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.

Cyclooxygenase-2 Inhibitor Reduces Hepatic Stiffness in Pediatric Chronic Liver Disease Patients Following Kasai Portoenterostomy

PURPOSE: The purpose of this study was to define the role of cyclooxygenase-2 inhibitors (COX-2i) in reducing hepatic fibrosis in pediatric patients with chronic liver disease. MATERIALS AND METHODS: From September 2009 to September 2010, patients over 2 years old who visited our outpatient clinic for follow-up to manage their chronic liver disease after Kasai portoenterostomy for biliary atresia, were included in this study. Volunteers were assigned to the study or control groups, according to their preference. A COX-2i was given to only the study group after obtaining consent. The degree of hepatic fibrosis (liver stiffness score, LSS) was prospectively measured using FibroScan, and liver function was examined using serum analysis before and after treatment. After 1 year, changes in LSSs and liver function were compared between the two groups. RESULTS: Twenty-five patients (18 females and 7 males) were enrolled in the study group. The control group included 44 patients (26 females and 18 males). After 1 year, the least square mean values for the LSSs were significantly decreased by 3.91±0.98 kPa (p=0.004) only in the study group. Serum total bilirubin did not decrease significantly in either group. CONCLUSION: COX-2i treatment improved the LSS in patients with chronic liver disease after Kasai portoenterostomy for biliary atresia.

Atresia biliar: una enfermedad grave / Biliary atresia: a severe illness

La atresia biliar es una grave enfermedad que se manifiesta en los recién nacidos, y se desconoce su causa. La inflamación y destrucción progresiva de los conductos biliares conducen a la aparición de ictericia, coluria y acolia entre la segunda y sexta semana de vida. Como existen múltiples causas de colestasis neonatal en esta etapa de la vida, es necesario realizar un diagnóstico y derivación precoz para ofrecer un tratamiento quirúrgico, con el fin de restablecer el flujo biliar. Alrededor del 80% de los pacientes normalizan la bilirrubina luego de la portoenterostomía (operación de Kasai), realizada antes de los 45 días de vida. Si la operación fracasa, el trasplante hepático surge como única alternativa. La atresia biliar debe diagnosticarse durante el primer mes de vida y ser considerada una urgencia quirúrgica.

Biliary atresia is a serious disease of unknown cause, affecting newborns. An inflammation and progressive destruction of the bile ducts lead to jaundice, dark urines, and acholia, between the second and sixth weeks of life. Neonatal cholestasis could be due to several different diseases, thus a diagnosis of biliary atresia and early derivation for surgical treatment are necessary to allow a restoration of the bile flow. Eighty percent of the children normalize serum bilirubin after the portoenterostomy (Kasai operation), if they are operated before their 45 days of life. When Kasai operation fails, a liver transplantation is the only possibility. Biliary atresia must be diagnosed before the first month of life and must be considered as a surgical emergency.

Hemorragia intracraneal como forma de presentación de atresia biliar: presentación de dos casos / Intracranial hemorrhage as initial presentation of biliary atresia: two cases report

La atresia biliar en lactantes se presenta habitualmente con la tríada ictericia, acolia y coluria, y ocasionalmente con sangrado intracraneal, nasal o gastrointestinal. Presentamos dos niñas, de cuatro y dos meses, que fueron asistidas por presentar convulsiones, cefalohematoma y sopor. En la tomografía computada cerebral se halló hemorragia subdural en una paciente e intraventricular y parenquimatosa en la otra. Al ingreso, presentaban antecedentes, signos clínicos y de laboratorio de colestasis, sin diagnóstico etiológico. La niña con hematoma subdural requirió drenaje quirúrgico. La paciente con sangrado intraventricular y parenquimatoso no requirió cirugía y se le administró vitamina K. Se diagnosticó atresia de vías biliares mediante centellograma con HIDA y colangiografía intraoperatoria previa al procedimiento de Kasai (portoenteroanastomosis). Ambas niñas presentaron buena evolución neurológica a los seis meses. Requirieron trasplante de hígado alrededor del año de vida. La atresia biliar se debe considerar en el diagnóstico de lactantes pequeños que presentan sangrado agudo y colestasis.

