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

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

Factor V Leiden is not common in children with portal vein thrombosis.

Portal vein thrombosis (PVT) is a rare condition affecting both children and adults, and occurs in association with a wide variety of clinical situations. On the other hand, the development of PVT in patients under these situations indicates that other contributing factors could be involved. Recently a missense mutation in the factor V gene (1691G-->A), known as factor V Leiden, has been identified and results in abnormal factor V product, resistant to proteolytic inactivation by activated protein C and thus predisposes to thrombosis. This study was carried out to verify if children with PVT have an increase in frequency of factor V Leiden. Allele-specific restriction analysis and single strand conformational polymorphism (SSCP) were used to test for factor V Leiden in 20 children with PVT and 64 normal children. None of the PVT children were heterozygous or homozygous for the factor V Leiden, and one control child was heterozygous. This study demonstrates that factor V Leiden is not common in children with PVT, and is not a prerequisite for this thrombotic event.

Gastric emptying in rats with acetaminophen-induced hepatitis.

The objective of this work was to study the gastric emptying (GE) of liquids in fasted and sucrose-fed rats with toxic hepatitis induced by acetaminophen. The GE of three test meals (saline, glucose and mayonnaise) was evaluated in Wistar rats. For each meal, the animals were divided into two groups (N = 24 each). Group I was fed a sucrose diet throughout the experiment (66 h) while group II was fasted. Forty-two hours after the start of the experiment, each group was divided into two subgroups (N = 12 each). Subgroup A received a placebo and subgroup B was given acetaminophen (1 g/kg). Twenty-four hours later, the GE of the three test meals was assessed and blood samples were collected to measure the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and acetaminophen. In group IB, the mean AST and ALT values were 515 and 263 IU/l, respectively, while for group IIB they were 4014 and 2472 IU/l, respectively. The mean serum acetaminophen levels were higher in group IIB (120 micrograms/ml) than in group IB (87 micrograms/ml). The gastric retention values were significantly higher in group IIB than in group IIA for all three test meals: saline, 51 vs 35%; glucose, 52 vs 38% and mayonnaise, 51 vs 29% (median values). The correlation between gastric retention and AST levels was significant (P < 0.05) for group IIB for the three test meals: r = 0.73, 0.67 and 0.68 for saline, glucose and mayonnaise, respectively. We conclude that GE is altered in rats with hepatic lesions induced by acetaminophen, and that these alterations may be related to the liver cell necrosis caused by the drug.

Correlation between the severity of acute hepatic necrosis induced by acetaminophen and serum aminotransferase levels in fasted and sucrose-fed rats.

The relationship between serum aminotransferase levels and the acute hepatic necrosis induced by acetaminophen was studied in 24 male Wistar rats (220-265 g). The animals were divided into two groups, one of which was fasted for 66 h (group I) while the other was fed only sucrose cubes ad libitum (group II). The animals received I g acetaminophen per kg body weight 42 h after the onset of the experiment. Twenty-four hours later, blood was drawn to measure aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and the liver was removed for both macro- and microscopic examination. The intensity of the hepatic necrosis was scored according to the extent of the lesion. The hepatic necrosis was more frequent and intense in group I, with the aminotransferase levels being higher in this group (median AST and ALT levels were 3900 IU/l and 2511 IU/l, respectively, for group I and 119 IU/l and 79 IU/l, respectively, for group II). There was a positive correlation (rs) between the intensity of hepatic necrosis assessed microscopically and the levels of AST (group I, rs = 0.83; group II, rs = 0.79) and ALT (group I, rs = 0.58; group II, rs = 0.80). These findings suggest that aminotransferase levels are a reliable indicator of the degree of hepatic necrosis in this model of acetaminophen intoxication.

Chagasic megaesophagus and megacolon diagnosed in childhood and probably caused by vertical transmission.

