Atresia biliar por citomegalovirus: un reporte de caso / Cytomegalovirus-associated biliary atresia: Case report

Resumen La atresia biliar asociada con inmunoglobulina M (IgM) positiva para citomegalovirus (CMV) es una entidad infrecuente que se caracteriza por la obliteración inflamatoria progresiva de los conductos intra- o extrahepáticos producida por una reacción autoinmune perinatal contra el CMV. El diagnóstico se realiza con IgM positiva para CMV y biopsia hepática con evidencia de atresia de las vías biliares. El conocimiento y la identificación temprana de esta patología conduce a un manejo quirúrgico temprano, mejorando considerablemente el pronóstico de estos pacientes. Se presenta un caso clínico de una paciente de 82 días de edad con un cuadro de acolia, coluria e ictericia de inicio tardío, asociado con hiperbilirrubinemia a expensas de la directa, elevación de perfil hepático e IgM positiva para CMV. La colangiorresonancia intraoperatoria confirmó el cuadro de atresia de las vías biliares. Se realizó una derivación biliodigestiva tipo Kasai y la toma de biopsia hepática que confirmó el cuadro clínico.

Abstract Biliary atresia associated with positive cytomegalovirus IgM results is a rare condition characterized by progressive inflammatory obliteration of the intra- or extrahepatic ducts. It is caused by a perinatal autoimmune reaction against cytomegalovirus (CMV). Diagnosis is made based on positive IgM for CMV and liver biopsy with evidence of bile duct atresia. Knowledge and timely identification of this disease leads to early surgical management, considerably improving the prognosis of these patients. This is the clinical case of an 82-day-old female patient with late-onset acholia, choluria, and jaundice, associated with conjugated hyperbilirubinemia, elevated liver function tests and positive CMV IgM results. Intraoperative cholangioresonance confirmed bile duct atresia. The Kasai procedure was performed, and a liver biopsy was taken, confirming the diagnosis.

Guía de práctica clínica en atresia de las vías biliares / Clinical practice guidelines in biliary atresia

Basada en la mejor evidencia científica disponible, se presenta la guía de práctica clínica en atresia de vías biliares, la cual se define como una obstrucción progresiva de las vías biliares intra- o extrahepáticas en recién nacidos y lactantes pequeños y causa ictericia colestásica grave y cirrosis hepática. Es una enfermedad poco frecuente, de etiología desconocida, con mayor incidencia en países asiáticos. Clínicamente se expresa por ictericia obstructiva, acolia, coluria y hepatoesplenomegalia. Los complementarios expresan una hiperbilirrubinemia directa con aumento de las enzimas hepáticas, y el diagnóstico se confirma en nuestro hospital con la colangiografía, generalmente en el curso de una laparoscopía. El tratamiento es quirúrgico y consiste en la portoenterostomía de Kasai, con mejores resultados en cuanto al drenaje biliar si se realiza antes de los 60 días de vida, así como el trasplante hepático. La enfermedad tiene un curso progresivo hacia la cirrosis hepática en etapas tempranas de la vida, sobre todo si no se realiza el diagnóstico y tratamiento quirúrgico precozmente, con implicaciones en la supervivencia y calidad de vida de estos pacientes. Por tanto, referir precozmente al paciente con sospecha de atresia de vías biliares a un centro especializado es la piedra angular de la actitud médica. La presente guía de práctica clínica pretende ofrecer las herramientas técnicas estandarizadas para mejorar los resultados a los pacientes con esta enfermedad, así como contribuir con la docencia y las investigaciones(AU)

Based on the best scientific evidence available, it is presented the clinical practice guidelines on biliary atresia. This disease is defined as a progressive obstruction of the intra and/or extrahepatic bile ducts in newborns and young infants, causing severe cholestatic jaundice and cirrhosis of the liver. It is a rare disease of unknown etiology, with a higher incidence in Asian countries. It is clinically expressed by obstructive jaundice, acholia, choluria and hepatosplenomegaly. Laboratory tests show a direct hyperbilirubin and elevated liver enzymes, and in our hospital, the diagnosis is confirmed by a cholangiography, usually during a laparoscopy procedure. It has surgical treatment and it involves a Kasai portoenterostomy, with better results regarding biliary drainage if it is performed before 60 days of life, as well as liver transplant. This condition has a progressive course towards liver cirrhosis in early stages of life, mainly if the diagnosis and surgical treatment are not made timely, with implications for the survival and quality of life of these patients. Therefore, early referral of the patient with suspected biliary atresia to a specialized center is the cornerstone of the medical attitude. This clinical practice guidelines aims to offer standardized technical tools to improve the outcome for patients with this disease, as well as to contribute to teaching and research(AU)

Atresia de vías biliares extrahepaticas en pediatria y citomegalovirus como causante / Extrahepatic biliary atresia in pediatrics and cytomegalovirus as a cause

La atresia de vías biliares es una alteración con gran importancia clínica, más frecuente en la primera infancia, se caracteriza por la obliteración proliferativa de los conductos biliares que progresa a fibrosis hepática, cirrosis e insuficiencia hepática en etapa terminal. El objetivo es presentar un caso clínico inusual y conocer la forma de actuar ante un caso similar. Se trata de paciente femenino de 4 meses de edad, con piel y mucosas ictéricas - verdosas, con hígado palpable debajo del reborde costal derecho, bazo palpable debajo del reborde costal izquierdo. Serología para Citomegalovirus positivo. La ecografía abdominal reporto: Atresia de vías biliares. Se indicó una portoenterostomia de Kasai, sin embargo por la edad de la paciente, el procedimiento quirúrgico no se realizó. La atresia de vías biliares es una patología poco frecuente, su etiología es desconocida, pero es importante saber reconocerla durante los primeros 2 meses de vida, para evitar complicaciones.