Biliary atresia in infants occasionally presents as intracranial, nasal or gastrointestinal bleeding, instead of the classical triad of jaundice, acholia and choluria. We present two female infants aged four and two months, who were hospitalized with convulsive episode, cephalohematoma and drowsiness. Computed tomography fndings were subdural hemorrhage in one patient and intraventricular and parenchymal bleeding in the other one. At admission they have history, clinical and laboratory signs of cholestasis of unknown etiology. The patient with subdural hemorrhage required surgical drainage. The other girl with intraventricular and parenchymal bleeding received vitamin K and no surgery. Biliary atresia was diagnosed and treated in both girls. At six months both had an adequate neurological outcome and required liver transplantation at one year old. Biliary atresia should be considered in all infants with sudden acute bleeding and cholestasis.

Factors influencing outcome after hepatic portoenterostomy for biliary atresia: a logistic regression analysis.

BACKGROUND/OBJECTIVE: The association of many factors with the outcome in Biliary atresia (BA) after hepatic portoenterostomy has drawn the attention of many pediatric hepatologists and hepatobiliary surgeons. Understanding these factors will become an important subject in prediction of the postoperative status and in indicating further proper management. MATERIAL AND METHOD: During the last 9 years, 159 BA babies were treated by hepatic portoenterostomy. The authors reviewed the following factors and how they related to outcome: age at operation, total bilirubin (TB) level, type of BA, postoperative bile drainage, hepatic histological features at operation, preoperative and postoperative cholangitis. A multiple logistic regression analysis was used to indicate the factors which significantly influenced the outcome. RESULTS: Of the 159 BA babies, clearing of jaundice confirmed by the color of stool and postoperative serum bilirubin level less than 2 mg % was observed in 54 patients (Group A). Bile drainage with mild jaundice (TB 2-5 mg %) was detected in 65 patients (Group B). The operation failed to create bile flow clinically and biochemically in 40 patients (Group C). Some patients in the last group died during follow-up due to hepatic disease. The multiple logistic regression analysis revealed that the age at operation (> 8 weeks of age), and the presence of portal and parenchymal inflammation at operation significantly related to the failure of portoenterostomy which was followed by portal hypertension with or without esophageal varices. The presence of cholangitis was also significantly related to a poor outcome. CONCLUSION: The age at operation, portal and parenchymal inflammation and the presence of cholangitis are significant factors which relate to the poor prognosis of BA. Recognition of these will lead to proper long-term management.

Essential fatty acid status in infants and children with chronic liver disease

The relationship between essential fatty acid [EFA] status and degree of hyperbilirubinaemia and oxidant stress in infants and children with chronic liver diseases was evaluated. Thirty patients with chronic cholestasis and 30 with liver cirrhosis were examined; 30 healthy subjects served as controls. Patient groups had significant decreases in EFAs and significant elevation of total bilirubin. Levels of thiobarbituric acid reactive substances were significantly raised and were significantly inversely correlated to decreased EFA levels. There were also significant decreases in retinol, alpha-tocopherol and alpha-tocopherol/total lipids ratio, which had significant positive correlations with decreased EFA levels. Infants and children with chronic liver diseases have a high risk of EFA deficiency correlated with progressive elevation of serum bilirubin and progressive deterioration of oxidant status

An unusual case of biliary atresia.

Intrahepatic biliary cysts are rarely seen in the patients with biliary atresia. We describe a ten-month-old child with biliary atresia in whom the abdominal imaging studies (ultrasonography, computed tomographic scan and magnetic resonance cholangiopancreatography) revealed multiple intrahepatic biliary cysts ('bile lakes'). The child also had intrapulmonary shunting of blood due to pulmonary arteriovenous fistulae, which were demonstrated on contrast-enhanced echocardiography. Both these findings, 'bile lakes' and pulmonary arteriovenous fistulae occur rarely in biliary atresia.

