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Abstract(s)
Introdução: A colestase neonatal, apesar de ser uma doença com baixa incidência
mundial, apresenta uma elevada taxa de mortalidade se não for identificada e tratada
de forma precoce. A colestase neonatal é classificada em dois grupos etiológicos
distintos: colestase extra-hepática e colestase intra-hepática. Esta é uma distinção
crucial, uma vez que a etiologia da colestase vai influenciar a escolha do tratamento. A
análise da biópsia hepática percutânea é a principal ferramenta de diagnóstico na
avaliação inicial de um lactente colestático, demonstrando os níveis de acurácia mais
elevados quando comparado com os restantes métodos de diagnósticos utilizados para
este fim. Este estudo teve como objetivo fazer uma extensa revisão bibliográfica da
avaliação histopatológica da colestase neonatal, e uma análise histopatológica de
amostras de lactentes colestáticos de forma a correlacionar as variáveis
histopatológicas com o diagnóstico etiológico final e avaliar a acurácia da biópsia
hepática percutânea.
Materiais e métodos: Quarenta e sete biópsias hepáticas (27 biópsias em cunha e 20
biópsias percutâneas) obtidas entre 2006 e 2021 de pacientes com colestase neonatal
tratados no Serviço de Pediatria do Hospital de Clínicas de Porto Alegre foram
estudadas prospectivamente através de um protocolo histopatológico específico. Foram
utilizadas pelo menos 3 colorações diferentes e estudadas 18 variáveis histopatológicas
hepáticas relacionadas com diagnóstico diferencial da colestase neonatal. Este
protocolo histopatológico foi desenvolvido e usado em consenso por 2 experts em
histopatologia hepática, acompanhados pelo mestrando. Todo o processo foi feito de
forma cega em relação à história clínica, aos resultados de imagem, aos dados
laboratoriais e ao diagnóstico final dos pacientes. As alterações histopatológicas
avaliadas nos pacientes pediátricos com colestase neonatal foram divididas em 32
fatores relacionados e foram analisados por regressão logística.
Resultados: A Reação Ductular (p<0.001), a Proliferação de vasos no espaço porta e
pontes fibrosas (p<0.001), e o Padrão obstrutivo (p<0.001) foram os melhores
indicadores de Atresia Biliares. A associação entre as variáveis “Padrão Obstrutivo” e
“Proliferação de vasos no espaço porta e pontes fibrosas” apresenta uma acurácia de
76,6% no diagnóstico de Atresia Biliar. A sensibilidade e a especificidade da biópsia
hepática para o diagnóstico de Atresia Biliar, utilizando o nosso modelo, foi de 71,4% e
80,8%, respetivamente. Conclusão: A identificação da “Proliferação de vasos no espaço porta e pontes
fibrosas” constitui uma variável adicional às varáveis atualmente consideradas de
“Padrão obstrutivo”, acrescentando desta forma acurácia na diferenciação
histopatológica entre a Atresia Biliar e colestase intra-hepática. No entanto, o
diagnóstico diferencial da colestase neonatal continua a ser desafiador e deve incluir,
de forma complementar à avaliação histopatológica, uma correlação clínica adequada e
estudos genéticos.
