Factors predictive of an obstructive pathology among Filipino infants with neonatal cholestasis

@#<p style="text-align: justify;"><strong>Objective.</strong> To determine factors predictive of obstructive neonatal cholestasis among Filipino infants and to describe their outcome.</p><p style="text-align: justify;"><strong>Methods.</strong> Jaundiced infants within the first eight weeks of life with liver biopsy were included. Excluded were cholestasis secondary to metabolic or infective causes. Retrospective chart review (2009-2012) and prospective recruitment of patients (2013) were done. A final diagnosis of non-obstructive or obstructive neonatal cholestasis was made on clinical, biochemical, ultrasonographic, and histologic findings, using histology and/or operative cholangiogram as the gold standard. The outcome was assessed on the 6th and 12th months from diagnosis. The crude odds ratio for obstructive jaundice was computed. Multiple logistic regression on significant variables (p-value <0.05) was done.</p><p style="text-align: justify;"><strong>Results.</strong> Two hundred sixty-three (263) patients were included: 161 with non-obstructive and 102 with obstructive cause. Mean age at first consult was higher in those with obstruction. On logistic regression, females (OR:2.3), absence of a family history of idiopathic neonatal hepatitis (OR:4), and persistently pale/acholic stools (OR:13) were predictive of obstruction. 85% of patients with a non-obstructive cause are alive and well, while 80% of patients with obstruction have died.</p><p style="text-align: justify;"><strong>Conclusion.</strong> Among jaundiced infants females, the absence of a family history of idiopathic neonatal hepatitis and persistently pale yellow/acholic stools were predictive of obstruction. The outcome was poor in patients with obstructive jaundice.</p>

Mevalonate Kinase Deficiency as Cause of Periodic Fever in Two Siblings

Mevalonate kinase deficiency (MKD) is a rare autosomalrecessive autoinflammatory disease caused by mutations inMVK. We report two siblings with MKD, presenting withrecurrent febrile illnesses, detected to have compoundheterozygous variants in MVK. MKD mimics common pediatricconditions and should be considered as a differential diagnosis.

GC/MS based metabonomie study of neonatal hepatitis syndrome / 国际儿科学杂志

Objective Early detection is the most effective way to improve the clinical outcome of biliary atresia(BA).Emerging metabolomics provides a powerful platform for discovering novel biomarkers and biochemical pathways to improve early diagnosis.The aim of this study is to find the potential biomarkers to distinguish BA from neonatal hepatitis syndrome(NHS) by using a metabolomics method.Methods We comprehensively analyzed the serum metabolites in a total of 26 blood samples from patients with BA or neonatal hepatitis syndrome(NHS) and from normal individuals using advanced metabolomic approaches.Results The levels of propanoic acid,hexadecanoic acid,eicosanoic acid,octadecenoic acid and cholesterol significantly increased in the BA group.Conclusion The levels of L-Tyrosine(Tyr)were reduced in the BA group compared to those in the NHS group,but still higher than the normal controls.The levels of L-Proline(Pro) in the NHS group were significantly elevated compared to those in the BA group.And at the same time,we find 5 patients with cirin deficiency.This study demonstrates the possibility of metabolomics as non-invasive biomarkers for the early detection of BA and also provides new insight into pathophysiologic mechanisms for BA.

Comparison of hepatobiliary injury for newborn BALB/c mice which induced by different titers of rhesus rotavirus / 中华实验和临床病毒学杂志

Objective@#To compare the hepatobiliary injury difference of newborn BALB/c mice infected by different titers of rhesus rotavirus(RRV).@*Methods@#Neonatal mice(n=80) were randomly separated into 4 groups and were intraperitoneally inoculated with different titers of rotavirus: High titer group(1×107 PFU/ml); Medium titer group(1×106 PFU/ml); Low titer group(2.5×105 PFU/ml); Control group (only culture medium) within the first 24 hours after birth. All mice were sacrificed at day 12 after RRV inoculation then the liver and blood samples were collected. Meanwhile, mice were observed daily for at least 12 days, including their weight, skin color and survival situation. Liver functions were examined by serum biochemical test and morphologic changes in the biliary tract were observed. Tissue sections underwent H&E staining and immunohistochemically analysis for the presence of CK19.@*Results@#Compared with the normal mice, the mice in the experimental group had different degrees of skin jaundice, weight lost, survival rate decreased, liver function damage. In the experimental group, the symptom of low titer group was light, and could be restored to normal, however, when compared with the low titer group, the mice in the high titer group were serious, their skin jaundice was more obvious, weight was significantly reduced and irreversible, survival rate was lower(50%), liver function of TBIL, DBIL, TBA, ALT, ALP were significantly increased.Further analysis showed that the high titer group had high bile duct obstruction rate (80%), with no case of obstruction in the low titer group. Histologic analysis also showed intrahepatic bile duct atresia in the high titer group, a large number of inflammatory cell infiltrated around the portal area, while the morphology of intrahepatic bile duct was almost normal and just a small amount of inflammatory cell infiltrated around the portal area in the low titer group.@*Conclusions@#Different titers of rotavirus had different effects on the newborn mice hepatobiliary system: high titer was easy to cause biliary atresia, and low titer caused hepatitis.