Biliary Atresia is a disorder with great clinical importance more frequent in early childhood, characterized by proliferative obliteration of the bile ducts that progresses to liver fibrosis, cirrhosis and end stage liver failure. The objective is to present an unusual clinical case and to know how to act in such a case. It is a female patient of 4 months of age, with icteric skin and mucosa - greenish, with palpable liver below the right costal ridge, palpable spleen below the left costal ridge. Serology for Cytomegalovirus positive.Abdominal ultrasound reported: Biliary Atresia A portoenterostomy of Kasai was indicated, however due to the age of the patient, the surgical procedure was not performed. Biliary Atresia is a rare disease, its etiology is unknown, but it is important to recognize it during the first 2 months of life, to avoid complications.

Trasplante hepático infantil: necesidad del país, normativa y legislación para priorizar a los pacientes pediátricos / Pediatric liver transplant, need of country, normative and legislation to prioritize pediatric patient

El Ecuador no contaba con un programa de trasplante hepático infantil y fue un problema para las autoridades de salud. Como alternativa de tratamiento se implementó un sistema de deriva-ción internacional para que los pacientes hayan accedido al trasplante en centros calificados, con la modalidad del donante vivo relacionado. Se logró acreditar en el 2019 en la ciudad de Cuenca, el primer programa de trasplante infantil para generar un cambio importante en el sis-tema de atenciones, pero fue necesario dejar clara todas las normas y regulaciones que involu-cren la prioridad de éstos pacientes y los aspectos técnicos quirúrgicos que han implicado la uti-lización de éste tipo de procedimientos como: split, hígado reducido y donante vivo relacionado.

Ecuador did not have a child liver transplant program and was a problem for health authorities. As an alternative treatment, an international referral system was implemented so that the patients had access to the transplant in qualified centers, with the modality of the living donor related. It was possible to accredit in 2019 in the city of Cuenca, the first child transplant program to generate a major change in the care system, but it was necessary to make clear all the rules and regulations that involve the priority of these patients and the technical aspects Surgical that have involved the use of these types of procedures such as: split, reduced liver and related living donor.

Correlación de los hallazgos de anatomía patológica y la sobrevida en los pacientes con atresia de vias biliares en los últimos diez años / Correlation of pathology, anatomy findings and survival in patients with biliary atresia during the past ten years

La atresia de vías biliares es una colangiopatía obstructiva neonatal1 caracterizada por cambios obstructivos progresivos tanto de la vía intra como extra hepática. El objetivo de este estudio fue correlacionar los hallazgos de la biopsia hepática y la sobrevida de los pacientes de atresia de vías biliares desde el 2004 hasta el 2014 en los Hospitales Pediátrico Baca Ortiz y Metropolitano de Quito. Es un estudio transversal analítico, en el que se incluyeron a 11 pacientes pediátricos. Los resultados obtenidos revelan que el sexo masculino fue el más afectado con histopatología no favorable. El grupo de edad fue de 1 mes hasta 4 meses, predominó el tipo III de atresia de vías biliares. Se encontró que hay un patrón de atresia de vías biliares como fibrosis, concreciones biliares, y ductulitis que tiene una evolución favorable. Sin embargo sí se encuentra además de lo citado células gigantes, degeneración plumosa esto revelaría signos de patrón no favorable. El patrón de biopsia favorable fue más frecuente en el sexo femenino, con nivel de albumina de 3,6 g/dl, bilirrubinas de 8,2 mg/dl. En el patrón de biopsia no favorable el sexo masculino fue más afectado, con niveles promedio de albúmina de 2,8 g/dl y bilirrubinas de 10,2 mg/dl. Las pruebas de función hepática (ALT, AST, GGT) tuvieron más de 2 DS y no hubo relación con los patrones estudiados. Los pacientes sometidos al procedimiento de Kasai tuvieron complicaciones como la colangitis en el 63,8% de los casos, no relacionándose con el patrón de la biopsia hepática. La sobrevida fue del 63,6%

Bile duct atresia is a neonatal obstructive cholangiopathy1 characterize by progressive obstructive changes of both intra and extra hepatic pathways. The objective of this study was to correlate pathology, anatomy and survival in patients with biliary atresia during the period from 2004 to 2014 in the Pediatric Hospital Baca Ortiz and Metropolitano Hospital of Quito. This is a cohort longitudinal study. That includes 11 pediatrics patients whose cases met the inclusion criterion. Results show that males were more affected and they have an unfavorable histopalothogy. The age group was from 1 to 4 months and type III biliary atresia was predominant. It was found that there is a pattern of biliary atresia as fibrosis, concretions and ductulitis that have favorable evolution but if there are gigant cells, this indicates a poor prognosis. The favorable histopathological pattern was more frequent in females, with albumin level of 3.6g/dl, and bilirubin of 8.2mg/dl. Males were more frequently affected by an unfavorable patern. They presented an average albumin level of 2.8 g/dl, whith avarege level of albúmina 2,8g/dl and bilirubin of 10.2 mg/dl. Liver function tests (ALT, AST, GGT) had more than 2 SD and there was no relation to the patterns studied. The patients who were exposed to the Kasai procedure had complications such as cholangitis in 63.8%, not being related to the pattern of liver biopsy. Survival was 63.6%.

