Recurrence of Primary Sclerosing Cholangitis After Liver Transplant in Children: An International Observational Study.

BACKGROUND AND AIMS: Recurrent primary sclerosing cholangitis (rPSC) following liver transplant (LT) has a negative impact on graft and patient survival; little is known about risk factors for rPSC or disease course in children. APPROACH AND RESULTS: We retrospectively evaluated risk factors for rPSC in 140 children from the Pediatric PSC Consortium, a multicenter international registry. Recipients underwent LT for PSC and had >90 days of follow-up. The primary outcome, rPSC, was defined using Graziadei criteria. Median follow-up after LT was 3 years (interquartile range 1.1-6.1). rPSC occurred in 36 children, representing 10% and 27% of the subjects at 2 years and 5 years following LT, respectively. Subjects with rPSC were younger at LT (12.9 vs. 16.2 years), had faster progression from PSC diagnosis to LT (2.5 vs. 4.1 years), and had higher alanine aminotransferase (112 vs. 66 IU/L) at LT (all P < 0.01). Inflammatory bowel disease was more prevalent in the rPSC group (86% vs. 66%; P = 0.025). After LT, rPSC subjects had more episodes of biopsy-proved acute rejection (mean 3 vs. 1; P < 0.001), and higher prevalence of steroid-refractory rejection (41% vs. 20%; P = 0.04). In those with rPSC, 43% developed complications of portal hypertension, were relisted for LT, or died within 2 years of the diagnosis. Mortality was higher in the rPSC group (11.1% vs. 2.9%; P = 0.05). CONCLUSIONS: The incidence of rPSC in this cohort was higher than previously reported, and was associated with increased morbidity and mortality. Patients with rPSC appeared to have a more aggressive, immune-reactive phenotype. These findings underscore the need to understand the immune mechanisms of rPSC, to lay the foundation for developing new therapies and improve outcomes in this challenging population.

Case presentation methods: a randomized controlled trial of the one-minute preceptor versus SNAPPS in a controlled setting.

INTRODUCTION: One-minute preceptor (OMP) and SNAPPS (a mnemonic for Summarize history and findings; Narrow the differential; Analyze the differential; Probe the preceptor about uncertainties; Plan management; and Select case-related issues for self-study) are educational techniques developed to promote learners' expression of clinical reasoning during the case presentation in the workplace. The aim of this present study was to compare the content of the case presentation between the SNAPPS and the OMP methods. METHODS: This was a randomized controlled trial comparing SNAPPS and OMP in 60 medical students at the beginning of their fifth year of medical school. After an introduction session, students presented and discussed two cases based on real patients and provided in written format. All case presentations were recorded and evaluated by two researchers. The assessed elements of the case presentations were divided into three subgroups related to expression of clinical reasoning, time and initiative to guide the presentation. RESULTS: There were 30 participants in each group. There was no difference in the expression of clinical reasoning between OMP and SNAPPS groups (number of differential diagnoses, justification of most likely diagnosis and differential diagnosis, expression of comparing and contrasting hypotheses). However, students in the SNAPPS group expressed significantly more questions and uncertainties (p < 0.001), and more often took the initiative to present and justify the most likely diagnosis, differential diagnosis and management plan than students in the OMP group, both in simple and complex cases (all p values <0.001) without extending the length of the teaching session. CONCLUSION: OMP and SNAPPS equally promote medical students' expression of clinical reasoning. The SNAPPS technique was more effective than the OMP technique in helping students to take on an active role during case presentation. We propose SNAPPS as an effective learning tool, engaging students and promoting the expression of their clinical reasoning as part of a case presentation.

Histological evolution of fibrosis in patients with biliary atresia / Evolução histológica da fibrose em pacientes com atresia biliar

ABSTRACT Objective: To evaluate the evolution of histological findings of patients with biliary atresia (BA), emphasizing the progression of fibrosis by comparing the diagnostic liver biopsy to the surgical liver biopsy, performed during Kasai portoenterostomy. Methods: Retrospective study with 51 patients with BA submitted to portoenterostomy, and both diagnostic (DLB) and surgical liver biopsies (SLB). The samples were blindly reviewed by two pathologists. Results: Median age at DLB and at SLB was 69 and 77 days, respectively. The median time between biopsies was eight days. Cirrhosis was more frequent in SLB than in DLB, both according to the Metavir score (p = 0.006) and the Ishak score (p = 0.016). The Metavir score increased one or more points in 29/51 (56.9%), with evidence of progression to liver cirrhosis in 11/29 (37.9%) of those who had progression of fibrosis. Median age at surgery of those who had a progression of fibrosis was 77 days, while in those 11 who progressed to cirrhosis, this median was 92 days. Cirrhosis was seen in 12/51 (23.5%) SLB patients. The clinical variable age at surgery had a statistically significant difference regarding the presence or absence of cirrhosis in SLB (p = 0.024). Cirrhosis was not related to survival with native liver or biliary drainage. Conclusion: Most infants with BA have liver fibrosis at diagnosis and it progresses rapidly. The presence of cirrhosis is correlated with the age at surgery, which suggests the importance of this clinical variable in the evolution of fibrosis.