Introduction: Neonatal cholestasis, despite having low incidence worldwide, presents a health burden with elevated mortality rate if not early identified and treated. Neonatal cholestasis is broadly classified in two etiological groups: extrahepatic mechanical obstructive and intrahepatic cholestasis. This is a crucial distinction, since has precise therapeutic implications. The analysis of a percutaneous liver biopsy is a main diagnostic tool in the initial evaluation of a cholestatic infant, presenting the highest levels of accuracy among the diagnostic methods employed for this purpose. This study aimed to do an extensive bibliographic review of the histopathological evaluation of neonatal cholestasis, and a histopathological analysis of the samples of cholestatic infants to correlate the histopathological variables with the final etiological diagnosis and assessed the accuracy of percutaneous liver biopsy. Materials and Methods: Forty-seven liver biopsies (27 wedge biopsies and 20 percutaneous biopsies), all from patients cared for neonatal cholestasis in the Pediatrics Service of Hospital de Clínicas de Porto Alegre from 2006 to 2021 were prospectively studied using a specifically designed histopathological protocol. At least 3 different stains were used, and 18 hepatic histopathological variables related to the differential diagnosis of neonatal cholestasis were studied. This histopathological protocol was developed and then used by 2 hepatic’s histopathology experts and the M.D student, blinded for the clinical history, imaging results, laboratory data or final diagnosis of each case. The histopathological changes analysed in pediatric patients with neonatal cholestasis were divided into 32 related factors and evaluated by logistic regression analyses. Results: Ductular proliferation (p<0.001), Vascular proliferation in the portal tracts and fibrous bridges (p<0.001), and Obstructive pattern (p<0.001) were the most accurate variable for the diagnosis of Biliary Atresia. The association between the variable “Obstructive pattern” and “Vascular Proliferation in portal tracts and fibrous bridges” had an accuracy of 76,6% for the diagnosis of Biliary Atresia. Sensitivity and specificity of liver biopsy for diagnosing Biliary Atresia was 71,4% and 80,8%, respectively. Conclusion: The variable “Vascular proliferation in portal tracts and fibrous bridges” added accuracy to the presence of an “Obstructive pattern” in the histopathological differentiation between Biliary Atresia and intrahepatic cholestatic diseases. The differential diagnosis, however, remains challenging and must include proper clinical correlation and genetic studies.
Introduction: Neonatal cholestasis, despite having low incidence worldwide, presents a health burden with elevated mortality rate if not early identified and treated. Neonatal cholestasis is broadly classified in two etiological groups: extrahepatic mechanical obstructive and intrahepatic cholestasis. This is a crucial distinction, since has precise therapeutic implications. The analysis of a percutaneous liver biopsy is a main diagnostic tool in the initial evaluation of a cholestatic infant, presenting the highest levels of accuracy among the diagnostic methods employed for this purpose. This study aimed to do an extensive bibliographic review of the histopathological evaluation of neonatal cholestasis, and a histopathological analysis of the samples of cholestatic infants to correlate the histopathological variables with the final etiological diagnosis and assessed the accuracy of percutaneous liver biopsy. Materials and Methods: Forty-seven liver biopsies (27 wedge biopsies and 20 percutaneous biopsies), all from patients cared for neonatal cholestasis in the Pediatrics Service of Hospital de Clínicas de Porto Alegre from 2006 to 2021 were prospectively studied using a specifically designed histopathological protocol. At least 3 different stains were used, and 18 hepatic histopathological variables related to the differential diagnosis of neonatal cholestasis were studied. This histopathological protocol was developed and then used by 2 hepatic’s histopathology experts and the M.D student, blinded for the clinical history, imaging results, laboratory data or final diagnosis of each case. The histopathological changes analysed in pediatric patients with neonatal cholestasis were divided into 32 related factors and evaluated by logistic regression analyses. Results: Ductular proliferation (p<0.001), Vascular proliferation in the portal tracts and fibrous bridges (p<0.001), and Obstructive pattern (p<0.001) were the most accurate variable for the diagnosis of Biliary Atresia. The association between the variable “Obstructive pattern” and “Vascular Proliferation in portal tracts and fibrous bridges” had an accuracy of 76,6% for the diagnosis of Biliary Atresia. Sensitivity and specificity of liver biopsy for diagnosing Biliary Atresia was 71,4% and 80,8%, respectively. Conclusion: The variable “Vascular proliferation in portal tracts and fibrous bridges” added accuracy to the presence of an “Obstructive pattern” in the histopathological differentiation between Biliary Atresia and intrahepatic cholestatic diseases. The differential diagnosis, however, remains challenging and must include proper clinical correlation and genetic studies.
Description
Keywords
Atresia Biliar Biópsia Hepática Colestase Neonatal Diagnóstico Diferencial Histopatologia