Non-syndromic paucity of interlobular bile ducts.

A 3 1/2-month-old male infant presented with cholestatic jaundice. Peroperative cholangiogram showed a gall bladder and small but patent extrahepatic bile ducts. Liver histology showed paucity of interlobular bile ducts. The child is being treated medically for his symptoms.

Restrictive Cardiomyopathy in a Patient with Extrahepatic Biliary Atresia

The most commonly associated anomalies in patients with extrahepatic biliary atresia are cardiovascular, digestive and splenic defects. Of the cardiovascular anomalies, there are very few reports of biliary atresia with cardiomyopathy. We report the first case of a child with extrahepatic biliary atresia and restrictive cardiomyopathy. The patient was a 13-month-old boy diagnosed with extrahepatic biliary atresia at the age of 2 months, when he underwent laparotomy for definite diagnosis.Hepatic portoenterostomy was performed after confirmative cholangiogram. Recently, he developed severe cough and dyspnea, and his respiratory symptoms worsened. Chest radiograph showed cardiomegaly. Two- dimensional echocardiography showed marked biatrial enlargement. On M- mode echocardiogram, a slight increase in left ventricular dimension was seen in early diastole with a relatively good left ventricular function. Mitral inflow Doppler tracing showed an increased E-velocity (1.1 m/sec) with decreased deceleration time (75 m/sec), and increased E/A ratio (0.33). He was diagnosed as having restrictive cardiomyopathy with characteristic echocardiographic features.

Crecimiento físico en niños sometidos a trasplante hepático / Physical growth in children undergoing liver transplant

El trasplante hepático (T. H.) constituye una opción válida en diversas enfermedades hepáticas de la infancia que no pose en una alternativa. El objetivo del trabajo es utilizar el crecimiento como un indicador para evaluar el exito de un plan T.H. en los niños sobrevivientes. De un total de 64 trasplantes realizados en 62 niños, desde noviembre de 1992 a enero de 1996, se estudiaron 31 niños seguidos por un período de 0.50 a 3.55 años, en los que se efectuaron mediciones antroprométricas seriadas, y evaluación de la maduración esquelética. Los resultados muestran que el crecimiento post- T-H., es diferente según distintos grupos. Los pacientes con atresia de vias biliares (A. V. B) y cirrosis autoinmune (CA) presentan un deficit de estatura similar al inicio del seguimiento (-1.14 y -1.39 DS) pero difieren en su evolución post T.H.: el grupo de AVB presenta crecimiento recuperatorio (CR) de 1.18 más menos 0.24 (P <0.005); los niños con (CA) 3n en cambio no mostraron CR y crecieron a una velocidad normal. Los pacientes con fallo hepático fulminante no presentan al momento del T.H deterioro alguno de su estatura y tienen un crecimiento post T.H normal. El cuarto grupo grupo (miscelánea) tiene un deficit inicial severo de talla, sin C.R. ulterior. La edad ósea pre T.H. estuvo retrasada con respecto a la edad cronológica -0.67 en grupo de pacientes crónicos, siendo la velocidad de edad ósea post T.H. normal. El crecimiento físico resulta un adeacudo indicador para evaluar la evolución a largo plazo de los niños con T.H. exitoso.

Icterícia: atresia de vias biliares / Jaundice: biliary tract atresia

O presente trabalho tem por objetivo alertar para a importância do diangóstico e tratamento precoce da hiperbilirrubinemia direta, por atresia de vias biliares, devido a sua grande complicaçäo que é a cirrose hepática e conseqüente morte do lactente. O médico dispöe de pouco tempo entre o diagnóstico e o tratamento quando possível, sendo que após 2 a 3 meses, terá danos irreversíveis ao lactente. Quando houver quadro icterico, com acolia fecal, colúria, e predomínio da bilirrubina direta, sempre ter na hipótese diagnóstica a atresia de vias biliares. Por ser uma patologia de baixa incidência, muitas vezes poderá passar desapercebido,levando o lactente a condenaçäo