Reports on children presenting symptoms compatible with the chronic phase of Chagas disease are sporadic. We report a case of a 7-year-old boy who had megaesophagus and megacolon, both of them a consequence of the trypanosomiasis. The etiology was established by means of laboratory and histological features. Based on epidemiological data, the authors concluded that vertical transmission was the most probable route of acquisition. This diagnosis should be considered in children presenting similar complaints, even those living away from endemic areas.

[Isoniazid-induced hepatic failure. Report of a case]. / Insuficiência hepática pelo uso de isoniazida. Relato de caso.

Isoniazid and pyrazinamide are both well-known hepatotoxic drugs. When isoniazid is used, the hepatic lesion appears before than when pyrazinamide is used. This paper intends to relate a case of a 5-month-old patient who had lungs' and meningeal tuberculosis and who developed toxic hepatitis accomplished by hepatic failure while he was being treated with isoniazid, pyrazinamide and rifampicin. The clinic manifestations and the laboratory alterations were detected in the fifth day of treatment and the recovery was fast; and almost complete by the end of the first week, in which the use of isoniazid had been suspended. Although it was necessary to take the patient to the intensive care unit, he had a good recovery, without sequels.

[The role of the abdominal ultrasonography and percutaneous liver biopsy in the differential diagnosis of neonatal cholestasis]. / Valor da ultra-sonografia abdominal e da biopsia hepática percutânea no diagnóstico diferencial da colestase neonatal.

Neonatal cholestasis still presents a diagnostic challenge, both from the anatomic and etiologic point of view. Distinguishing intrahepatic from extrahepatic causes of cholestasis is of paramount importance since the latter may be treated by surgery but prognosis depends on the age at which operation is performed. Many tests have been proposed to help in differentiating these two entities, among which liver biopsy is the most frequently employed, and ultrasonography one of the most recently included. Our purpose is to present our experience with these two methods in the differential diagnosis of intra and extrahepatic causes of cholestasis. From January 1989 to July 1993, 35 patients with neonatal cholestasis were evaluated through a protocol which included liver biopsy and ultrasonography. The latter was performed after a 4 hour fast and was considered indicative of extrahepatic cholestasis when the gallbladder was not visualized, was hypoplastic or non-functioning, or if a cystic structure was seen at the extrahepatic biliary tree. Sensitivity, specificity, and accuracy were determined for these two tests. Seventeen patients were found to have extrahepatic cholestasis (all with biliary atresia) and 18 intrahepatic cholestasis, on the basis of clinical evolution or operative findings. Sensitivity was 100% for ultrasonography and 76% for liver biopsy in diagnosing extrahepatic cholestasis. Accuracy was 83% for ultrasonography and 86% for biopsy, rising to 96% when both tests were considered together. Based on these findings we strongly recommend ultrasonography with definite criteria as the initial investigation tool in the management of neonatal cholestasis, associated with liver biopsy.

[Pseudo-tumoral schistosomiasis: case report]. / Esquistossomose pseudo-tumoral: relato de um caso.

The schistosomiasis is an endemic disease in Brazil. The most frequent forms are: intestinal, hepatosplenic and hepatointestinal. Rare forms also manifest such as pseudo-tumoral form. The objective of this paper is to report a 8 years-old boy, from Minas Gerais State, with pseudo-tumoral schistosomiasis. He was submitted an exploratory laparotomy and a biopsy from abdominal mass was made. The histologic studies showed a chronic inflammatory process, with a large number of S. mansoni eggs. The treatment was a single-dose of oxaminiquine (20 mg/kg), with a positive evolution, with non-sequel observed after two years of follow-up.

[Portal vein thrombosis in children: clinical and laboratory study of 26 cases]. / Trombose de veia porta em crianças: estudo clínico e laboratorial de 26 casos.

