Análise multivariada de variáveis relacionadas ao fluxo biliar e sobrevida pós-Kasai em pacientes com atresia biliar / Multivariate analysis of biliary flow-related factors and post-kasai survival in biliary atresia patients

ABSTRACT BACKGROUND: Biliary atresia represents the most common surgically treatable cause of cholestasis in newborns. If not corrected, secondary biliary cirrhosis invariably results. OBJECTIVE: To evaluate, through multivariate analysis, the prognostic factors associated with the presence of biliary flow and survival with the native liver following Kasai portoenterostomy. METHODS: The study analyzed data from 117 biliary atresia patients who underwent portoenterostomy and had suitable histological material for evaluation. A logistic regression model was used to assess the presence of biliary flow. Survival was investigated through Kaplan-Meier curves and Cox-adjusted models. RESULTS: One third of patients achieved biliary flow and the median age at surgery was 81 days. Age at surgery, albumin, postoperative complications, biliary atresia structural malformation (BASM), liver architecture, larger duct diameter at porta hepatis, and cirrhosis (Ishak score) were the initial variables for the multivariate analysis. Age at surgery >90 days was the only variable associated with the absence of biliary drainage. Survival analysis revealed that the absence of biliary flow (P<0.0001), age at surgery >90 days (P=0.035), and the presence of BASM (P<0.0001), alone, could predict death or need for liver transplantation. Multivariate analysis demonstrated that the absence of biliary flow (P<0.0001 hazard ratio [HR] 6.25, 95% confidence interval [CI] 3.19-12.22) and the presence of BASM (P=0.014 HR 2.16, 95% CI 1.17-3.99) were associated with lowest survival with the native liver. CONCLUSION: Age at surgery >90 days was associated with absence of biliary flow. The presence of biliary drainage and the absence of structural malformations are cornerstone features for higher survival rates with the native liver.

RESUMO CONTEXTO: A atresia biliar representa a principal causa de colestase tratada cirurgicamente durante o período neonatal. Se a criança não for operada, ela evolui invariavelmente para cirrose biliar secundária. OBJETIVO: Avaliar, através de análise multivariada, os fatores prognósticos associados à presença de fluxo biliar e à sobrevida com fígado nativo após a realização da portoenterostomia de Kasai. MÉTODOS: O estudo analisou 117 pacientes com atresia biliar submetidos à portoenterostomia e com material histológico adequado para avaliação. O modelo de regressão logística foi utilizado para avaliar a presença de fluxo biliar. Sobrevida foi estudada através das curvas Kaplan-Meier e ajuste do modelo de Cox. RESULTADOS: Um terço dos pacientes obteve fluxo biliar e a mediana de idade à cirurgia foi de 81 dias. Idade à cirurgia, albumina, complicação pós-operatória, BASM (do inglês, biliary atresia structural malformation), arquitetura hepática, diâmetro do maior canalículo no porta hepatis e cirrose, segundo o escore de Ishak, foram as variáveis iniciais da análise multivariada. Idade à cirurgia maior que 90 dias de vida foi a única variável associada à ausência de drenagem biliar. A análise de sobrevida mostrou que as variáveis: ausência de fluxo biliar (P<0,0001), idade à cirurgia maior que 90 dias (P=0,035) e presença de BASM (P<0,0001), isoladamente, predizem morte ou necessidade de transplante hepático. Na análise multivariada, ausência de fluxo biliar (P<0,0001 HR:6,25 [IC95% 3,19; 12,22]) e presença de BASM (P=0,014 HR:2,16 [IC95% 1,17; 3,99]) mostraram-se associadas, com significância estatística, a menor sobrevida com fígado nativo. CONCLUSÃO: Idade à cirurgia maior que 90 dias foi identificada como fator de risco independente para ausência de fluxo biliar. Além disso, a presença de drenagem biliar e a ausência de malformações estruturais da atresia biliar são variáveis fundamentais para a maior sobrevida com fígado nativo.

