underwent liver transplant in a median of time of 9.4 years from the diagnosis. Biochemical response was an important protective factor regarding transplantation, reducing the risk in 86%. Overall survival was 89% and 4 patients died in 340 months. Ascites at presentation, associated with higher AST/ALT relation and MELD, increased the risk of death in 20 times. Conclusion: AIH prognosis is directly influenced by distinguished characteristics of each population studied. Multi-centric studies would be necessary to identify non-invasive markers or clinical scores in order to predict the probability of different outcomes with a relevant impact on the accurate disease management.
publishDate 2019
dc.date.none.fl_str_mv 2019-03-28
2020-02-03T15:48:48Z
2020-02-03T15:48:48Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/1843/32327
url http://hdl.handle.net/1843/32327
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidade Federal de Minas Gerais
Brasil
MED - DEPARTAMENTO DE CLÍNICA MÉDICA
Programa de Pós-Graduação em Ciências Aplicadas à Saúde do Adulto
UFMG
publisher.none.fl_str_mv Universidade Federal de Minas Gerais
Brasil
MED - DEPARTAMENTO DE CLÍNICA MÉDICA
Programa de Pós-Graduação em Ciências Aplicadas à Saúde do Adulto
UFMG
dc.source.none.fl_str_mv reponame:Repositório Institucional da UFMG
instname:Universidade Federal de Minas Gerais (UFMG)
instacron:UFMG
instname_str Universidade Federal de Minas Gerais (UFMG)
instacron_str UFMG
institution UFMG
reponame_str Repositório Institucional da UFMG
collection Repositório Institucional da UFMG
repository.name.fl_str_mv Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)
repository.mail.fl_str_mv repositorio@ufmg.br
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