RESUMEN Objetivo: Analizar la evolución de los hallazgos histológicos de pacientes con atresia de vías biliares (AVB), resaltando la progresión de la fibrosis y comparando la biopsia hepática diagnóstica (BHD) con la biopsia hepática quirúrgica (BHQ) mediante la hepatoportoenterostomía de Kasai. Método: Estudio retrospectivo con 51 pacientes con AB sometidos a hepatoportoenterostomía, BHD y BHQ. Resultados: La edad mediana para BHD y BHQ fue 69 días y 77 días, respectivamente. El tiempo mediano entre las biopsias fue ocho días. La cirrosis fue más frecuente en la BHQ de lo que en la BHD, tanto de acuerdo con el escore de Metavir (p = 0,006) como con el escore de Ishak (p = 0,016). El escore de Metavir aumentó un punto o más en 29/51 (59,9%) pacientes, con evidencias de progresión hacia cirrosis hepática en 11/29 (37,9%), en los pacientes con progresión de la fibrosis. La edad mediana para cirugía de los que tuvieron progresión de la fibrosis fue 77 días; en los 11 que evolucionaron hacia cirrosis, esa mediana fue 92 días. La variable clínica de edad en el momento de la cirugía presentó diferencia estadísticamente significante con respecto a la presencia o ausencia de cirrosis (p = 0,024). La cirrosis no fue asociada a la sobrevida con hígado nativo o drenaje biliar. Conclusión: La mayor parte de los niños con AVB tiene fibrosis hepática en el momento del diagnóstico, y la enfermedad avanza rápidamente. La presencia de cirrosis está relacionada con la edad al momento de la cirugía, lo que sugiere la importancia de esa variable clínica en la evolución de la fibrosis.

RESUMO Objetivo: Avaliar a evolução dos achados histológicos de pacientes com atresia biliar (AB), enfatizando a progressão da fibrose e comparando a biópsia hepática diagnóstica (BHD) com a biópsia hepática cirúrgica (BHC), realizada durante a portoenterostomia de Kasai. Método: Estudo retrospectivo com 51 pacientes portadores de AB submetidos a portoenterostomia, BHD e BHC. Resultados: A idade mediana para BHD e BHC foi de 69 e 77 dias de idade, respectivamente. O tempo mediano entre as biópsias foi de oito dias. A cirrose foi mais frequente na BHC do que na BHD, tanto de acordo com o escore de Metavir (p = 0,006) quanto com o escore de Ishak (p = 0,016). O escore de Metavir aumentou um ou mais pontos em 29/51 (56,9%) pacientes, com evidências de progressão para cirrose hepática em 11/29 (37,9%), naqueles com progressão da fibrose. A idade mediana para cirurgia dos que tiveram progressão da fibrose foi de 77 dias; nos 11 que evoluíram para cirrose, essa mediana foi de 92 dias. A variável clínica da idade no momento da cirurgia apresentou diferença estatisticamente significativa em relação à presença ou à ausência de cirrose (p = 0,024). A cirrose não foi associada à sobrevida com fígado nativo ou drenagem biliar. Conclusão: A maioria das crianças com AB tem fibrose hepática no momento do diagnóstico, e a doença progride rapidamente. A presença de cirrose está correlacionada com a idade à cirurgia, o que sugere a importância dessa variável clínica na evolução da fibrose.

Autoimmune hepatitis in 828 Brazilian children and adolescents: clinical and laboratory findings, histological profile, treatments, and outcomes / Hepatite autoimune em 828 crianças e adolescentes brasileiros: achados clínicos e laboratoriais, perfil histológico, tratamentos e resultados