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.

Patrón clínico y epidemiológico de la atresia de vías biliares en Cuba / Clinical and epidemiological pattern of biliary atresia in Cuba

Introducción: La atresia de vías biliares es una colangiopatía infrecuente que se presenta en recién nacidos entre la segunda y cuarta semana de vida. Objetivo: Determinar el patrón clínico-epidemiológico de la atresia de vías biliares en Cuba. Método: Estudio descriptivo en la población con atresia de vías biliares(n= 30) atendida en el Hospital William Soler (enero 2011-diciembre 2015). Se midieron los rasgos clínicos, humorales y variables epidemiológicas con análisis de incidencia (por 1 000 nacidos vivos) y pruebas estadísticas con significación para plt;0,05). Resultados: La incidencia en Cuba es de 0,47x 10 000 nacidos vivos (1: 21 078 nacidos vivos), en Mayabeque, la más alta con 1: 6 784. Todos tuvieron ictericia y 96,7 por ciento coluria. Se presentaron concentraciones elevadas de bilirrubina total (media= 184,9 µmol/L), ligera elevación de alaninoaminotransferasa (media= 201,8 U/L) y aspartatoaminotransferasa (media= 279,5 U/L), mayor aumento en la concentración de gammaglutamiltransferasa (media= 588 U/L) que de fosfatasa alcalina (media=1 557,1 u/L) e incremento del colesterol (6,8 mmol/L) con triglicéridos normales. El 70 por ciento de los sometidos a intervención quirúrgica antes de los 60 días de nacido restablecieron el flujo biliar contra 35,5 por ciento que no lo lograron cuando se intervinieron posteriormente. Conclusiones: La incidencia en la enfermedad en Cuba asciende, sin preferencia de género y es superior en Mayabeque. Son típicas las manifestaciones de ictericia, coluria, hiperbilirrubinemia, hipertransaminasemia ligera, hipercolesterolemia con alteración de gammaglutamiltransferasa más que de la fosfatasa alcalina y restablecimiento del flujo biliar en operados antes de los 60 días de nacido(AU)

Introduction: Biliary atresia is an infrequent colangiopaty that it is present in newborns among the second and the forth weeks of life. Objective: To determine the clinical and epidemiological pattern of biliary atresia in Cuba. Method: Descriptive study in the population presenting biliary atresia (n= 30) attended in William Soler Hospital (from January, 2011 to December, 2015). Clinical and humoral features, and epidemiological variables were measured by an incidence analysis (per 1 000 live births) and statistical tests with significance of p<0,05. Results: Incidence in Cuba is of 0.47 x 10 000 live births (1: 21 078 live births); in Mayabeque province, it is registered the highest incidence 1: 6 784. All the patients presented icterus and 96.7 percent presented choluria. High concentrations of total bilirubine (mean= 184.9 µmol/L), slight increase of alaninoaminotransferasa (mean= 201.8 U/L) and aspartatoaminotransferasa (mean= 27.5 U/L) than in the alcaline fosfatase (mean= 1 557.1 U/L); and cholesterol increase (6.8 mmol/L) with normal triglycerides were present. 70 percent of the patients that underwent surgeries before reaching 60 days of life could reestablish the biliar flow. 35 percent did not achieve this while underwent a surgery after 60 days of life. Conclusions: The incidence of this disease is increasing in Cuba, not having gender preferences and it is higher in Mayabeque province. Manifestations of icterus, choluria, hyperbilirubinemia, light hypertransaminasemia, hypercholesterolemia with gammaglutamiltransferasa alteration higher than alcaline fosfatase, and the reestablishment of the biliary flow in patients being operated before the 60 days of life, are common(AU)

Uso de la tarjeta colorimétrica visual para la detección oportuna de atresia de vías biliares / Colorimetric card use for early detection visual biliary atresia

Resumen: Introducción: La atresia de vías biliares (AVB) es una condición que provoca obstrucción al flujo biliar, y de no corregirse quirúrgicamente, provoca cirrosis y la muerte antes de los 2 años de edad. En México, a partir del año 2013 se incorporó la tarjeta colorimétrica visual (TCV) para la detección oportuna de la AVB a la Cartilla Nacional de Salud (CNS). El objetivo de este estudio fue evaluar el impacto de la TCV para la detección de AVB antes y después de su incorporación a la CNS. Métodos: Estudio ambispectivo, observacional y analítico. Se incluyeron pacientes con AVB atendidos en dos hospitales pediátricos de tercer nivel de atención. Se compararon la edad de referencia, el diagnóstico y la cirugía antes y después de la incorporación de la TCV. Además, se realizó un cuestionario a los padres para conocer su percepción sobre la TCV. Resultados: En 59 niños no hubo diferencias en la edad al diagnóstico (75 vs 70 días) ni en la edad al momento de la cirugía (84 vs 90 días) entre antes y después de la implementación de la TCV. Solo el 30% de los padres recibieron información del uso de la TCV y solo el 38% identificaron las evacuaciones anormales. Conclusiones: Este estudio no mostró cambios en el tiempo para la detección oportuna de AVB mediante el uso de la TCV. Por lo tanto, es necesario reforzar el programa en los tres niveles de atención en nuestro país.

