Eleonora Druve Tavares Fagundes

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.

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 κ 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.

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

OBJETIVO: Apresentar uma revisao atualizada de trombose de veia porta na infância e adolescencia, enfatizando o diagnostico, suas complicacoes e tratamento. FONTE DOS DADOS: Foi realizada revisao da literatura, dos ultimos 10 anos, atraves de pesquisa bibliografica na Internet nos principais sites de busca medica, como o PubMed e MEDLINE, com enfoque na doenca trombose de veia porta e suas repercussoes clinicas. As principais palavras-chave e expressoes pesquisadas foram: portal vein thrombosis, extra-hepatic portal vein obstruction, prognosis, children, portal hypertension, esophagogastric varices. Alem disso, foram consultados os artigos citados nas referencias dos trabalhos selecionados na pesquisa inicial e dos livros textos. SINTESE DOS DADOS: A trombose de veia porta e uma das causas mais comuns de hipertensao porta na infância. A apresentacao clinica inicial pode ser atraves de episodios de hemorragia digestiva ou da presenca de esplenomegalia em exame clinico de rotina. As principais complicacoes sao a hemorragia digestiva, hiperesplenismo secundario a esplenomegalia, retardo de crescimento e biliopatia portal. O diagnostico e realizado atraves da ultra-sonografia abdominal com Doppler. O tratamento e direcionado para as complicacoes, incluindo profilaxia primaria e secundaria de hemorragia digestiva, consequente a ruptura de varizes esofagicas, e derivacoes porto-sistemicas, em casos selecionados. CONCLUSOES:A trombose de veia porta e uma das causas mais importantes de hemorragia digestiva em criancas. Esses episodios acarretam impacto importante na qualidade de vida dos pacientes acometidos. Dessa forma, uma abordagem diagnostica e terapeutica adequada e desejavel na tentativa de se reduzir a morbimortalidade.

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

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%,

Autoimmune hepatitis in childhood: The role of genetic and immune factors

Autoimmune hepatitis (AIH) is a rare chronic inflammatory disease of the liver, which affects a group of patients who lost their immunological tolerance to antigens of the liver. It is clinically characterized by hypergammaglobulinemia, elevated liver enzymes, presence of autoantibodies and histological changes. Although being rare in children, it represents a serious cause of chronic hepatic disease that can lead to cirrhosis and hepatic failure. Clinical findings, exclusion of more common liver disorders and the detection of antibodies antinuclear antibodies, smooth muscle antibodies and anti-LKM1 are usually enough for diagnosis on clinical practice. The pathogenic mechanisms that lead to AIH remain obscure, but some research findings suggest the participation of immunologic and genetic factors. It is not yet knew the triggering factor or factors that stimulate inflammatory response. Several mechanisms proposed partially explain the immunologic findings of AIH. The knowledge of immune factors evolved might result in better markers of prognosis and response to treatment. In this review, we aim to evaluate the findings of research about genetic and immune markers and their perspectives of application in clinical practice especially in pediatric population.

Validation of the Williams ultrasound scoring system for the diagnosis of liver disease in cystic fibrosis

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.

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.

Diagnostic screening of liver disease in cystic fibrosis

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, -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.