Abstract Objective: This large study with a long-term follow-up aimed to evaluate the clinical presentation, laboratory findings, histological profile, treatments, and outcomes of children and adolescents with autoimmune hepatitis. Methods: The medical records of 828 children and adolescents with autoimmune hepatitis were reviewed. A questionnaire was used to collect anonymous data on clinical presentation, biochemical and histological findings, and treatments. Results: Of all patients, 89.6% had autoimmune hepatitis-1 and 10.4% had autoimmune hepatitis-2. The female sex was predominant in both groups. The median age at symptom onset was 111.5 (6; 210) and 53.5 (8; 165) months in the patients with autoimmune hepatitis 1 and autoimmune hepatitis-2, respectively. Acute clinical onset was observed in 56.1% and 58.8% and insidious symptoms in 43.9% and 41.2% of the patients with autoimmune hepatitis-1 and autoimmune hepatitis-2, respectively. The risk of hepatic failure was 1.6-fold higher for autoimmune hepatitis-2. Fulminant hepatic failure occurred in 3.6% and 10.6% of the patients with autoimmune hepatitis-1 and autoimmune hepatitis-2, respectively; the risk was 3.1-fold higher for autoimmune hepatitis-2. The gamma globulin and immunoglobulin G levels were significantly higher in autoimmune hepatitis-1, while the immunoglobulin A and C3 levels were lower in autoimmune hepatitis-2. Cirrhosis was observed in 22.4% of the patients; biochemical remission was achieved in 76.2%. The actuarial survival rate was 93.0%. A total of 4.6% underwent liver transplantation, and 6.9% died (autoimmune hepatitis-1: 7.5%; autoimmune hepatitis-2: 2.4%). Conclusions: In this large clinical series of Brazilian children and adolescents, autoimmune hepatitis-1 was more frequent, and patients with autoimmune hepatitis-2 exhibited higher disease remission rates with earlier response to treatment. Patients with autoimmune hepatitis-1 had a higher risk of death.

Resumo Objetivo: Este estudo com acompanhamento de longo prazo visou a avaliar o quadro clínico, os achados laboratoriais, o perfil histológico, os tratamentos e os resultados de crianças e adolescentes com hepatite autoimune. Métodos: Foram analisados os prontuários médicos de 828 crianças e adolescentes com HAI. Foi usado um questionário para coletar os dados anônimos sobre o quadro clínico, os achados bioquímicos e histológicos e os tratamentos. Resultados: De todos os pacientes, 89,6% tinham hepatite autoimune-1 e 10,4% hepatite autoimune-2. O sexo feminino foi predominante nos dois grupos. A idade média no início dos sintomas foi 111,5 (6; 210) e 53,5 (8; 165) meses nos pacientes com hepatite autoimune-1 e hepatite autoimune-2, respectivamente. Foi observado início clínico agudo em 56,1% e 58,8% e sintomas insidiosos em 43,9% e 41,2% dos pacientes com hepatite autoimune-1 e hepatite autoimune-2, respectivamente. A probabilidade de insuficiência hepática foi 1,6 vezes maior para hepatite autoimune-2; 3,6% e 10,6% dos pacientes com hepatite autoimune-1 e hepatite autoimune-2, respectivamente, apresentaram insuficiência hepática fulminante; o risco foi 3,1 vezes maior para hepatite autoimune-2. Os níveis de gamaglobulina e imunoglobulina G foram significativamente maiores nos pacientes com hepatite autoimune-1, ao passo que os níveis de imunoglobulina A e C3 foram menores em pacientes com hepatite autoimune-2; 22,4% dos pacientes apresentaram cirrose e a remissão bioquímica foi atingida em 76,2%. A taxa de sobrevida atuarial foi de 93,0%. Um total de 4,6% pacientes foram submetidos a transplante de fígado e 6,9% morreram (hepatite autoimune-1: 7,5%; hepatite autoimune-2: 2,4%). Conclusões: Nesta grande série clínica de crianças e adolescentes brasileiros, a hepatite autoimune-1 foi mais frequente e os pacientes com hepatite autoimune-2 mostraram maiores taxas de remissão da doença com respostas mais rápidas aos tratamentos. Os pacientes com hepatite autoimune-1 apresentaram maior risco de óbito.

Autoimmune hepatitis in 828 Brazilian children and adolescents: clinical and laboratory findings, histological profile, treatments, and outcomes.

OBJECTIVE: This large study with a long-term follow-up aimed to evaluate the clinical presentation, laboratory findings, histological profile, treatments, and outcomes of children and adolescents with autoimmune hepatitis. METHODS: The medical records of 828 children and adolescents with autoimmune hepatitis were reviewed. A questionnaire was used to collect anonymous data on clinical presentation, biochemical and histological findings, and treatments. RESULTS: Of all patients, 89.6% had autoimmune hepatitis-1 and 10.4% had autoimmune hepatitis-2. The female sex was predominant in both groups. The median age at symptom onset was 111.5 (6; 210) and 53.5 (8; 165) months in the patients with autoimmune hepatitis 1 and autoimmune hepatitis-2, respectively. Acute clinical onset was observed in 56.1% and 58.8% and insidious symptoms in 43.9% and 41.2% of the patients with autoimmune hepatitis-1 and autoimmune hepatitis-2, respectively. The risk of hepatic failure was 1.6-fold higher for autoimmune hepatitis-2. Fulminant hepatic failure occurred in 3.6% and 10.6% of the patients with autoimmune hepatitis-1 and autoimmune hepatitis-2, respectively; the risk was 3.1-fold higher for autoimmune hepatitis-2. The gamma globulin and immunoglobulin G levels were significantly higher in autoimmune hepatitis-1, while the immunoglobulin A and C3 levels were lower in autoimmune hepatitis-2. Cirrhosis was observed in 22.4% of the patients; biochemical remission was achieved in 76.2%. The actuarial survival rate was 93.0%. A total of 4.6% underwent liver transplantation, and 6.9% died (autoimmune hepatitis-1: 7.5%; autoimmune hepatitis-2: 2.4%). CONCLUSIONS: In this large clinical series of Brazilian children and adolescents, autoimmune hepatitis-1 was more frequent, and patients with autoimmune hepatitis-2 exhibited higher disease remission rates with earlier response to treatment. Patients with autoimmune hepatitis-1 had a higher risk of death.