Abstract: Background: Bile duct atresia (BVA) is a condition that causes obstruction to biliary flow, not corrected surgically, causes cirrhosis and death before 2 years of age. In Mexico from 2013 the visual colorimetric card (VVC) was incorporated for the timely detection of BVA to the National Health Card (NHC). The aim of this study was to evaluate the impact of VCT for the detection of BVA before and after the use of NHC incorporation. Methods: Ambispective, analytical observational study. We included patients with AVB treated in two pediatric hospitals of third level care. We compared the age of reference, diagnosis and surgery before and after incorporation of the TCV. In addition, a questionnaire was made to the parents to know their perception about the TCV. Results: In 59 children, there were no differences in age at diagnosis (75 vs 70 days) and age at surgery (84 vs 90 days) between the pre and post-implementation period of the VVC. The questionnaire showed that 10 (30%) of the parents received information about the use of the VVC and 13 (38%) identified the abnormal evacuations. Conclusions: This study did not show changes in time for the timely detection of BVA by using VVC. Therefore, it is necessary to reinforce the program in the three levels of care in our country.

Hallazgos por imagen en pacientes con atresia de vías biliares en el Hospital de Especialidades Carlos Andrade Marín en el período de enero 2016 - marzo 2017 / Imaging findings in patients with biliary atresia in Carlos Andrade Marín Specialties Hospital, in the period between Jan 2016-Mar 2017

Introducción. Revisión de los hallazgos clínicos y radiológicos de la atresia de la vía biliar, una anomalía del desarrollo biliar que tiene un riesgo alto de mortalidad por las complicaciones asociadas si no se la corrige oportunamente. Material y métodos. Serie de siete casos reportados en el Hospital de Especialidades Carlos Andrade Marín en el periodo enero 2016 a marzo 2017, seis mujeres y un varón, todos con cuadro clínico de ictericia prolongada, acolia, patrón de colestasis, hallazgos por imagen y biopsias sugestivas de atresia de vías biliares. Resultados. Todos los pacientes presentaron ictericia y coluria, en exámenes de laboratorio patrón colestásico en todos los pacientes, en los estudios de imagen el hallazgo predominante en sospecha de atresia de vías biliares fue la ausencia de la vesícula biliar y el signo del cordón triangular solamente en tres pacientes, en la biopsia hepática todos mostraron algún grado de fibrosis hepática. Discusión. La atresia de la vía biliar es una enfermedad compleja y grave, en nuestra serie de casos se confirma la utilidad del ultrasonido como método de diagnóstico de atresia de vías biliares ya que es un método mucho más accesible que la resonancia magnética que generalmente tiene menor disponibilidad y mayor costo. Conclusión. El ultrasonido abdominal es una herramienta extremadamente valiosa en sospecha clínica de atresia de vías biliares, debe realizarse un diagnóstico oportuno para mejorar el pronóstico de los pacientes.

Introduction. This is a review of clinical and radiological findings of biliary atresia, an anomaly of biliary tree development that carries a high risk of mortality due to complications unless they are corrected in a short time. Materials and methods. We reviewed a series of seven cases reported at Carlos Andrade Marín Specialties Hospital, from January 2016 to March 2017. Six women and one male were followed. All of them showed clinical signs such as long term jaundice, cholestasis, as well as, imaging findings and liver biopsies, suggesting biliary tract atresia. Results. All patients presented jaundice and choluria, in laboratory tests a cholestasic pattern in all of them, in the imaging studies the predominant finding in suspicion of biliary atresia was the absence of gallbladder and the triangular cord sign in only three patients, in the liver biopsy all of them showed some degree of liver fibrosis. Discussion. Bile duct atresia is a complex and serious disease. In our case serie we confirmed the utility of ultrasound as diagnosis method in biliary duct atresia, is more available than magnetic resonance which is more expensive and less available in different centers. Conclusion. Abdominal ultrasound is an extremely valuable tool in clinical suspicion of biliary atresia, a timely diagnosis must be made to improve patient´s prognosis.

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.

