Extrahepatic biliary atresia: current concepts and future directions

OBJETIVOS: Apresentar uma revisão atualizada sobre atresia das vias biliares extra-hepáticas, com ênfase em etiopatogenia, abordagens diagnósticas e terapêuticas e prognóstico. FONTES DOS DADOS: Foram selecionadas pelos sites de busca médica (MEDLINE e PubMed) pesquisas relacionadas à atresia biliar, utilizando as seguintes palavras-chave: biliary atresia,etiopathogenesis, diagnosis, treatment, prognosis, children. SíNTESE DOS DADOS A atresia das vias biliares extra-hepáticas é a principal indicação de transplante hepático na faixa etária pediátrica. Quanto à etiologia, o citomegalovírus, o reovírus e o rotavírus têm sido os agentes mais estudados como possíveis desencadeadores da obstrução imunomediada da árvore biliar. A resposta imune, especialmente o predomínio da resposta TH1 e do interferon gama, a susceptibilidade genética e as alterações do desenvolvimento embrionário da árvore biliar são aspectos que podem participar na etiopatogênese da obliteração das vias biliares extra-hepáticas. Ainda hoje, o único tratamento disponível é a portoenterostomia, cujos resultados são melhores quando realizada nos primeiros 2 meses de vida. Em relação ao prognóstico, as crianças não tratadas vão a óbito na totalidade, por complicações relacionadas à hipertensão portal e à cirrose hepática, e mesmo os casos tratados necessitam, em sua maioria, do transplante hepático. CONCLUSÃO: A atresia das vias biliares extra-hepáticas continua sendo a principal indicação de transplante hepático em crianças, e a mudança deste panorama depende de um melhor entendimento da etiopatogenia da obstrução biliar nos diferentes fenótipos da doença. Investigações futuras a respeito do papel do interferon gama e de outras citocinas são necessárias para avaliar se esses aspectos seriam potenciais alvos de intervenção terapêutica.

OBJECTIVE: To provide an updated review on extrahepatic biliary atresia, focusing mainly on its etiopathogenesis, diagnosis, treatment and prognosis. SOURCES: MEDLINE and PubMed databases were searched using the following keywords: biliary atresia,etiopathogenesis, diagnosis, treatment, prognosis, children. SUMMARY OF THE FINDINGS: Extrahepatic biliary atresia is the main indication for liver transplantation among pediatric patients. As to its etiology, cytomegalovirus, reovirus and rotavirus have been widely investigated as possible triggers of the immunomediated obstruction of the biliary tree. The immune response, especially the predominant TH1 and interferon-gamma responses, genetic susceptibility and disorders related to the embryonic development of the biliary tree can play a role in the etiopathogenesis of extrahepatic biliary atresia. Yet today, portoenterostomy is the only available treatment, with better results when performed in the first 2 months of life. As to prognosis, all untreated children eventually die due to complications resulting from portal hypertension and liver cirrhosis, and most treated children have to undergo liver transplantation. CONCLUSIONS: Extrahepatic biliary atresia is still the major indication for pediatric liver transplantation, and to change this scenario some more light should be shed upon the etiopathogenesis of biliary atresia in different disease phenotypes. Future research into the role of interferon-gamma and of other cytokines is necessary in order to assess whether these aspects should be potential targets for therapeutic intervention.

Kinetic effects of trimethoprim-sulfamethoxazole in children with biliary atresia: a new dosing regimen

Pharmacokinetics for combination trimethoprim/sulfamethoxazole (TMP/SMX) was studied in only four patients with biliary atresia (BA): three girls, 6.2, 8.0 and 8.2 years of age and one boy 8.4 years of age, as this is an uncommon obstructive anomaly of the extrahepatic biliary system and has been described as having a poor prognosis. These four patients are the survivors of 27 initial children who were operated on previously. They have been receiving 2.3 ñ 0.5 mg/kg TMP, and 11.5 ñ2.6 mg/kg SMX every 12 h since 2 weeks after surgical treatment for biliary atresia performed at 2 - 2.5 months of age. The patients have suffered some episodes of cholangitis during their short lives, most of them after interrupting temporally the chemotherapy. Nevertheless, they have a achieved a favorable quality of life. TMP/SMX disposition was well characterized by a one compartment open pharmacokinetic model. Wide interpatient variability was observed for all pharmacokinetic parameters with coefficients of variation for t½ el, ClT, and Vd of 33.2, 49.6, and 26.3 per cent, respectively, for SMX and 108.9, 52.1, and 71.0 per cent, respectively, for TMP. A marked difference in the pharmacokinetics of TMP and SMX was observed, for example; (ClT: mean ñ SD; 90.3 ñ 47.0 ml/kg/g for TMP and 13.7 ñ 6.8 ml/kg/h for SMX), (t½ el with 7.93 ñ 8.64 h for TMP and 10.51 ñ 3.49 h for SMX). In order to develop dosage schedules that would reliably achieve peak serum concentrations of TMP/SMX in the therapeutic range, we found that established dose leads to high fluctuations at steady state between Cmax, ss and Cmin, ss, without maintaining therapeutic levels. Recommended maintenance dose varied from 8 to 30 mg/kg for SMX with a mean of 21.9 ñ 10.89 mg/kg/12 h, and from 0.8 to 4.5 mg/kg/12 h with a mean of 3.2 ñ 1.7 mg/kg/12 h. The present study illustrattes the need for pharmacokinetic studies for the individualization of drug dosing in patients with BA

Extrahepatic biliary atresia

Extrahepatic biliary atresia is a disease of unknown cause, leading to profound cholestasis and progressive biliary cirrhosis. This paper discusses the diagnosis and management of this condition. It is stressed that bile flow can be established in 80-90% of infants referred to surgery within 60 days afterbirth, Liver transplantation is essential for infants who are referred late [120 days of age or later]; those whose initial portoenterostomy was not successful, and those who develop end-stage liver disease in spite of bile drainage

Análisis del tratamiento quirúrgico en atresia de vía biliar

Se analizó el tratamiento quirúrgico de ocho pacientes con diagnostico de atresia de vías biliares en el hospital de Niños Baca Ortiz entre julio de 1991 a julio de 1993. Tres pacientes que tenían menos de 70 días de edad, fueron sometidos a cirugía, dos con técnica de Kasai, uno con técnica de Ueda; logrando obtener eliminación de bilis al tubo digestivo. Con la técnica de Ueda, hobo más complicaciones que con la de Kasai, como desequilibrio hidroelectrolítico, gasto elevado de bilis, etc. En los pacientes mayores a 70 dias solo se realizó biopsia hepática a cielo abierto, estos pacientes fallecieron por cirrosis secundaria a atresia de vías biliares. Se concluye que el método quirúrgico idoneo para el tratamiento de atresia de vías biliares es el de Kasai, el pronóstico depende de la edad del paciente, el tipo de cirugía realizada, estadío histológico del parenquima hepático, la frecuencia de colangitis y la presencia o no de canaliculos biliares.

Atresia de las vías biliares / Biliary tract atresia

Los recientes avances en el manejo de este problema quirúrgico han cambiado por completo el grave pronóstico que antiguamente se le atribuía. El artículo revisa conceptos actuales en Atresia Biliar y presenta las últimas cifras del Registro Americano de Atresia Biliar