Current management of biliary atresia based on 35 years of experience at a single center

OBJECTIVE: The prognosis of patients with biliary atresia undergoing Kasai portoenterostomy is related to the timing of the diagnosis and the indication for the procedure. The purpose of the present study is to present a practical flowchart based on 257 children who underwent Kasai portoenterostomy. METHODS: We conducted a retrospective cohort study of patients who underwent Kasai portoenterostomy between 1981 and 2016. RESULTS: During the first period (1981 to 2009), 230 infants were treated, and the median age at the time of surgery was 84 days; jaundice was resolved in 77 patients (33.5%). During the second period, from 2010 to 2016, a new diagnostic approach was adopted to shorten the wait time for portoenterostomy; an ultrasonography examination suggestive of the disease was followed by primary surgical exploration of the biliary tract without complementary examination or liver biopsy. Once the diagnosis of biliary atresia was confirmed, a portoenterostomy was performed during the same surgery. During this period, 27 infants underwent operations; the median age at the time of surgery was 66 days (p<0.001), and jaundice was resolved in 15 patients (55.6% - p=0.021), with a survival rate of the native liver of 66.7%. CONCLUSION: Primary surgical exploration of the biliary tract without previous biopsy was effective at improving the prognostic indicators of patients with biliary atresia undergoing Kasai portoenterostomy.

Pregnancy in biliary atresia after kasai operation complicated by portal hypertension.

Hepatic portoenterostomy or Kasai operation has been widely accepted as the standard therapy for biliary atresia. Recently, more female patients have grown up and reached adulthood; therefore, pregnancy in women with biliary atresia is sometimes inevitable. The authors report a 17-year-old woman with biliary atresia post Kasai operation at 3 months of age. After the operation, she became jaundice-free but developed portal hypertension with abnormal liver function. She had several episodes of esophageal variceal bleeding and was treated by beta-blocker and endoscopic sclerotherapy. Since then, she was lost to follow up for nearly 2 years. She came back again with 12 weeks of gestation with no symptoms of gastrointestinal bleeding for antenatal care. At 32 weeks of gestation, she presented with severe hematemesis from variceal bleeding and had thrombocytopenia from hypersplenism. She was treated with somatostatin analogue, fluid and blood component replacement and other supportive treatments. Cesarean section was performed when she was stable at 33 weeks of gestation. After the operation, her clinical status was improved and had no other complications. Her baby experienced complications of prematurity but improved after treatment. Pregnancy may affect the natural course of portal hypertension and worsen the clinical outcome. Pregnancy should be avoided in patients with portal hypertension, however it is not contraindicated. Pregnancy in biliary atresia patients needs intensive prenatal care.

Avaliação da funçäo mitocondrial hepática em crianças portadoras de colestase neonatal / Evaluation of hepatic mitocondrial function in infants with neonatal cholestasis

A dificuldade em se excluir o diagnóstico de atresia de vias biliares através de exames não invasivos freqüentemente leva à realização de biópsia hepática, cirúrgica ou transparietal. Apesar de inúmeros estudos a respeito de muitos de seus aspectos, esta moléstia ainda é considerada idiopática. Com a finalidade de compreender melhor as alterações hepáticas decorrentes da atresia de vias biliares, estudamos a função mitocondrial dos hepatócitos em crianças portadoras de colestase neonatal. Foram estudadas dez crianças portadoras de colestase neonatal, das quais sete foram submetidas à laparotomia para realização de biópsia hepática, colangiografia intra-operatória e portoenterostomia. Os valores obtidos para o consumo de oxigênio no estado 3 de ativação mitocondrial foram semelhantes aos de fígados normais, o que reflete uma boa capacidade de oxidação/fosforilação, transformando ADP em ATP. Estes resultados revelam uma capacidade compensatória mitocondrial para enfrentar a situação adversa conseqüente à doença hepática. Os valores para o estado 4 foram significativamente maiores que os de fígados normais, o que indica um aumento de permeabilidade de membrana mitocondrial. A diminuição do potencial de membrana, com lesão do tipo desacoplamento oxidação/fosforilação também sugere deficiência na capacidade energética dos hepatócitos. A diminuição da razão de controle respiratório foi outro achado significativo, que pode ser parte da alteração típica de colestase neonatal crônica, com algum grau de cirrose biliar.

Use of appendix in biliary atresia.

Antiperistaltic appendiceal conduit based on its vascular pedicle was used as hepaticoporto-appendico-jejunostomy (HAJ) in 9 infants with advanced stage of biliary atresia. Operative procedure was simple and less time consuming. The postoperative cholangitis was conspicuously absent, possibly due to the role played by the presence of lymphoid follicles in the wall of the appendix. Our early experience with this technique shows that antiperistaltic appendiceal conduit works quite satisfactorily. The procedure has been successfully utilised to reduce the problems contributing post-operative morbidity and mortality in cases with the advanced disease. The HAJ procedure provides a conduit for bilioenteric drainage, that closely resembles to normal anatomy.