IL-6, TNF-α, IL-10, and nutritional status in pediatric patients with biliary atresia / IL-6, TNF-α, IL-10 e estado nutricional em pacientes pediátricos com atresia biliar

Abstract Objectives: The objective of the present study is to evaluate whether IL-6, TNF-α, IL-10 are associated with nutritional status in patients with cirrhosis secondary to biliary atresia and compare to healthy controls. Methods: The parameters used for nutritional assessment were the standard deviation scores of height-for-age and of triceps skinfold thickness-for-age. The severity of cirrhosis was evaluated using the Child-Pugh score and PELD/MELD. Serum cytokines were measured using Cytometric Bead Array flow cytometry. Results: IL-6, TNF-α, and IL-10 were significantly higher in the cirrhosis group when compared with the control group (2.4 vs. 0.24 (p < 0.001), 0.21 vs. 0.14 (p = 0.007), and 0.65 vs. 0.36 (p = 0.004), respectively. IL-6 and IL-10 were positively correlated with disease severity (0.450 [p = 0.001] and 0.410; [p = 0.002], respectively). TNF-α did not show a significant correlation with disease severity (0.100; p = 0.478). Regarding nutritional evaluation, IL-6 was negatively correlated with the standard deviation score of height-for-age (−0.493; p < 0.001) and of triceps skinfold thickness-for-age (−0.503; p < 0.001), respectively. IL-10 exhibited a negative correlation with the standard deviation score of height-for-age (−0.476; p < 0.001) and the standard deviation score of triceps skinfold thickness-for-age (−0.388; p = 0.004). TNF-α did not show any significance in both anthropometric parameters (−0.083 (p = 0.555) and −0.161 (p = 0.253). Conclusion: The authors suggest that, in patients with cirrhosis secondary to biliary atresia, IL-6 could be used as a possible supporting biomarker of deficient nutritional status and elevated IL-10 levels could be used as a possible early-stage supporting biomarker of deteriorating nutritional status.

Resumo Objetivos: Avaliar se há associações entre a IL-6, o TNF-α, a IL-10 e a estado nutricional em pacientes com cirrose secundária a atresia biliar e comparar com controles saudáveis. Métodos: Os parâmetros usados na avaliação nutricional foram desvio padrão de estatura para a idade e espessura da prega cutânea do tríceps para a idade. A gravidade da cirrose foi avaliada por meio da classificação de Child-Pugh e do PELD/MELD. As citocinas no soro foram medidas por citometria de fluxo - técnica de Cytometric Bead Array. Resultados: A IL-6, o TNF-α e a IL-10 foram significativamente maiores no grupo de cirrose em comparação com o grupo de controle [2,4 em comparação com 0,24 (p < 0,001)], [0,21 em comparação com 0,14 (p = 0,007)] e [0,65 em comparação com 0,36 (p = 0,004)], respectivamente. A IL-6 e a IL-10 demonstraram correlação positiva com a gravidade da doença (0,450; p = 0,001) e (0,410; p = 0,002), respectivamente. O TNF-α não mostrou relevância na gravidade da doença (0,100; p = 0,478). Com relação à avaliação nutricional, a IL-6 demonstrou correlação negativa com o desvio padrão de estatura para a idade (−0,493; p < 0,001) e o desvio padrão de espessura da prega cutânea do tríceps para a idade (−0,503; p < 0,001), respectivamente. A IL-10 demonstrou correlação negativa com o desvio padrão de estatura para a idade (−0,476; p < 0,001) e o desvio padrão de espessura da prega cutânea do tríceps para a idade (−0,388; p = 0,004), respectivamente. O TNF-α não mostrou relevância em ambos os parâmetros antropométricos [(−0,083; p = 0,555); (−0,161; p = 0,253)]. Conclusão: Assim, sugerimos que, em pacientes com cirrose secundária a atresia biliar, IL-6 pode ser usado como um possível biomarcador de suporte do estado nutricional deficiente e níveis aumentados de IL-10 podem ser usados como um possível biomarcador de suporte, em fase inicial, de deterioração do estado nutricional.

Seguimiento de pacientes con atresia biliar: cirugía tardía y desarrollo de lagunas biliares / Follow up for a cohort of patients with biliary atresia: late surgery and development of biliary cysts

Las dilataciones quísticas de las vías biliares, conocidas como lagunas biliares, se han descrito en el seguimiento de los pacientes sometidos a portoenterostomía o cirugía de Kasai por atresia de las vías biliares (AVB). Su aparición se ha asociado con el desarrollo de colangitis y consecuentemente a un peor pronóstico. OBJETIVO: Describir las características clínicas y pronóstico de pacientes con AVB, sometidos a cirugía de Kasai, con énfasis en aquellos que desarrollaron lagunas biliares. PACIENTES Y MÉTODO: Estudio retrospectivo de pacientes sometidos a portoenterostomía de Kasai por AVB durante los años 2008 a 2016. Se tabuló la información demográfica y variables asociadas a la portoenterostomía de Kasai, trasplante hepático, lagunas o quistes biliares y episodios de colangitis. Se crearon curvas de Kaplan Meier y comparación mediante el test de Log Rank para evaluar sobrevida global, libre de colangitis y con hígado nativo, considerando un valor p como significativo. RESULTADOS: Se analizó el seguimiento de 13 pacientes. El tiempo promedio de realización del Kasai fue a los 85 meses (rango 42-193, DS 40,3), seis pacientes (46%) fueron sometidos a cirugía de Kasai después de los 90 días de vida por derivación tardía. Cuatro (31%) desarrollaron lagunas biliares múltiples, todos presentaron episodios de colangitis. La sobrevida libre de colangitis fue significativamente menor para los portadores de lagunas biliares. Nueve pacientes (69%) recibieron un trasplante hepático, en promedio a los 16 meses de edad (rango 6-40, DS 12,1), en 3 de ellos la causa fue colangitis recurrente. No se encontraron diferencias significativas en la sobrevida con hígado nativo ni en sobrevida global entre portadores y no portadores de lagunas biliares. CONCLUSIONES: En esta cohorte, la incidencia de lagunas biliares luego de la portoenterostomía es similar a la descrita en la literatura. Los resultados concuerdan con la relación propuesta entre ellas y el desarrollo de colangitis. En los pacientes de nuestra serie, el diagnóstico y derivación de AVB fue realizado tardíamente, determinando un peor pronóstico.

