Evaluation of the presence of hereditary and acquired thrombophilias in Brazilian children and adolescents with diagnoses of portal vein thrombosis.

OBJECTIVE: The aim of this study was to describe the prevalence of main hereditary thrombophilias, Janus kinase 2 (JAK2) V617F mutation, antiphospholipid antibody syndrome (APS), and hyperhomocysteinemia in Brazilian children and adolescents diagnosed with portal vein thrombosis (PVT) without associated hepatic disease. METHODS: A cross-sectional study was carried out with 32 children with PVT in accompaniment at Hospital das Clínicas of the Universidade Federal de Minas Gerais from January 1990 to July 2011. Laboratory evaluation of thrombophilias was performed from September 2010 to July 2011. RESULTS: Thirty-two patients were evaluated; 59% were boys. Median age at diagnosis was 2.4 years. Mean time of patients' accompaniment was between 4.7 and 5.2 years. The presence of hereditary and acquired thrombophilias occurred in 34.4% of patients, and 9 of them also showed other risk factors in the previous history evaluation. Risk factors were absent in the previous history of 18 patients (56.3%). Two patients showed persistent high titres of anticardiolipin antibodies. Hyperhomocysteinemia was not observed. One patient was heterozygous for factor V Leiden and prothrombin G20210A mutation (3.1%). Eleven patients (34.4%) showed heterozygous methylenetetrahydrofolate reductase (MTHFR) C677T, and no patient had the JAK2V617F mutation. CONCLUSIONS: Even after investigation of main hereditary and acquired thrombophilia, PVT remains without apparent cause in most patients. Nevertheless, association of local and systemic risk factors seems to be important also in the pediatric age group. Therefore, despite the low prevalence, a complete investigation, which includes both hereditary and acquired thrombophilias, may be necessary.

Effect of treatment of hepatic histopathology in children and adolescents with autoimmune hepatitis.

OBJECTIVE: To evaluate the effects of treatment on liver histopathology of children and adolescents diagnosed with autoimmune hepatitis. PATIENTS AND METHODS: Histopathological evaluation of liver biopsies performed at diagnosis or early during treatment, compared with biopsies after immunosuppressive treatment of 20 children and adolescents diagnosed with autoimmune hepatitis who presented clinical and biochemical remission for at least 24 months. Liver histopathology was assessed by 2 pathologists. Agreement between their interpretations was analyzed with kappa statistics. RESULTS: The age at diagnosis of the 20 patients varied from 1.7 years to 11.6 years (median = 6.6 years); 18 were females. The mean duration of clinical and biochemical remission, up to performance of liver biopsy, was 4.1 years. The mean interval between the initial and posttreatment biopsies was 4.6 years (range 2-9.7 years). Assessing the necroinflammatory activity, a mean reduction by 6.3 (observer 1) and 7.3 (observer 2) in the grading score was observed (P = 0.00000). When staging was assessed, a mean reduction by 1.8 (observers 1 and 2) in the score was observed after treatment (P = 0.00008), and there was no progression toward cirrhosis. No regression of cirrhosis was observed. CONCLUSIONS: On histopathological evaluation, the immunosuppressive treatment improved the fibrosis scores, with an arrest in its progression and no development into cirrhosis. Fibrosis control is mainly associated with regression of necroinflammatory activity, which is the main treatment component in autoimmune hepatitis.

Clinical and laboratory predictors of esophageal varices in children and adolescents with portal hypertension syndrome.

OBJECTIVES: To determine the clinical and laboratory parameters that may predict the presence of esophageal varices in children and adolescents with portal hypertension. PATIENTS AND METHODS: Overall, 111 patients with portal hypertension and no previous history of digestive bleeding underwent esophagogastroduodenoscopy for detection of esophageal varices. A univariate analysis initially was carried out, followed by a logistic regression analysis to identify the independent variables associated with the presence of esophageal varices. Sensitivity and specificity rates, positive predictive value, negative predictive value, and the accuracy of the predictive variables identified among cirrhotic patients were calculated with the esophagogastroduodenoscopy as the reference test. RESULTS: Sixty percent of patients had esophageal varices on the first esophagogastroduodenoscopy. Patients with portal vein thrombosis and congenital hepatic fibrosis were 6.15-fold more likely to have esophageal varices than cirrhotic patients. When we analyzed 85 cirrhotic patients alone, splenomegaly and hypoalbuminemia remained significant indicators of esophageal varices. Only spleen enlargement showed appropriate sensitivity and negative predictive value (97.7% and 91.7%, respectively) to be used as a screening test for esophageal varices among cirrhotic patients. CONCLUSIONS: In reference services and research protocols, endoscopic screening should be performed in all patients with portal vein thrombosis and congenital hepatic fibrosis. Among cirrhotic patients, the indication should be conditioned to clinical evidence of splenomegaly or hypoalbuminemia. For clinicians, the recommendation is to emphasize the orientations given to guardians of patients with portal vein thrombosis and congenital hepatic fibrosis as to the risk of digestive bleeding. Cirrhotic patients with hypoalbuminemia and splenomegaly should receive the same orientations.