Autoimmune Hepatitis and Autoimmune Hepatitis Overlap With Sclerosing Cholangitis: Immunophenotype Markers in Children and Adolescents.

OBJECTIVE: The pathophysiology of autoimmune hepatitis (AIH) may involve the activation of immune cells and changes in the expression of cellular markers. The aim of the present study was to characterize the immunophenotype markers of lymphocytes and monocytes in the peripheral blood of children and adolescents with type 1 AIH and AIH overlap with sclerosing cholangitis (overlap syndrome [OS]). METHODS: This is a cross-sectional study of 20 children and adolescents diagnosed with type 1 AIH and 19 with OS. Fifteen healthy subjects were included as controls. Flow cytometric analysis was used to identify markers of inflammation and autoimmunity. RESULTS: The total number of CD4 T cells was higher in the AIH patients compared with the controls. The number of CD4 T cells expressing CCR3 and CD28 was higher in the AIH group than in the control group. CD45RO was more highly expressed in the AIH group, whereas CD45RA was more highly expressed in the OS group. In regard to CD8 T lymphocytes, the CCR3 expression was higher in both groups of patients. Patients with OS had the highest expression of CD45RA and CD25. In monocytes, human leukocyte antigen DR (HLA-DR) was less expressed in both groups of patients. CONCLUSIONS: Complex phenotype features may be involved in the pathophysiology of AIH, accounting for changes in immune system regulation mechanisms. In conclusion, even after good response to treatment, patients still have immune activity signals at the cellular level.

Factors Associated With Bleeding Secondary to Rupture of Esophageal Varices in Children and Adolescents With Cirrhosis.

OBJECTIVE: Bleeding of esophageal varices is the main cause of morbidity and mortality in children with portal hypertension. It is important to understand the factors related with a bleeding episode to evaluate more effective primary prophylaxis. The present study aims to describe the endoscopic and laboratory findings associated with upper gastrointestinal bleeding (UGIB) secondary to esophageal varices. METHOD: A cross-sectional study with 103 children and adolescents with cirrhosis, divided into a group that had experienced an episode of upper UGIB (35 patients) and a group without a history of UGIB (68 patients), was carried out. The esophageal and gastric varices were classified, and the portal hypertensive gastropathy, laboratory findings, and Child-Pugh classification were measured. RESULTS: Factors observed in univariate analysis to be associated with UGIB were the presence of esophageal varices of medium caliber or larger, portal hypertensive gastropathy, presence of red spots on esophageal varices, Child-Pugh class B or C, and hypoalbuminemia (P < 0.05). After multivariate logistic regression analysis, the significant factors were the presence of red spots on esophageal varices and the presence of gastric varices. When separated the autoimmune hepatitis, nonbiliary atresia patients (all patients except the patients with biliary atresia), and biliary atresia groups the findings in the univariate analysis were the presence of esophageal varices of medium or larger caliber, presence of red spots on varices, and presence of gastric varices in the autoimmune hepatitis patients and nonbiliary atresia patients and presence of red spots on esophageal varices, presence of gastric varices, and Child-Pugh classification B or C in biliary atresia group (P < 0.05). After multivariate logistic regression analysis, no statistical significance was found for any factor analyzed in any groups. CONCLUSIONS: The presence of gastric varices and red spots on esophageal varices were related to episodes of UGIB secondary to rupture of esophageal varices. When these findings are observed, indications for endoscopic primary prophylaxis should be evaluated. More studies are, however, necessary to better understand this problem.

Clinical Characteristics and Prognosis in Children and Adolescents With Autoimmune Hepatitis and Overlap Syndrome.