Since the introduction of Kasai’s hepatic portoenterostomy, the prognosis of patients with biliary atresia has improved. The presence of intrahepatic biliary cysts or bile lakes has been reported in some patients after the intervention. Bile lakes have been related to cholangitis and a poor outcome. OBJECTIVE: To describe the clinical features and prognosis of patients with biliary atresia after Kasai portoenterostomy, with special emphasis in those who developed biliary cysts. PATIENTS AND METHOD: Data from a retrospective cohort of 13 patients with biliary atresia with a Kasai portoenterostomy from 2008 to 2016 was analyzed. Demographic variables associated to Kasai portoenterostomy, hepatic transplant, biliary cysts and colangitis episodes were tabulated. Kaplan Meir and Log Rank test were used to evaluate colangitis-free and native liver survival. RESULTS: The mean age at Kasai was 85 months (SD 40.3, 42-193 months), six patients (46%) had a Kasai operation after 90 days of life. Four patients (31%) developed multiple biliary cysts; all of them had at least one episode of cholangitis. Cholangitis-free survival was significantly lower for those who developed bile lakes. Nine patients (69%) underwent liver transplant, 3 of them because of recurrent cholangitis. There were no differences in global survival or native liver survival between patients with or without biliary cysts. CONCLUSIONS: The incidence of biliary cysts after Kasai portoenterostomy in this series is similar to the reported. The results are consistent with the relationship proposed between the development of biliary cysts and cholangitis. Our patients, some already derived for evaluation and liver transplantation, underwent Kasai operation at an advanced age, which determines a poor prognosis.

Environmental risk factors associated with biliary atresia in Rio Grande do Sul, Brazil

Biliary atresia (BA) seems to be a multifactorial disorder in which environmental factors interact with the patient's genetic constitution. This study aimed to analyze information concerning environmental risk factors associated with BA in southern Brazil. A case-control study with mothers of patients with BA and mothers of patients with cystic fibrosis (CF) was conducted. Inquiry included questions related to exposition to environmental risk factors during the periconceptional and gestational (second and third trimesters) periods. Mothers of BA patients had smoked during pregnancy more frequently in comparison with the mothers of CF patients, but no significant difference was found in a multivariate analysis. There was no between group difference in terms of seasonality, but the multivariate analysis showed a significant difference within the BA group between date of conception in winter compared to other seasons. In conclusion, smoking during pregnancy seemed to increase the risk of BA while date of conception in winter decreased it (AU)

Colestasis en pediatría / Cholestasis in Pediatrics

La colestasis indica siempre un proceso patológico que puede dejar secuelas como disfunción hepática crónica, necesidad de trasplante hepático o muerte (1). La colestasis es un proceso en el que existe disminución del flujo biliar, evidencia histológica de depósito de pigmentos biliares en los hepatocitos y conductos biliares, y aumento de la concentración sérica de los productos excretados en la bilis. La colestasis puede presentarse a cualquier edad y la causa es la alteración de la formación de bilis por el hepatocito o la obstrucción del flujo en la vía biliar intrahepática o extrahepática. Nos referimos a colestasis neonatal cuando se presenta en los primeros 3 meses de vida con elevación de niveles séricos de bilirrubina directa, colesterol y ácidos biliares (2). En nuestro medio la principal causa es la hepatitis neonatal idiopática, seguida de las causas infecciosas. Las causas obstructivas son las de peor pronóstico; dentro de estas la más común es la atresia de vías biliares, donde hay obliteración progresiva de la vía biliar extrahepática, daño del parénquima y vía biliar intrahepática, lo que causa cirrosis y muerte antes de los 3 años de vida (1-3). El pronóstico mejora con el manejo quirúrgico si este se realiza antes de los 45 a 60 días de vida (3). La forma de presentación más usual es en un recién nacido a término sano que entre las semanas 2 y 6 de vida presenta ictericia, hipocolia, hepatomegalia firme y esplenomegalia. El diagnóstico se apoya con la elevación de gamma glutamiltransferasa como principal marcador sérico, la ecografía de hígado con ayuno que tiene la mayor sensibilidad y especificidad, siendo el único método confirmatorio la laparotomía exploratoria con visión directa de la vía biliar mediante la realización intraoperatoria de colangiografía (4). En el manejo de todo paciente con colestasis, además de corregir la causa y tratar la colestasis, está el manejo nutricional con una dieta que ofrezca alto aporte de triglicéridos de cadena media y de vitaminas liposolubles (5).