[Risk factors for cystic fibrosis related liver disease]. / Fatores de risco da hepatopatia da fibrose cística.

OBJECTIVE: To identify the risk factors for cystic fibrosis related liver disease. METHODS: Ten patients out of a total of 106 patients regularly followed-up during 1999 met the clinical, biochemical and/or ultrasound criteria for liver disease (9.4%). Using information from the admissions records at the service, we collected data on demography, genotype, age and manifestations at diagnosis of cystic fibrosis, nutritional status and laboratory findings. Variables associated with liver disease were initially identified by the Kaplan-Meier method. Those factors that were significant in the univariate analysis were included in the multivariate analysis by means of a Cox regression model. RESULTS: Under univariate analysis the following factors were associated with liver disease: male sex, age at diagnosis of cystic fibrosis, pancreatic insufficiency, z score for weight at admission, Shwachman score and biochemistry at admission. After adjustment by Cox model, two variables were independently associated with liver disease: Shwachman score (p = 0.0057) and age at diagnosis of cystic fibrosis (p = 0.014). CONCLUSIONS: The risk of developing liver disease is higher among patients diagnosed at an early age and those with worse clinical status as assessed by the Shwachman score, indicating that liver involvement might be part of a more severe form of the condition. These patients merit greater attention in terms of screening for liver disease and should be given treatment with ursodeoxycholic acid earlier in the event of abnormal findings.

[Type 1 autoimmune hepatitis in children and adolescents: assessment of immunosuppressive treatment withdrawal]. / Hepatite auto-imune tipo 1 em crianças e adolescentes: avaliação da suspensão do tratamento imunossupressor.

OBJECTIVE: To assess treatment withdrawal in children and adolescents with autoimmune hepatitis, with clinical and laboratory remission for a minimum period of 24 months, determining the relapse rate after treatment withdrawal. METHODS: This is a descriptive, retrospective and partially prospective study of 21 children and adolescents with type 1 autoimmune hepatitis treated at the Outpatient Division of Pediatric Hepatology, Teaching Hospital of Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil, between January 1986 and December 2001. RESULTS: We assessed 54 patients and selected 21, of whom 19 were female subjects (90.5%), aged between 5.7 and 17.6 years (median = 13.8 years), with a mean follow-up of 5.1+/-2.4 years (median = 4.4 years) and an average clinical and laboratory remission of 4.1+/-1.5 years (median = 4.1 years). Out of the 21 patients studied, 10 (47.6%) manifested some inflammatory activity that prevented the discontinuation of treatment, which was withdrawn in 11 patients (52.4%). Out of these, six patients (54.5%) presented reactivation of the disease and five maintained clinical and laboratory remission with a mean follow-up of 4+/-1 years (median = 3.9 years). The time interval between discontinuation of treatment and reactivation of the disease ranged from 29 days to 40.3 months (median = 2.2 months). CONCLUSIONS: We observed a high relapse rate (54.5%) in this group of patients with autoimmune hepatitis, which was more frequent within the first 12 months after treatment withdrawal, in addition to a high number of patients that presented some degree of inflammatory activity despite the long period of clinical and laboratory remission.

Biliary atresia: evaluation on two distinct periods at a reference pediatric service.

CONTEXT: Biliary atresia is a progressive, idiopathic, fibro-obliterative disease of the extrahepatic biliary tree that presents with biliary obstruction exclusively in the neonatal period. OBJECTIVES: To assess the differences regarding age at referral, age at surgery, duration of propaedeutics and waiting time for surgery between two groups of infants in different periods. METHODS: Retrospective study of infants diagnosed with biliary atresia on two periods: 1983-1993 and 1998-2011. RESULTS: Biliary atresia was diagnosed in 129 infants, being 48 in casuistic I and 81 in casuistic II. The median age at admission was 94 and 60 days, respectively (P = 0.0001). On evaluating patients who had undergone portoenterostomy before 120 days of age, no difference was observed regarding the duration of propaedeutics or waiting time for surgery (P = 0.15), but difference was found when comparing the age at surgery (P = 0.002). Among those infants with no biliary flow and without liver transplantation or death after 18 post-operative months, the estimated probability of survival was 44.6% and 38.7% in casuistics I and II, respectively. In casuistic I, all infants who showed biliary flow were alive during the observation period and, in casuistic II, 80.3% were alive after 7 years of follow-up. CONCLUSIONS: Even though patients were admitted and treated earlier, it is clear that surgery could be done sooner. Delay in referral and timely propaedeutics were the main contributors.