OBJECTIVES: This is a cohort study of 134 children and adolescents with a known diagnosis of autoimmune hepatitis (AIH). During follow-up, some of them developed autoimmune sclerosing cholangitis (ASC). This study describes the characteristics of the patients upon diagnosis, and their response to treatment and any complications, and compares the patients who developed ASC during follow-up (ASC group) with those who did not (AIH group). METHODS: A total of 73.1% of the patients were girls with a median age upon diagnosis of 10.41 (7.41-12.53) years. RESULTS: Of 134 patients, 28 (20.9%) developed cholestatic manifestations, with features of ASC. A few differences were observed between the AIH and ASC groups when they were analyzed by χ test, such as the smaller predominance of girls in ASC group (P = 0.04), and more common asymptomatic presentation in the ASC group (P = 0.01). Cirrhosis was observed in 68% of biopsies, with no significant difference between groups (P = 0.43). Of 16 deaths, 15 were in the AIH group and 1 in the ASC group (P = 0.22). Of 11 transplants, 10 were in the AIH group and one in the ASC group (P = 0.53). The presence of cirrhosis at baseline was associated with a smaller survival probability (P = 0.015). The survival rate by Kaplan-Meier method was 94% at 5 years and 80% at 10 years, and was similar in both the groups (P = 0.08). CONCLUSIONS: No statistically significant difference was observed between the groups in relation to prognosis and response to treatment.

Accuracy of echogenic periportal enlargement image in ultrasonographic exams and histopathology in differential diagnosis of biliary atresia.

OBJECTIVES: To define the sensitivity, specificity and accuracy of the ultrasound triangular cord sign and hepatic histopathology, in isolation or in combination, for diagnostic differentiation between biliary atresia and intrahepatic cholestasis. METHODS: This was a retrospective study carried out between January 1990 and December 2004. Fifty-one cases of biliary atresia and 45 of intrahepatic cholestasis were analyzed. Histopathology was performed blind by a pathologist. The triangular cord sign was identified in ultrasound reports as the only diagnostic sign of biliary atresia. Sensitivity, specificity and accuracy were calculated for the triangular cord sign and histology both in isolation and in combination. The gold standard for diagnosis of biliary atresia was the appearance of the extrahepatic biliary tree via laparotomy. RESULTS: The triangular cord sign alone had sensitivity of 49%, specificity of 100% and accuracy of 72.5%. Histopathology compatible with extrahepatic biliary obstruction alone had 90.2% sensitivity, 84.6% specificity and 87.8% accuracy. The triangular cord sign and histopathology in isolation or combination resulted in sensitivity of 93.2%, specificity of 85.7% and accuracy of 90.3%. CONCLUSIONS: Finding the triangular cord sign on ultrasound is an indication for laparotomy. If the triangular cord sign is negative, liver biopsy is indicated; if histopathology reveals signs of biliary atresia, explorative laparotomy is indicated. In cases where the triangular cord sign is absent and histopathology indicates neonatal hepatitis or other intrahepatic cholestasis, clinical treatment or observation are recommended in accordance with the diagnosis.

Acurácia diagnóstica do espessamento ecogênico periportal à ultra-sonografia e da histopatologia no diagnóstico diferencial da atresia biliar / Accuracy of echogenic periportal enlargement image in ultrasonographic exams and histopathology in differential diagnosis of biliary atresia

OBJETIVOS: Definir a sensibilidade, especificidade e a acurácia do espessamento ecogênico periportal à ultra-sonografia e da histopatologia hepática, isolados ou em conjunto, na distinção diagnóstica entre atresia biliar e as colestases intra-hepáticas. MÉTODOS: Trata-se de estudo retrospectivo realizado entre janeiro de 1990 e dezembro de 2004. Foram analisados 51 casos de atresia biliar e 45 com colestase intra-hepática. A histopatologia foi realizada por uma patologista de forma cega. O espessamento ecogênico periportal foi pesquisado na ultra-sonografia como único sinal diagnóstico de atresia biliar. Foram calculados os índices de sensibilidade, especificidade e acurácia do espessamento ecogênico periportal e da histologia isoladamente ou associados. O padrão-ouro utilizado para o diagnóstico de atresia biliar foi o aspecto da via biliar extra-hepática à laparotomia. RESULTADOS: O espessamento ecogênico periportal revelou sensibilidade de 49 por cento, especificidade de 100 por cento e acurácia de 72,5 por cento. A histopatologia compatível com obstrução biliar extra-hepática conferiu sensibilidade de 90,2 por cento, especificidade de 84,6 por cento e acurácia de 87,8 por cento. O espessamento ecogênico periportal e a histopatologia isolados ou associados proporcionaram sensibilidade de 93,2 por cento, especificidade de 85,7 por cento e acurácia de 90,3 por cento. CONCLUSÕES: A evidência do espessamento ecogênico periportal na ultra-sonografia é indicação de laparotomia. Se o espessamento ecogênico periportal é negativo, está indicada a biopsia hepática; se a histopatologia revelar sinais de atresia biliar, impõe-se a laparotomia exploradora. Nos casos de espessamento ecogênico periportal negativo com histopatologia de hepatite neonatal ou de outras colestases intra-hepáticas, recomenda-se o acompanhamento ou o tratamento clínico conforme o diagnóstico.