Cholestasis always indicates a pathological process that can result in chronic liver dysfunction, the necessity of liver transplantation and even death. (1) Cholestasis is a process in which there is a decrease in biliary flow, histological evidence of deposition of bile pigments in hepatocytes and bile ducts, and an increase in the serum concentrations of products excreted in bile. Cholestasis can occur at any age. It is caused by alteration of the formation of bile by the hepatocytes or by obstruction of the flow in the intrahepatic or extrahepatic biliary tracts. Neonatal cholestasis occurs in the first (3) months of life with elevated serum levels of direct bilirubin, cholesterol and bile acids. (2) In our environment, the most frequent cause is idiopathic neonatal hepatitis, followed by infectious causes. Obstructive causes have the worst prognoses. Among them, the most common is biliary atresia in which progressive obliteration of the extra hepatic biliary tract, parenchymal damage and intrahepatic biliary tract cause cirrhosis and death before the patient reaches three years of age. (1-3) The prognosis improves with surgical management if it is performed within the first 45 to 60 days of life. (3) The most common presentation is a healthy full-term newborn who develops jaundice, hypocolony, firm hepatomegaly and splenomegaly between the 2nd and 6th weeks of life. The principal serum marker that supports diagnosis is elevation of gamma glutamyltransferase while ultrasound of the liver following fasting has the greatest sensitivity and specificity. The only method for confirming the diagnosis is exploratory laparotomy with direct vision of the bile duct by intraoperative cholangiography. (4) In addition to correcting the cause and treating cholestasis, nutritional management with an adequate diet with high levels of medium chain triglycerides and fat-soluble vitamins is important for management of all patients with cholestasis. (5)

Clinical and pathological challenges in the diagnosis of late-onset biliary atresia: four case studies

Biliary atresia (BA) is classically described at the neonatal age. However, rare cases of BA in older infants have also been reported. We report four cases of late-onset BA in infants older than 4 weeks (3 males, 1 female), and describe the diagnostic and management difficulties. One of the cases had a late-onset (29 weeks) presentation with a successful surgical procedure. We highlight the importance of this unusual differential diagnosis in infants with cholestatic syndrome, who may benefit from Kasai surgery, regardless of age.

Atresia biliar sindrómica en un paciente pediátrico: Reporte de caso / Case Report of Syndromic Biliary Atresia in a Pediatric Patient

La atresia de vías biliares es una colangiopatía obstructiva neonatal de etiología desconocida que produce una lesión del parénquima hepático y de la vía biliar intrahepática y extrahepática. Representa la causa más común de colestasis neonatal y trasplante hepático en la población pediátrica y se manifiesta como malformación aislada en la mayoría de los casos. Se presenta un caso de un paciente de 75 días de vida con atresia de vías biliares asociado a heterotaxia abdominal. El síndrome de atresia biliar y malformación esplénica ha sido descrito previamente como atresia de vías biliares asociado a malformaciones anatómicas del bazo, páncreas, alteraciones cardíacas y en menor frecuencia malformaciones genitourinarias. El pronóstico de los pacientes con atresia de vías biliares ha mejorado notoriamente con el reconocimiento temprano de los signos semiológicos y con la realización de la portoenterostomía (Kasai) en forma oportuna para lograr mejorar la sobrevida de los pacientes con atresia de vías biliares sindrómica.

Biliary atresia is an obstructive neonatal cholangiopathy of unknown etiology that produces damage to the parenchyma of the liver and to the intrahepatic and extrahepatic bile ducts. It is the most common cause of neonatal cholestasis and liver transplantation in the pediatric population. In most cases it manifests as an isolated malformation. This article presents the case of a 75 day old patient with biliary atresia associated with abdominal heterotaxy. Biliary atresia syndrome together with splenic malformation has been previously described, as have biliary atresia associated with anatomical malformations of the spleen, pancreas, and heart. It occurs with genitourinary malformations less frequently. The prognosis of patients with biliary atresia has significantly improved with early recognition of signs and symptoms and timely performance of hepatoportoenterostomy (Kasai portoenterostomy).

Colestasis neonatal: reporte de 21 casos en un hospital infantil de Cartagena, Colombia / Report of 21 Cases of Neonatal Cholestasis in a Children’s Hospital in Cartagena, Colombia

La colestasis es una alteración en el flujo biliar que se presenta por la disminución o el cese de excreción biliar. En la actualidad, son pocos los estudios en Colombia sobre esta patología. Se presentan 21 casos de colestasis neonatal en un hospital infantil de la ciudad de Cartagena (Colombia) entre 2010 y 2013, con el objetivo de caracterizar la etiología y clínica de la enfermedad. Se seleccionaron los pacientes entre 0 y 3 meses de edad con bilirrubina directa >2 mg/dL. En este estudio se encontró que según el género, el 52,4% fueron de sexo masculino y el 47,6%, de sexo femenino. La edad gestacional predominante fue a término en el 76,2% y sin antecedentes perinatales en el 57,1%. Los hallazgos clínicos se presentaron en los primeros 30 días de nacido en un 71% y 4 pacientes fueron remitidos a trasplante hepático. La etiología más frecuente fue de tipo infeccioso en 13 de los pacientes estudiados y 4 pacientes se relacionaron con atresias. La causa más frecuente de colestasis neonatal en este estudio resultó estar asociada con etiologías infecciosas. Sin embargo, las alteraciones obstructivas, como la atresia de vías biliares, siguen ocupando un renglón importante y requieren un estudio y manejo prioritario, dado su mejor pronóstico relacionado con la intervención temprana.