Portal vein thrombosis in children and adolescents: 20 years experience of a pediatric hepatology reference center.

CONTEXT: Portal vein thrombosis refers to a total or partial obstruction of the blood flow in this vein due to a thrombus formation. It is an important cause of portal hypertension in the pediatric age group with high morbidity rates due to its main complication - the upper gastrointestinal bleeding. OBJECTIVE: To describe a group of patients with portal vein thrombosis without associated hepatic disease of the Pediatric Hepatology Clinic of the Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil with emphasis on diagnosis, presentation form and clinical complications, and the treatment of portal hypertension. METHODS: This is a descriptive study of a series of children and adolescents cases assisted from January 1990 to December 2010. The portal vein thrombosis diagnosis was established by ultrasound. RESULTS: Of the 55 studied patients, 30 (54.5%) were male. In 29 patients (52.7%), none of the risk factors for portal vein thrombosis was observed. The predominant form of presentation was the upper gastrointestinal bleeding (52.7%). In 20 patients (36.4%), the initial manifestation was splenomegaly. During the whole following period of the study, 39 patients (70.9%) showed at least one episode of upper gastrointestinal bleeding. The mean age of patients in the first episode was 4.6 ± 3.4 years old. The endoscopic procedure carried out in the urgency or electively for search of esophageal varices showed its presence in 84.9% of the evaluated patients. The prophylactic endoscopic treatment was performed with endoscopic band ligation of varices in 31.3% of patients. Only one died due to refractory bleeding. CONCLUSIONS: The portal vein thrombosis is one of the most important causes of upper gastrointestinal bleeding in children. In all non febrile children with splenomegaly and/or hematemesis and without hepatomegaly and with normal hepatic function tests, it should be suspect of portal vein thrombosis. Thus, an appropriate diagnostic and treatment approach is desirable in an attempt to reduce morbidity and mortality.

BILIARY ATRESIA: evaluation on two distinct periods at a reference pediatric service / Atresia biliar: avaliação em dois períodos distintos em um serviço de referência

Context Biliary atresia is a progressive, idiopathic, fibro-obliterative disease of the extrahepatic biliary tree that pre­sents with biliary obstruction exclusively in the neonatal period. Objectives To assess the differences regarding age at referral, age at surgery, duration of propaedeutics and waiting time for surgery between two groups of infants in different periods. Methods Retrospective study of infants diagnosed with biliary atresia on two periods: 1983-1993 and 1998-2011. Results Biliary atresia was diagnosed in 129 infants, being 48 in casuistic I and 81 in casuistic II. The median age at admission was 94 and 60 days, respectively (P = 0.0001). On evaluating patients who had undergone portoenterostomy before 120 days of age, no difference was observed regarding the duration of propaedeutics or waiting time for surgery (P = 0.15), but difference was found when comparing the age at surgery (P = 0.002). Among those infants with no biliary flow and without liver transplantation or death after 18 post-operative months, the estimated probability of survival was 44.6% and 38.7% in casuistics I and II, respectively. In casuistic I, all infants who showed biliary flow were alive during the observation period and, in casuistic II, 80.3% were alive after 7 years of follow-up. Conclusions Even though patients were admitted and treated earlier, it is clear that surgery could be done sooner. Delay in referral and timely propaedeutics were the main contributors. .

Contexto A atresia biliar é uma doença progressiva, idiopática, fibro obliterativa, da vias bilares extra hepáticas que se apresenta com obstrução biliar exclusivamente no periodo neonatal. Objetivos Caracterizar duas épocas distintas visando avaliar se ocorreram alterações quanto a idade de encaminhamento das crianças, idade cirúrgica, duração do tempo entre internação e realização da cirurgia de Kasai, resultados cirúrgicos quanto a presença de fluxo biliar e sobrevida entre dois períodos. Métodos Estudo retrospectivo de crianças com diagnóstico de atresia biliar em dois períodos: 1983-1993 e 1998-2011. Resultados Foram admitidas 129 crianças com diagnóstico de AB, 48 (casuística I) e 81 (casuística II), com idade de admissão mediana de 94 e 60 dias, nas casuísticas I e II, respectivamente (P = 0,0001). Na avaliação dos pacientes submetidos à portoenterostomia com idade até 120 dias de vida, não houve diferença em relação ao tempo entre internação e realização da cirurgia de Kasai (P = 0,15), mas ocorreu ao comparar a idade à cirurgia entre os dois períodos (P = 0,002). A probabilidade estimada de sobrevida dos pacientes sem fluxo biliar livre de transplante ou óbito em 18 meses foi de 44,6%, 38,7% nas casuísticas I e II, respectivamente. Com fluxo biliar, todos estavam vivos ao longo do seguimento da casuística I e 80,3% em sete anos na casuística II. Conclusões Apesar dos pacientes chegarem mais cedo e serem submetidos à portoenterostomia, ainda se opera tarde. Encaminhamento tardio e a propedêutica prolongada são os principais contribuintes. Quanto maior a idade cirúrgica, menor a probabilidade de se obter fluxo biliar e consequentemente menor sobrevida. .