OBJECTIVES: To define the sensitivity, specificity and accuracy of the ultrasound triangular cord sign and hepatic histopathology, in isolation or in combination, for diagnostic differentiation between biliary atresia and intrahepatic cholestasis. METHODS: This was a retrospective study carried out between January 1990 and December 2004. Fifty-one cases of biliary atresia and 45 of intrahepatic cholestasis were analyzed. Histopathology was performed blind by a pathologist. The triangular cord sign was identified in ultrasound reports as the only diagnostic sign of biliary atresia. Sensitivity, specificity and accuracy were calculated for the triangular cord sign and histology both in isolation and in combination. The gold standard for diagnosis of biliary atresia was the appearance of the extrahepatic biliary tree via laparotomy. RESULTS: The triangular cord sign alone had sensitivity of 49 percent, specificity of 100 percent and accuracy of 72.5 percent. Histopathology compatible with extrahepatic biliary obstruction alone had 90.2 percent sensitivity, 84.6 percent specificity and 87.8 percent accuracy. The triangular cord sign and histopathology in isolation or combination resulted in sensitivity of 93.2 percent, specificity of 85.7 percent and accuracy of 90.3 percent. CONCLUSIONS: Finding the triangular cord sign on ultrasound is an indication for laparotomy. If the triangular cord sign is negative, liver biopsy is indicated; if histopathology reveals signs of biliary atresia, explorative laparotomy is indicated. In cases where the triangular cord sign is absent and histopathology indicates neonatal hepatitis or other intrahepatic cholestasis, clinical treatment or observation are recommended in accordance with the diagnosis.

Portal vein thrombosis in children and adolescents.

OBJECTIVE: To review the literature on portal vein thrombosis in children and adolescents, focusing on its diagnosis, complications and treatment. SOURCES OF DATA: The medical literature of the past 10 years was reviewed using the PubMed and MEDLINE search engines, with major focus on portal vein thrombosis and its clinical outcomes. The following keywords or expressions were used for the web search: portal vein thrombosis, extra-hepatic portal vein obstruction, prognosis, children, portal hypertension, esophagogastric varices. Additionally, we also reviewed the articles cited in the references of the initially selected papers, as well as relevant textbooks. SUMMARY OF THE FINDINGS: Portal vein thrombosis is one of the most common causes of portal hypertension among children. The initial clinical manifestation is characterized either by episodes of upper gastrointestinal bleeding or by splenomegaly on routine clinical examination. The major complications include upper gastrointestinal bleeding, hypersplenism secondary to splenomegaly, growth retardation, and portal biliopathy. The diagnosis is made by abdominal Doppler ultrasonography. Treatment is targeted at the complications and includes primary and secondary prophylaxis against upper gastrointestinal bleeding (which results from the rupture of esophageal varices), and portosystemic shunting in selected cases. CONCLUSIONS: Portal vein thrombosis is one of the major triggers of upper gastrointestinal bleeding in children. Bleeding episodes have a remarkable effect on the quality of life of affected patients. Thus, appropriate diagnosis and treatment are needed in order to reduce morbidity and mortality.

Trombose de veia porta em crianças e adolescentes / Portal vein thrombosis in children and adolescents

OBJETIVO: Apresentar uma revisão atualizada de trombose de veia porta na infância e adolescência, enfatizando o diagnóstico, suas complicações e tratamento. FONTE DOS DADOS: Foi realizada revisão da literatura, dos últimos 10 anos, através de pesquisa bibliográfica na Internet nos principais sites de busca médica, como o PubMed e MEDLINE, com enfoque na doença trombose de veia porta e suas repercussões clínicas. As principais palavras-chave e expressões pesquisadas foram: portal vein thrombosis, extra-hepatic portal vein obstruction, prognosis, children, portal hypertension, esophagogastric varices. Além disso, foram consultados os artigos citados nas referências dos trabalhos selecionados na pesquisa inicial e dos livros textos. SíNTESE DOS DADOS: A trombose de veia porta é uma das causas mais comuns de hipertensão porta na infância. A apresentação clínica inicial pode ser através de episódios de hemorragia digestiva ou da presença de esplenomegalia em exame clínico de rotina. As principais complicações são a hemorragia digestiva, hiperesplenismo secundário à esplenomegalia, retardo de crescimento e biliopatia portal. O diagnóstico é realizado através da ultra-sonografia abdominal com Doppler. O tratamento é direcionado para as complicações, incluindo profilaxia primária e secundária de hemorragia digestiva, conseqüente à ruptura de varizes esofágicas, e derivações porto-sistêmicas, em casos selecionados. CONCLUSÕES:A trombose de veia porta é uma das causas mais importantes de hemorragia digestiva em crianças. Esses episódios acarretam impacto importante na qualidade de vida dos pacientes acometidos. Dessa forma, uma abordagem diagnóstica e terapêutica adequada é desejável na tentativa de se 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.