Portal vein thrombosis represents one of the most frequent causes of portal hypertension in childhood. The aim of the present study was to describe the clinical and laboratorial characteristics of portal vein thrombosis in pediatric patient. We studied 26 children with diagnosis of portal vein thrombosis through splenoportography (two patients) and ultrasound scan (24 patients) which ages varied from 2 months to 11 years and 4 months (median-5 years and 3 months). Data of the patient history, physical and laboratories examination were used to a retrospective study which was done through medical record analysis. The main complaint of the examination was hematemesis, which was found in 57.6%. In 26.9% a possible risk factor for portal vein thrombosis was found [catheterization of the umbilical vein (four), sepsis (two), omphalitis (one)]. Splenomegaly was present in all cases and the associated illness to portal vein thrombosis were: hepatoportal sclerosis (three), cytomegalovirus infection (two), blastomycosis (two), virus C (two), virus B (one) and virus A (one). The time between the first bleeding and the examination at University of Campinas Hospital, in Campinas, SP, Brazil, varied from 0.23 months to 54 months with a median of 12 months. Only 11.5% of patients underwent the endoscopy with sclerotherapy before going to University of Campinas Hospital. Aminotransferases' activities were considered normal in 20 patients. We could conclude that: 1. The most frequent initial symptom was hematemesis. 2. The known risk factors for portal vein thrombosis were present in about 1/3 of the cases. 3. Laboratorial exams usually indicated absence of hepatocitic lesions. 4. The efforts towards sending the patient to a reference center were late with a delayed diagnostic and with delayed effective therapeutic conduct. 5. In about 50% of the cases there was PVT associated with other hepatic diseases.

[Liver abscess in childhood: report of 8 cases]. / Abscesso hepático na infância: relato de oito casos.

The authors present eight cases of children with liver abscess diagnosed in the Pediatric Nursery of the "Hospital das Clínicas", State University of Campinas, SP, Brazil, during eight years. Five children were younger than five years. They were four boys and four girls. The symptomatology was inespecific. Staphylococcus aureus was the more frequent etiologic agent and in two cases it was seen Ascaris lumbricoides worm inside the abscess. The findings of ultrasound and computadorized tomography were similar. In most cases, were employed the association of broad spectrum antibiotics and percutaneous draining, and a good clinical outcome was observed in all patients.

[Hepatoportal sclerosis associated with portal vein thrombosis in children: report of 3 cases]. / Esclerose hepatoportal associada à trombose de veia porta em crianças: relato de três casos.

Hepatoportal sclerosis is the term used to name a clinicopathological condition responsible for non-chirrotic portal hypertension. A three cases report of children with hepatoportal sclerosis is presented associated with portal vein thrombosis. The first two patients presented as main complaint upper digestive hemorrhage and the third one was admitted for investigation of hepatosplenomegaly. The ultrasonographic exam revealed alterations indicative of extrahepatic portal vein thrombosis in the three cases. The patients underwent liver biopsy for they had presented altered liver enzymes. The main histological findings were: subintimal sclerosis, portal fibrosis and telangiectases of the intrahepatic venous branches, consistent with the diagnosis of hepatoportal sclerosis. The three patients showed good evolution, being the hemorrhage controlled in the first two cases through esclerotherapy of esophageal varices.

[Esophageal intra-abdominal ultrasonographic in children with gastroesophageal reflux: correlation between endoscopic and histopathologic data]. / Ultra-sonografia do esôfago intra-abdominal em crianças portadoras de refluxo gastroesofágico: correlação com achados endoscópicos e histopatológicos.