Alerta amarelo: icterícia após duas semanas de vida é uma urgência pediátrica / Yellow alert: icterus after two weeks of life is equal of medical evaluation

A colestase neonatal manifesta-se clinicamente com icterícia, colúria, hipocolia ou acolia fecal. Reveste-se de grande importância, uma vez que requer propedêutica urgente e precisa, com o propósito de definir o diagnóstico e tratamento. Diante de todo recém-nascido cuja icterícia persista além dos 14 dias de vida, impõe-se a dosagem das bilirrubinas (total e fração) e a observação da coloração das fezes e urina. Uma vez confirmada a colestase, é necessário o encaminhamento urgente para umcentro de referência. Para investigação da causa da colestase, o uso de protocolo sistemático é útil para agilizar o diagnóstico. Atresia biliar, uma das principais causas de icterícia colestática, necessita de correção cirúrgica antes dos 60 dias de vida. Tal procedimento mostra-se bem-sucedido em 70 a 80% dos pacientes operados antes dessa idade. O encaminhamento tardio dos pacientes com suspeita de AB constitui um dos principais fatores para o fracasso da correção cirúrgica. Por isso, a divulgação da importância da análise da cor das fezes e da dosagem de bilirrubinas, a partir de campanhas como alerta amarelo, é necessária e deve atingir não apenas os pais, mas também os profissionais da saúde...

Neonatal cholestasis manifests clinically with jaundice, dark urine, fecal acholia or hipocholia. It is of great importance, since it requires urgent and precise propaedeutics to define diagnosis and treatment. Before every newborn whose jaundice persists beyond 14 days of life, it is necessary the dosage of bilirubin (total and fraction) and the color observation of feces and urine. Once confirmed cholestasis, it is required urgent transfer to a referral center. To investigate the cause of cholestasis, the use of systematic protocol is useful to accelerate the diagnosis. Biliary Atresia (BA), a major cause of cholestatic jaundice, requires surgical correction before 60 days of life. This procedure is successful in 70-80% of patients operated before this age.The late referral of patients with suspected BA is one of the main factors for the failure of surgical correction. Therefore,disclosure of the importance of analyzing the color of feces and the determination of bilirubin through campaigns such as yellow alert is required and must reach not only parents, but also health professionals...

Pediatric liver transplantation: 10 years of experience at a single center in Brazil.

OBJECTIVES: To evaluate the first 10 years' experience of the liver transplantation department at the Alfa Institute, Hospital das Clínicas da Universidade Federal de Minas Gerais, Brazil. METHODS: A descriptive study, based on a retrospective analysis of 84 children and adolescents enrolled on a liver transplantation waiting list, from March 1995 to January 2006, based on the following variables: age, etiology of underlying liver disease, Child-Pugh, Malatack, model for end-stage liver disease (MELD) and pediatric end-stage liver disease (PELD) scores, time on waiting list, complications and survival after the procedure. RESULTS: Forty children had 42 liver transplants. Twenty six died while on the waiting list. Biliary atresia was the most frequent indication for transplant. The median age was 6.6 years (ranging from 1.9 to 16.8 years). Post liver transplant mortality was 32.5% (13 of 40 children). The median time on the liver transplant waiting list was 291 days. Complications related to the graft occurred in 24 of 42 transplants (57.1%), including vascular complications (30.8%), with thrombosis of the hepatic artery being the most frequent (16.6%); acute rejection occurred in 16.6%. CONCLUSIONS: The overall results are similar to what can be found in the literature with relation to indications and post-transplant survival. However, there were elevated rates of complications unrelated to the graft and of complications involving the hepatic artery.