[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.

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

OBJETIVO: Identificar os fatores de risco associados à hepatopatia da fibrose cística. MÉTODOS: Dos 106 pacientes acompanhados regularmente no ano de 1999, 10 preencheram os critérios clínicos, bioquímicos e/ou ultra-sonográficos para hepatopatia (9,4 por cento). Foram obtidos dos pacientes, no protocolo do serviço à admissão, fatores relacionados aos dados demográficos, genótipo, idade e manifestações ao diagnóstico da fibrose cística, estado nutricional e dados laboratoriais. As variáveis associadas à hepatopatia foram inicialmente identificadas pelo método de Kaplan-Meier. Os fatores significativos na análise univariada foram incluídos na análise multivariada, utilizando o modelo de regressão de Cox. RESULTADOS: Os fatores associados à hepatopatia na análise univariada foram: sexo masculino, idade ao diagnóstico da fibrose cística, insuficiência pancreática, escore z de peso à admissão, escore de Shwachman e bioquímica à admissão. Após o ajustamento pelo modelo de Cox, duas variáveis demonstraram estar independentemente associadas ao desenvolvimento de hepatopatia: escore de Shwachman (p = 0,0057) e idade ao diagnóstico da fibrose cística (p = 0,014). CONCLUSÃO:O risco de hepatopatia é maior entre os pacientes que apresentam diagnóstico mais precoce e entre aqueles com pior estado clínico avaliado pelo escore de Shwachman, evidenciando que a hepatopatia parece fazer parte de uma forma mais grave da doença. Esses pacientes merecem mais atenção quanto ao screening para hepatopatia e instituição mais precoce do ácido ursodesoxicólico na ocorrência de alterações.

[Validation of the Williams ultrasound scoring system for the diagnosis of liver disease in cystic fibrosis]. / Validação do escore ultra-sonográfico de Williams para o diagnóstico da hepatopatia da fibrose cística.

OBJECTIVES: To describe the hepatic abnormalities revealed by ultrasound examination of cystic fibrosis (CF) patients followed at the CF Outpatient Clinic at the Federal University of Minas Gerais; to compare ultrasound data with clinical and biochemical parameters; to validate the Williams ultrasound score for the diagnosis of liver disease in CF. METHODS: Seventy cystic fibrosis patients were followed prospectively and underwent clinical, biochemical and ultrasound examinations. The ultrasound findings were compared to the results of the clinical and biochemical examinations. Clinical and biochemical criteria were used as the gold standard for the validation of the Williams ultrasound score. We calculated the sensitivity, specificity, and positive and negative predictive values for the Williams score. The patients were divided into two groups: normal (score = 3) or abnormal (score > 3) ultrasound examination. RESULTS: Ten patients met the clinical and/or biochemical criteria for liver disease (14.3%). All of them presented some abnormality on ultrasound examination of the liver. Abnormalities of the hepatic parenchyma, edge and periportal fibrosis were statistically more frequent in these patients. The Williams ultrasound score showed high specificity (91.7%; CI 80.9-96.9), but low sensitivity (50%; CI 20.1-79.9) for the diagnosis of liver disease. CONCLUSIONS: The Williams ultrasound score was not a good screening tool when compared to the clinical and biochemical examinations. Since there are currently no adequate tests that can be used to diagnose liver disease, we recommend a sequential evaluation combining clinical, biochemical and ultrasound examinations for the diagnosis of liver disease in CF.

Validação do escore ultra-sonográfico de Williams para o diagnóstico da hepatopatia da fibrose cística / Validation of the Williams ultrasound scoring system for the diagnosis of liver disease in cystic fibrosis