Cholestasis is an alteration in the flow of bile resulting from decreases or cessation of biliary excretion. To date, there have been only a few studies on this topic in Colombia. This article presents twenty-one cases of neonatal cholestasis from a Children’s Hospital in Cartagena, Colombia that occurred between 2010 and 2013. The aim of this study is to characterize the etiology and clinical characteristics of the disease. Patients between birth and 3 months old with direct bilirubin levels over 2 mg/dl were selected. By gender, 52.4% of the patients were male, and 47.6% were female. 76.2% of the patients were full term, and 57.1% had no perinatal antecedents. Clinical symptoms presented in the first 30 days after birth in 71% of the patients, and 4 patients were referred for liver transplantation. The most common etiology was infectious (13 patients), and 4 patients had atresia. The most common cause of neonatal cholestasis in this study was infection, but obstructive disorders such as biliary atresia still account for an important proportion of the patients. They require priority study and handling because early intervention results in better prognoses.

Padrões histopatológicos e deposição de colágenos durante a progressão da fibrose hepática como fatores prognósticos da atresia de vias biliares / Histopathological and collagens deposition patterns during hepatic fibrosis progression as prognostic factors in

Atresia de vias biliares (AVB) é uma hepatopatia colestática específica da criança, de etiologia desconhecida, com evolução para fibrose hepática precoce. AVB é a principal causa de cirrose na infância e principal indicação de transplante hepático pediátrico (Tx). Compreender os fatores envolvidos na progressão da fibrose é fundamental para estabelecer tratamentos efetivos nas hepatopatias crônicas. Identificar padrões histopatológicos associados ao prognóstico da AVB permitiria melhor planejamento dos centros de transplante e adequado aconselhamento familiar. OBJETIVO: Estabelecer padrões de marcadores histopatológicos e de imunofluorescência para colágenos em biópsias hepáticas iniciais e finais de pacientes com AVB submetidos a tratamento cirúrgico. Correlacionar esses marcadores com o prognóstico da doença, definido com base no tempo de evolução até realização do Tx. MÉTODO: Avaliação histológica de alterações biliares e fibrose hepática e histomorfometria da fibrose marcada por picrossírius e da deposição dos colágenos tipos I, III, IV e V marcados por imunofluorescência indireta (IF), em biópsias hepáticas iniciais e finais de 36 pacientes com AVB submetidos à hepatoportoenterostomia de Kasai (KPE) e ao Tx nos últimos 20 anos em nossa instituição. RESULTADOS: A mediana das idades de realização da KPE foi de 12,5 semanas (6-20) e do Tx foi de 27 meses (6-120). Reação ductular e malformação de placa ductal foram mais intensas nas biópsias iniciais (p < 0,05), enquanto fibrose hepática e ductopenia apresentaram padrão progressivo (p < 0,001), sem correlações com a idade de realização da KPE nem com o tempo de evolução até Tx. A morfometria da fibrose hepática marcada pelo picrossírius nas biópsias iniciais apresentou correlação positiva com a idade da KPE (p = 0,01), mas não com a idade do Tx (p = 0,24). A deposição perissinusoidal dos colágenos dos tipos III e V foi mais intensa nas biópsias iniciais (p < 0,01), enquanto os colágenos dos tipos I e IV...

Biliary atresia (BA) is a specific cholestatic liver disease of unknown etiology that affects children and progresses to early hepatic fibrosis. BA is the main indication of pediatric liver transplantation (LTx). Understanding the factors involved in the progress of fibrosis is essential to establish effective treatment to chronic liver disease. Histopathological markers in liver biopsies could be useful to predict progression to end stage disease and to make it possible to improve planning in transplantation centers and parental orientation. OBJECTIVE: To establish histopathological or immunohistochemical markers in initial or final liver biopsies of BA patients and correlate those markers with prognosis, as defined by progression time lapse until LTx. METHOD: Histological analysis of multiple parameters of biliary alterations and morphometrical assessment of liver fibrosis were performed, besides indirect immunofluorescence assays (IF) for type I, III, IV and V collagens in initial and final liver biopsies of 36 patients with BA submitted to Kasai hepatoportoenterostomy (KPE) and LTx in the last 20 years in a single center. RESULTS: The median of the ages at KPE was 12.5 weeks (6-20) and at LTx was 27 months (6-120). Ductular reaction and ductal plate malformation were more severe in the initial biopsies (p < 0.05), while ductopenia and liver fibrosis were more severe in final biopsies (p < 0.001), though without correlation with age at KPE nor with progression time lapse until LTx. Morphometrical assessment of liver fibrosis marked by picrosirius red in initial biopsies demonstrated positive correlation with age at KPE (p = 0.01) but not with age at LTx (p = 0.24). The perisinusoidal deposition of type III and V collagens was more extended in the initial biopsies (p < 0.01), while type I and IV collagens deposition indicated progression (p < 0.01). Patients with large amounts of perisinusoidal type I collagen in the initial biopsies had worse...