Portal vein thrombosis in children and adolescents: 20 years experience of a pediatric hepatology reference center / Trombose de veia porta em crianças e adolescentes: experiência de 20 anos de um serviço de referência em hepatologia pediátrica

CONTEXT: Portal vein thrombosis refers to a total or partial obstruction of the blood flow in this vein due to a thrombus formation. It is an important cause of portal hypertension in the pediatric age group with high morbidity rates due to its main complication - the upper gastrointestinal bleeding. OBJECTIVE: To describe a group of patients with portal vein thrombosis without associated hepatic disease of the Pediatric Hepatology Clinic of the Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil with emphasis on diagnosis, presentation form and clinical complications, and the treatment of portal hypertension. METHODS: This is a descriptive study of a series of children and adolescents cases assisted from January 1990 to December 2010. The portal vein thrombosis diagnosis was established by ultrasound. RESULTS: Of the 55 studied patients, 30 (54.5%) were male. In 29 patients (52.7%), none of the risk factors for portal vein thrombosis was observed. The predominant form of presentation was the upper gastrointestinal bleeding (52.7%). In 20 patients (36.4%), the initial manifestation was splenomegaly. During the whole following period of the study, 39 patients (70.9%) showed at least one episode of upper gastrointestinal bleeding. The mean age of patients in the first episode was 4.6 ± 3.4 years old. The endoscopic procedure carried out in the urgency or electively for search of esophageal varices showed its presence in 84.9% of the evaluated patients. The prophylactic endoscopic treatment was performed with endoscopic band ligation of varices in 31.3% of patients. Only one died due to refractory bleeding. CONCLUSIONS: The portal vein thrombosis is one of the most important causes of upper gastrointestinal bleeding in children. In all non febrile children with splenomegaly and/or hematemesis and without hepatomegaly and with normal hepatic function tests, it should be suspect of portal vein thrombosis. Thus, an appropriate diagnostic and treatment approach is desirable in an attempt to reduce morbidity and mortality.

CONTEXTO: Trombose da veia porta refere-se a uma obstrução total ou parcial do fluxo de sangue nesta veia devido à formação de um trombo. É uma causa importante da hipertensão porta na faixa etária pediátrica, com taxas elevadas de morbidade devido a sua principal complicação - a hemorragia digestiva alta. OBJETIVO: Descrever o grupo de crianças e adolescentes com trombose de veia porta sem doença hepática associada do Ambulatório de Hepatologia Pediátrica do Hospital das Clínicas da UFMG, Belo Horizonte, MG, Brasil, com ênfase no diagnóstico, forma de apresentação, complicações clínicas e na abordagem da hipertensão porta. MÉTODOS: Trata-se de estudo descritivo de uma série de casos de crianças e adolescentes atendidos de janeiro de 1990 a dezembro de 2010. O diagnóstico de trombose de veia porta foi estabelecido por ultrassonografia. RESULTADOS: Dos 55 pacientes analisados, 30 (54,5%) eram do gênero masculino. Em 29 pacientes (52,7%) não foi identificado nenhum fator de risco para trombose de veia porta. A forma de apresentação predominante foi hemorragia digestiva alta (52,7%). Em 20 pacientes (36,4%), a manifestação inicial foi esplenomegalia. Durante todo o período de seguimento, 39 pacientes (70,9%) apresentaram, pelo menos, um episódio de hemorragia digestiva alta. A média de idade dos pacientes neste primeiro episódio foi de 4,6 ± 3,4 anos. O exame endoscópico, seja realizado na urgência ou eletivamente para pesquisa de varizes esofágicas, mostrou sua presença em 84,9% dos pacientes avaliados. O tratamento endoscópico profilático foi realizado com ligadura elástica de varizes em 31,3% dos pacientes. Apenas um evoluiu para óbito devido a sangramento refratário. CONCLUSÕES: A trombose de veia porta é uma das causas mais importantes de hemorragia digestiva alta em crianças. Deve-se suspeitar de trombose de veia porta em toda criança com esplenomegalia afebril e/ou hematêmese, sem hepatomegalia e com testes de função hepática normais. Desta forma, uma abordagem diagnóstica e terapêutica adequada é desejável na tentativa de reduzir a morbimortalidade.

[Risk factors for cystic fibrosis related liver disease] / Fatores de risco da hepatopatia da fibrose cística.

OBJECTIVE: To identify the risk factors for cystic fibrosis related liver disease. METHODS: Ten patients out of a total of 106 patients regularly followed-up during 1999 met the clinical, biochemical and/or ultrasound criteria for liver disease (9.4%). Using information from the admissions records at the service, we collected data on demography, genotype, age and manifestations at diagnosis of cystic fibrosis, nutritional status and laboratory findings. Variables associated with liver disease were initially identified by the Kaplan-Meier method. Those factors that were significant in the univariate analysis were included in the multivariate analysis by means of a Cox regression model. RESULTS: Under univariate analysis the following factors were associated with liver disease: male sex, age at diagnosis of cystic fibrosis, pancreatic insufficiency, z score for weight at admission, Shwachman score and biochemistry at admission. After adjustment by Cox model, two variables were independently associated with liver disease: Shwachman score (p = 0.0057) and age at diagnosis of cystic fibrosis (p = 0.014). CONCLUSIONS: The risk of developing liver disease is higher among patients diagnosed at an early age and those with worse clinical status as assessed by the Shwachman score, indicating that liver involvement might be part of a more severe form of the condition. These patients merit greater attention in terms of screening for liver disease and should be given treatment with ursodeoxycholic acid earlier in the event of abnormal findings.