OBJETIVOS: Descrever as alterações hepáticas observadas ao exame ultra-sonográfico de fibrocísticos do Ambulatório de Fibrose Cística do Hospital das Clínicas da UFMG, comparar os achados ultra-sonográficos com critérios clínicos e bioquímicos e validar o escore de Williams para o diagnóstico de hepatopatia associada à fibrose cística. MÉTODOS: Setenta fibrocísticos foram acompanhados prospectivamente e submetidos a exame clínico, bioquímico e ultra-sonográfico. Os achados ultra-sonográficos foram comparados com os resultados do exame clínico e bioquímico. Para a validação do escore ultra-sonográfico de Williams, os critérios clínicos e bioquímicos foram utilizados como padrão-ouro. Foram calculados sensibilidade, especificidade, valor preditivo positivo e valor preditivo negativo do escore de Williams. Para os cálculos, os pacientes foram divididos em dois grupos: normal ao exame ultra-sonográfico (escore = 3) ou alterado (escore > 3). RESULTADOS: Dez pacientes preencheram os critérios clínicos e/ou bioquímicos para hepatopatia (14,3 por cento). Todos os pacientes hepatopatas segundo os critérios clínicos e/ou bioquímicos apresentavam alguma alteração ao exame ultra-sonográfico. As alterações do parênquima hepático, borda hepática e fibrose periportal foram encontradas mais freqüentemente entre os hepatopatas, com diferença estatisticamente significativa. O escore de Williams apresentou alta especificidade (91,7 por cento; IC 80,9-96,9), mas baixa sensibilidade (s = 50 por cento; IC 20,1-79,9) para o diagnóstico da hepatopatia. CONCLUSÕES: O escore de Williams não constituiu um bom exame de triagem quando comparado ao exame clínico e bioquímico. Uma vez que ainda não há nenhum teste que, utilizado isoladamente, apresente sensibilidade adequada, é recomendável a utilização conjunta dos exames clínico, bioquímico e ultra-sonográfico no diagnóstico da hepatopatia associada à fibrose cística, sempre em avaliações seqüenciais.

Triagem diagnóstica da hepatopatia da fibrose cística / Diagnostic screening of liver disease in cystic fibrosis

Objetivo: determinar a prevalência de alterações clínicas e bioquímicas sugestivas de hepatopatia na população de fibrocísticos atendidos no ambulatório de fibrose cística do Hospital das Clínicas da Universidade Federal de Minas Gerais, descrever o grupo de hepatopatas e compará-lo com o de não-hepatopatas, em relação a diversas variáveis clínicas e laboratoriais.Métodos: estudo descritivo, resultante da avaliação prospectiva e, parcialmente, retrospectiva de 106 fibrocísticos. A doença hepática foi definida pela presença de hepatomegalia (>2,5cm da rebordacostal direita) firme, e/ou esplenomegalia, e/ou aumento persistente e significativo (> 1 ,5 vezes o limite superior da normalidade, por pelo menos seis meses) de pelo menos duas das enzimas hepáticas (AST , ALT, GGT e FA).Resultados: hepatomegalia foi verificada em sete pacientes (6,6por cento), e esplenomegalia em cinco (4,7por cento). A atividade da AST mostrou-se alterada em 18,9por cento dos pacientes, AL T em 9,4por cento, GGTem II ,3por cento e F A em 46,2por cento. Elevações significativas e persistentes das enzimas hepáticas ocorreram em nove pacientes (8,5por cento). Dezfibrocísticos (9,4por cento) preencheram os critérios de hepatopatia. Foram excluídas outras causas de doença hepática. A média de idade dos pacientes com alterações sugestivas de hepatopatia foi de 7,7 anos.Houve predominância absoluta do sexo masculino. Todos os pacien-tes permanecem assintomáticos.Conclusões: a prevalência da hepatopatia associada à fibrose cística foi de 9,4por cento. A maior freqüência de elevações transitórias epouco significativas das enzimas hepáticas...

[Diagnostic screening of liver disease in cystic fibrosis]. / Triagem diagnóstica da hepatopatia da fibrose cística.

OBJECTIVE: To determine the prevalence of clinical and biochemical abnormalities suggestive of liver disease in the population of patients with cystic fibrosis (CF) seen at the CF Outpatient Clinic of the Federal University of Minas Gerais; to describe the group of patients with liver disease and to compare it with the group without liver disease, regarding several clinical and laboratory variables. METHODS: Descriptive study, resultant of a prospective, and partially retrospective assessment of 106 patients with CF. Liver disease was defined by the presence of firm hepatomegaly (>2.5 cm from the right costal margin), and/or splenomegaly, and/or persistent and significant increase (>1.5 times the upper limit of normality, over six months) of at least two serum liver enzymes (alanine aminotransferase--ALT, aspartate aminotransferase--AST, alkaline phosphatase--ALP, gamma-glutamyl transpeptidase--GGT). RESULTS: Hepatomegaly was verified in seven patients (6.6%) and splenomegaly in five (4.7%). AST activity was altered in 18.9% of the patients, ALT in 9.4%, GGT in 11.3%, and ALP in 46.2%. Significant and persistent increase in liver enzyme activities was verified in nine patients (8.5%). Ten patients with CF (9.4%) fulfill the criteria for liver disease. Other causes of liver disease were excluded. The mean age of the patients with liver disease was 7.7 years. There was absolute predominance of the male sex. All the patients are without symptoms. CONCLUSIONS: The prevalence of liver disease associated with CF was 9.4%. The frequent and transitory insignificant elevations of liver enzymes are well documented in the literature. Its significance as a predictor of liver disease has not been determined yet. However, the results of this study enhance the need for longitudinal assessment in order to define cases of liver disease in CF.