Gastroesophageal reflux disease has been very often in children and one of its most critical complications is the peptic esophagitis disease. The diagnosis of peptic esophagitis is obtained based on the endoscopic changes and the histologic features. The pressure reduction of the lower esophageal sphincter is one of the elements of the esophagitis pathogenesis. The pressure is related with the length of the esophageal abdominal segment, which can be measured by ultrasonography. The research presented in this paper aims to relate ultrasonographic measurements of esophageal abdominal segment length with endoscopic changes and with esophageal biopsy obtained from children with gastroesophagel reflux disease. We submitted 16 children with gastroesophagel reflux disease, between 10 and 156 months old (median 63.5 months old), to endoscopy and to esophageal biopsy. We verified the following results from endoscopy and biopsy: six of the 16 patients had endoscopic peptic esophagitis and, in five of these (six patients), the same diagnosis was confirmed by biopsy. Ten of the 16 patients had normal endoscopy, but the biopsy of four of these 10 patients showed histologic changes compatible with esophagitis. We observed no relationship between endoscopy and biopsy, when all degrees of histologic change were used to diagnose esophagitis. However, we found high relationship when the mild histologic changes were considered as only a consequence of the reflux. We verified the following results from ultrasonography: five of the six patients with endoscopic peptic esophagitis and all patients with esophagitis determined by biopsy (excluding those with mild histologic changes) had reduced esophageal abdominal segment length. In conclusion, we have found relationship between endoscopic changes and histologic features in the diagnosis of esophagitis and correlation between the reduced esophageal abdominal segment length and the presence of esophagitis.

Diagnosis of alpha-1-antitrypsin deficiency by DNA analysis of children with liver disease.

BACKGROUND: Alpha-1-antitrypsin deficiency is a genetic disorder which is transmitted in a co-dominant, autosomal form. Alpha-1-antitrypsin deficiency affects mainly the lungs and the liver leading, in the latter case, to neonatal cholestasis, chronic hepatitis or cirrhosis. A precise diagnosis of Alpha-1-antitrypsin deficiency may be obtained by biochemical or molecular analysis. OBJECTIVE: The purpose of this study was to use DNA analysis to examine the presence of an alpha-1-antitrypsin deficiency in 12 children suspected of having this deficiency and who showed laboratory and clinical characteristics of the disease. PATIENTS AND METHODS: Twelve patients, aged 3 months to 19 years, who had serum alpha-1-antitrypsin levels lower than normal and/or had hepatic disease of undefined etiology were studied. The mutant alleles S and Z of the alpha-1-antitrypsin gene were investigated in the 12 children. Alpha-1-antitrypsin gene organization was analyzed by amplification of genome through the polymerase chain reaction and digestion with the restriction enzymes Xmnl (S allele) and Taq-1 (Z allele). RESULTS: Seven of the 12 patients had chronic liver disease of undefined etiology and the other five patients had low serum levels of alpha-1-antitrypsin as well as a diagnosis of neonatal cholestasis and/or chronic liver disease of undefined etiology. Five of the 12 patients were homozygous for the Z allele (ZZ) and two had the S allele with another allele (*S) different from Z. CONCLUSION: These results show that alpha-1-antitrypsin deficiency is relatively frequent in children with chronic hepatic disease of undefined etiology and/or low alpha-1-antitrypsin levels (41.6%). A correct diagnosis is important for effective clinical follow-up and for genetic counseling.

Caroli's disease: 6 case studies.

Caroll's disease is characterized by congenital non-obstructive dilatation of the intrahepatic bile ducts of undefined etiology. It is a rare disease usually affecting the whole liver but it may affect a lobe or a segment (11). This study shows the evolution of 6 cases (2 boys and 4 giris) that were diagnosed with Caroli's disease at a referral service. Their ages ranged from 2 to 16 years--median age 10 years. One of the patients presented with cholangitis, while hepatomegaly was observed in 83% of the cases. Four of the patients presented biliary lithiasis and in one of these cholesterol crystals could be observed in the duodenal secretion. The diagnosis was confirmed in 4 cases by endoscopic retrograde cholangiopancreatography, in 1 by cholangioresonance and 1 by echography. Two of the patients also presented congenital hepatic fibrosis. The outpatient clinic follow-up indicated that all the patients evolved well with the exception of one patient who was selected as a candidate for liver transplantation.

Steroid-induced cataracts in patients with autoimmune hepatitis.