Sintomas inespecíficos no diagnóstico de leucemia na infância / Vague symptoms in leukemia diagnosis in childhood

As manifestações clínicas de extenso número de doenças, sejam benignas, de cursoauto-limitado, ou malignas, podem ser caracterizadas por sintomatologia inespecífica,como: febre, cefaleia e fadiga. Essas manifestações requerem atenção acurada paraserem surpreendidas e valorizadas para que o diagnóstico da doença que expressamseja feito precocemente. A leucemia mieloblástica aguda (LMA) também pode se apresentarcom sintomatologia inespecífica, exigindo diagnóstico com base na anamnesee exame físico minuciosos. Os principais exames complementares são o hemogramae o mielograma. Este caso descrito ilustra a maneira como o paciente com LMA seapresentou ao Pronto Atendimento e como sua condução foi realizada pela equipe desaúde que o atendeu.

Vague signs and symptoms as fever, headache and fatigue compose the clinical presenta-tion of an extensive number of diseases, from the benign ones, with a self-limited course, to the severe ones. Thus, a proper medical attention is indispensable for early diagnosis of the affections that begins with vague signs and symptoms. The inespecific clinical manifestations also permeates the diagnosis of acute myeloblastic leukemia - AML, whose diagnosis is based on history taking and physical examination. The hemogram and the myelogram are the major exams complementaires. The clinical case described in this article illustrates how the patient with AML has presented himself to the emergency care and the conduction to the case proportionated by the health team that attended him.

Sickle cell disease: a clinical and histopathologic study of the liver in living children.

PURPOSE: To study hepatic lesions in living children with sickle cell disease. Although such lesions are well known, the possibility of chronic persistent damage to the parenchyma resulting from the disease itself or iron overload is controversial. PATIENTS AND METHODS: Sixteen children with sickle cell disease aged 15 months to 18 years were prospectively investigated out of 741 patients younger than 20 years registered at Hemominas Foundation, Brazil. Inclusion criteria for biopsy were as follows: five had positive anti-hepatitis C virus (HCV) antibody, two had positive hepatitis B virus (HBV) surface antigen and persistently increased levels of aminotransferases, and nine underwent biopsy during abdominal surgery. RESULTS: Children with B or C hepatitis were significantly older than the others and also had increased levels of both alanine and aspartate aminotransferases. Lobular architecture was preserved in all nonviral cases; mild to moderate sinusoidal dilatation was present in eight, hepatocellular regenerative activity in six, and focal necrosis and corresponding mild inflammatory infiltrate in three. No fibrosis or bile duct damage was observed. Mild to severe hemosiderosis was present in all children except one. The degree of iron overload was clearly associated with the number of previous blood transfusions. All five children with HCV had chronic hepatitis. One of the children with HBV had incomplete and the other had definite cirrhosis. CONCLUSIONS: These data indicate that chronic hepatic lesions in children with sickle cell disease may be caused by viral damage. Patients without evidence for viral etiology had reversible vascular lesions. Follow-up studies would be necessary to confirm this hypothesis but are precluded for ethical reasons. Hemosiderosis was not associated with fibrosis in any nonviral cases, but a larger number of patients would be necessary to establish valid conclusions.

A criança com hepatopatia crônica: abordagem diagnóstica inicial / The child with chronic liver disease: initial diagnostic approach

Um amplo espectro de doenças hepáticas crônicas pode se manifestar na faixa etária pediátrica, seja ao nascimento, nos primeiros anos de vida ou mais tardiamente. As hepatopatias crônicas acarretam impacto importante na morbimortalidade, o que enfatiza a necessidade de diagnóstico precoce. Este artigo aborda a conduta diagnóstica inicial frente a uma criança com quadro sugestivo de hepatopatia crônica. (AU)

A wide spectrum of chronic liver disease can manifest in childhood: either at birth, in the first few years of life, or later. Chronic Liver disease mean significant impact on mortality and morbidity, thus early diagnosis is very important. This article discusses the initial diagnostic approach of a child with chronic liver disease. (AU)

Doença de Wilson em crianças e adolescentes: como fazer diagnóstico precoce / Wilson's disease in children and adolescent: a key to an early diagnosis

A doença de Wilson é uma desordem autossômica recessiva do metabolismo do cobre, que leva à impregnação desse metal em diversos tecidos como o fígado, cérebro, córnea e rins. Tem prevalência de 1:40.000 e evolui de forma progressiva e fatal se não tratada. Seu diagnóstico depende de suspeição clínica e exames laboratoriais, podendo ser difícil nos pacientes assintomáticos ou com insuficiência hepática grave. A tríade clássica de apresentação é hepática, neurológica e oftalmológica. Na criança, a forma de apresentação mais comum é a hepática (aguda ou crônica). Os critérios diagnósticos são baseados na presença de ceruloplasmina baixa, cobre em urina de 24 horas e cobre livre elevados e avaliação oftalmológica à procura do anel de Kayser-Fleischer. O tratamento medicamentoso deve ser instituído o quanto antes, de forma a evitaremse as lesões teciduais do excesso de cobre, daí a grande importância do diagnóstico precoce. A droga de escolha é a D-penicilamina, mas é necessário o monitoramento de seus possíveis efeitos colaterais e eventuais pioras do quadro neuropsiquiátrico. Existem outras drogas, como a trientina, tetratiomolibdato e o zinco, que também têm efeito na redução do cobre orgânico. (AU)

Wilson disease is an authossomal recessive disorder of copper metabolism that leads to the impregnation of the metal in different tissues such as the liver, brain, cornea and kidneys. There is a prevalence of 1:40,000 and evolution is progressive and fatal if untreated. The diagnosis depends on clinical suspicion and laboratory tests, and may be difficult in situations such as the asymptomatic patients or with severe liver insufficiency. The classic triad presentation is the hepatic, neurological and ophthalmologic disease. In children, the most common is the hepatic (acute or chronic). The diagnosis criteria are based on the presence of low ceruloplasmine, elevated copper in 24-hour urine and high seric copper and ophthalmologic evaluation in search of Kayser Fleischer ring. The medication treatment must be established as soon as possible so as to prevent tissue lesions due to copper excess, hence the great importance of early diagnosis. The drug choice is the D-penicilamin, with careful monitoring of side effects and attention for occasional worsening of the neuropsychiatric state. There are other drugs as trientine, tetratiomolibdato and zinc that also have an effect on the reduction of organic copper. (AU)

Transplante hepático pediátrico: experiência de 10 anos em um único centro no Brasil / Pediatric liver transplantation: 10 years of experience at a single center in Brazil

OBJETIVOS: Avaliar a experiência dos primeiros 10 anos de transplante hepático em crianças e adolescentes do Serviço de Transplante Hepático do Instituto Alfa de Gastroenterologia do Hospital das Clínicas da Universidade Federal de Minas Gerais. MÉTODOS: Estudo descritivo de 84 pacientes menores de 18 anos inscritos em lista para transplante, no período de março de 1995 a janeiro de 2006, quanto às seguintes variáveis: idade, indicação do transplante, escores de gravidade (Child-Pugh, Malatack, PELD/MELD), tempo de espera em lista, complicações pós-operatórias e sobrevida. RESULTADOS: De 84 pacientes inscritos, 40 foram submetidos ao transplante, ocorrendo dois retransplantes. Vinte e seis faleceram na lista de espera. A atresia biliar foi a indicação mais freqüente. A mediana da idade no momento do transplante foi de 6,6 anos (variou de 1,9 a 16,8 anos). A mortalidade no pós-transplante foi de 32,5 por cento (13 de 40 crianças). O tempo de espera em lista dos 40 pacientes transplantados apresentou mediana de 291 dias. As complicações relacionadas ao enxerto ocorreram em 24 dos 42 transplantes (57,1 por cento), sendo que as vasculares representaram 30,8 por cento, prevalecendo a trombose da artéria hepática (16,6 por cento); episódio de rejeição aguda ocorreu em 16,6 por cento dos casos. CONCLUSÃO: Os resultados encontrados são semelhantes ao que é observado na literatura em relação às indicações e sobrevida no pós-transplante. No entanto, houve elevada taxa de complicações não relacionadas ao enxerto e daquelas relacionadas à artéria hepática.