BACKGROUND: Posterior subcapsular cataract (PSC) has been reported in patients on corticosteroids therapy for various pathologies. Autoimmune hepatitis (AIH) is a progressive inflammatory hepatic disease for which corticosteroids are recommended but PSC has not yet been reported in AIH patients on corticosteroids therapy. METHODS: The AIH patients at our service underwent an ophthalmological assessment and their files were analyzed establish the dosage and duration of medication, the presence of visual complaints and the type of AIH, in order to correlate these with the ophthalmological findings. Patients were examined with a slit lamp following pupil dilation. RESULTS: 17 AIH patients evaluated, only one patient had PSC. CONCLUSION: Although the frequency of PSC was low (1/17) in AIH patients on costicosteroid therapy, these individuals should undergo occasional ophthalmological assessment for the presence of cataracts since their visual acuity and quality of life may be adversely affected.

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

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

[Diagnosis, therapy and follow-up of infants with urethral valves, treatment concept in the 1st year of life]. / Diagnostik, Therapie und Verläufe von Säuglingen mit Harnröhrenklappen, Behandlungskonzept im 1. Lebensjahr.

Within the framework of a joint follow-up we report on the treatment of 57 infants with urethral valves (35 babies from Munich and 22 from Siegen) in the first year of life, studied between 1974 and 1986. In 16 newborn the diagnosis and initiation of treatment was effected during the first four weeks of life (Group I) and in 41 babies during the 2nd to 12th month (Group II). In three cases, diagnosis of suspected urethral valve was made prenatally. Primary management and the concept of further treatment are described. Primary therapy is determined by the general condition after birth, presence of urosepsis and the extent of any existing renal insufficiency. 2 children died, both from Risk Group I. 5 children are in a state of compensated renal insufficiency. In 2 newborn we were compelled to perform supravesical urinary drain and in 3 children a suprapubic drain. Secondary nephrectomy became necessary in 4 children, 3 of whom belonged to Risk Group I. In 23 of 57 children valve resection followed by transurethral drainage was the only therapy. In 22 of 57 children corrective surgery was performed subsequently (neo-implantation, with and without modellage, stenosis of the ureter exit). The article reports on the course in each case.

[Choledochal cyst: a 10-year experience] / Cisto de colédoco: experiência de 10 anos.

BACKGROUND: Choledochal cyst is a rare abnormality usually found in infancy and childhood and mainly in females. Outcome depends on early diagnosis, complete resection of the cyst and proper hepaticoenterostomy.OBJECTIVE: The aim of this paper is to evaluate the outcome of 18 patients operated in ten years. METHODS: Retrospective chart review. RESULTS AND DISCUSSION: Age ranged between 20 days and 13 years (mean 3 years). Fifteen (83%) were female and 03 (17%) male. Signs presented included 15 (83%) with jaundice, 11 (61%) with dark urine, 10(55%) with pale colored stools, 09 (50%) with abdominal pain and palpable mass in only 02(11%). Ultrasonography identified the cyst in 14 (77%) patients. Endoscopic retrograde cholangio-pancreatography demonstrated a long common duct in three of four cases. Anatomical types were: 09 type I, 01 type II, 07 type IV and 01 type V. Except for one patient who had a type V cyst, all patients underwent cyst resection plus Roux-en-Y hepaticojejunostomy. There were two (11%) early postoperative deaths related to deterioration of liver function. Thirteen (86%) of the 15 patients available to follow-up were symptom-free without late complications at a mean period of three years, and two (14%) patients developed chronic pancreatitis.

Study of hemostasis in pediatric patients with portal vein thrombosis.

We describe the behavior of hemostatic variables in children with portal vein thrombosis (PVT) and in a control pediatric population. Hereditary protein C (PC) or protein S (PS) deficiency was not a etiologic factor for PVT in children. Minor signs of consumption of coagulation factors II, V, fibrinogen and hyperfibrinolysis were detected. One child had lupus anticoagulant (LA).