OBJECTIVES: To evaluate the first 10 years' experience of the liver transplantation department at the Alfa Institute, Hospital das Clínicas da Universidade Federal de Minas Gerais, Brazil. METHODS: A descriptive study, based on a retrospective analysis of 84 children and adolescents enrolled on a liver transplantation waiting list, from March 1995 to January 2006, based on the following variables: age, etiology of underlying liver disease, Child-Pugh, Malatack, model for end-stage liver disease (MELD) and pediatric end-stage liver disease (PELD) scores, time on waiting list, complications and survival after the procedure. RESULTS: Forty children had 42 liver transplants. Twenty six died while on the waiting list. Biliary atresia was the most frequent indication for transplant. The median age was 6.6 years (ranging from 1.9 to 16.8 years). Post liver transplant mortality was 32.5 percent (13 of 40 children). The median time on the liver transplant waiting list was 291 days. Complications related to the graft occurred in 24 of 42 transplants (57.1 percent), including vascular complications (30.8 percent), with thrombosis of the hepatic artery being the most frequent (16.6 percent); acute rejection occurred in 16.6 percent. CONCLUSIONS: The overall results are similar to what can be found in the literature with relation to indications and post-transplant survival. However, there were elevated rates of complications unrelated to the graft and of complications involving the hepatic artery.

Hepatite auto-imune tipo 1 em crianças e adolescentes: avaliação da suspensão do tratamento imunossupressor / Type 1 autoimmune hepatitis in children and adolescents: assessment of immunosuppressive treatment withdrawal

OBJETIVO: Avaliar a suspensão do tratamento em crianças e adolescentes com hepatite auto-imune em remissão clínica e laboratorial, por um período mínimo de 24 meses, avaliando o índice de recaída após a suspensão do tratamento. MÉTODO: É um estudo descritivo, retrospectivo e parcialmente prospectivo de 21 crianças e adolescentes com hepatite auto-imune tipo 1, atendidos no Ambulatório de Hepatologia Pediátrica do Hospital das Clínicas da Universidade Federal de Minas Gerais (UFMG), no período de janeiro de 1986 a dezembro de 2001. RESULTADOS: Foram avaliados 54 pacientes, dos quais 21 foram selecionados, sendo 19 do sexo feminino (90,5 por cento), com idade variando de 5,7 a 17,6 anos (mediana de 13,8 anos), tempo médio de seguimento de 5,1±2,4 anos (mediana 4,4 anos) e remissão clínica e laboratorial por um tempo médio de 4,1±1,5 anos (mediana 3,8 anos). Dos 21 pacientes avaliados, 10 (47,6 por cento) ainda apresentavam atividade inflamatória, impossibilitando a suspensão do tratamento, o qual foi interrompido em 11 pacientes (52,4 por cento). Desses, seis pacientes (54,5 por cento) apresentaram reativação da doença, e cinco mantêm remissão clínica e laboratorial, com tempo médio de seguimento de 4±1 anos (mediana 3,9 anos). O intervalo de tempo entre a suspensão do tratamento e a reativação da doença variou de 29 dias a 40,3 meses (mediana 2,2 meses). CONCLUSÕES: Nesse grupo de pacientes com hepatite auto-imune, foi observado alto índice de recaídas (54,5 por cento), que ocorreram com maior freqüência nos primeiros 12 meses pós-suspensão do tratamento, além de grande número de pacientes que apresentou algum grau de atividade inflamatória, apesar do longo tempo de remissão clínico-laboratorial.

Diagnóstico da atresia biliar por meio da ultra-sonografia e da histopatologia / Diagnosis of biliary atresia by ultrasonographic exams and histopathology

A atresia biliar representa um dos maiores desafios da hepatologia pediátrica, por se tratar de afecção que tem semelhança clínica e laboratorial com outras doenças colestáticas do período neonatal, com indicação cirúrgica antes dos 60 dias de vida. Este trabalho tem como objetivo apresentar uma revisão sobre o diagnóstico ultra-sonográfico e histopatológico dessa afecção.

Colestase neonatal / Neonatal cholestasis

Objetivo: Alertar o pediatria a respeito da importância do conhecimento precoce da colestase do recém-nascido e do lactente. Métodos: Realizou-se um levantameto bibliográfico, através do Medline, acerca do tema colestase com destaque para as publicações mais relevantes dos últimos 30 anos. Resultados: São descritos o conceito de colestase e os motivos da propensão colestática inerentes ao recém-nascido e ao lactente. As diversas causas de colestase intra e extra-hepáticas estão relacionadas. Nesta revisão, são comentadas apenas aquelas afecções que apresentam particularidades diagnósticas, terapêuticas ou prognósticas, como a atresia biliar extra-hepática, hepatite neonatal idiopática, galactosemia, síndrome de Alagille, dentre outras. Além disso, são discutidos os diversos recursos propedêuticos para o diagnóstico das causas de colestase. Conclusões: O estabelecimento do diagnóstico de colestase, através da detecção da hiperbilirrubinemia direta nos recém-nascidos que permanecem ictéricos após os 14 dias de vida, constitui uma meeta que pode mudar o prognóstico das várias doenças responsáveis pela colestase neonatal