Research progress ofα1-antitrypsin deficiency of mutant Z / 上海交通大学学报（医学版）

α1-Antitrypsin (α1-AT) belongs to serine protease inhibitor (Serpin) superfamily and is the main protease inhibitor in human circulation. It can inhibit many proteases to protect tissues from digradation. The mutant Z (Glu342Lys) of α1-AT predisposes to the early onset of emphysema due to decreased functional α1-AT in the lung and to neonatal hepatitis due to accumulation of α1-AT polymers in the endoplasmic reticulum of hepatocytes, which disrupts the balance between protease and protease inhibitors. This paper reviews recent research progress on the pathogenic mechanism and the prognosis of α1-antitrypsin deficiency.

CD14/-159 and TNFα/-308 promoter polymorphisms are not associated with Development of Idiopathic Neonatal Hepatitis among Filipinos

Objective@# To determine if the CD14/-159 and the TNFα/-308 single nucleotide polymorphisms (SNPs) are associated with the development of Idiopathic Neonatal Hepatitis (INH) in Filipino children. @*Methods@#Genomic DNA from 33 patients diagnosed with INH and 33 age- and sex-matched controls, children without any liver disease, were recruited. Baseline serum total bilirubin (TB), direct bilirubin (DB), and alkaline phosphatase (ALP) of the patients were obtained from their medical records. Genotypes for CD14/159 and TNFα/-308 were determined via PCR and direct sequencing. @*Results@#No significant difference was seen between the frequency of the CD14/-159 T allele (p=0.86) nor the TNFα/-308 A allele (p=0.62) between INH patients and controls. There was also no significant difference between the genotypic distribution of the INH and control populations for both CD14/-159 (p=0.54) and TNFα/-308 (p=0.62). There were also no significant differences noted between the different genotypes of CD14/159 and TNFα/-308 and levels of alkaline phosphatase (p=0.65, p=0.91), total bilirubin (p=0.89, p=0.75), and direct bilirubin (p=0.93, p=0.68). @*Conclusion@#In this preliminary study, CD14/-159 and TNFα/-308 showed no association with the development of INH among Filipinos.

Experiencia de 21años en biopsias hepáticas en el Hospital del Niño Dr. José Renán Esquivel Panamá, 1994-2004

Introducción: La biopsia hepática permite conocer el tipo y extensión de las alteraciones histopatológicas, para ofrecer un diagnóstico especí co en relación con la clínica y hallazgos paraclínicos correspondientes. Material y métodos: Se revisaron retrospectivamente los diagnósticos de las biopsias hepáticas, realizadas durante el periodo del 1 de enero de 1994 hasta el 31 de diciembre del 2014, en los libros de registro del departamento de patología del Hospital del Niño Doctor José Renán Esquivel y se describe la frecuencia de utilización de la técnica abierta versus la técnica percutánea y las patologías encontradas. Resultados: Se realizaron en total 486 biopsias de hígado, de las cuales 88.4% correspondían a biopsias percutáneas, y el 11.6% abiertas. Los diagnósticos más frecuentes encontrados fueron hepatitis neonatal 15%, atresia de vías biliares 12.7%, y cirrosis hepática 8.4%, el resto de los pacientes presentaron distintas patologías. Conclusiones: Este procedimiento ha sido útil en nuestro medio para el diagnóstico y seguimiento de las hepatopatías más frecuentes de la población pediátrica.

Introduction: Liver biopsy can determine the type and extent of histopathological changes, to o er a speci c diagnosis in relation to relevant clinical and paraclinical ndings. Material and methods: We retrospectively reviewed the diagnoses of liver biopsies performed during the period January 1, 1994 until December 31, 2014, in the record books biopsy pathology department at Children's Hospital Doctor Jose Renan Esquivel and frequency of use of open biopsy versus percutaneous and pathologies encountered are described. Results: 486 were conducted in total liver biopsies, of which 88.4% were percutaneous biopsies, and 11.6% open. The most frequent diagnoses found 15% were neonatal hepatitis, biliary atresia 12.7% and 8.4% hepatic cirrhosis; the remaining patients had various diseases. Conclusions: This procedure has been useful in our environment for the diagnosis and monitoring of the most common liver disease in the pediatric population

Histological pattern and outcome of Filipino children with liver disease who underwent percutaneous liver biopsy: A five year survey

BACKGROUND: Histological assessment is important in evaluating liver disease. We determined the clinical diagnose and predominant histological patterns of children with liver disease and association of histological pattern with outcome. METHODS: Consecutive patients RESULT: 470 cases (1month-18years; 65% males; 85% CONCLUSION: Most common clinical diagnoses were neonatal hepatitis and biliary atresia. Predominant histological patterns were giant cell and obstructive type. Histological patterns of giant cell hepatitis seen in neonatal hepatitis resulted in better outcome.

Colestasis neonatal e infantil: Aproximación al diagnóstico histopatológico / Neonatal and Infantile Cholestasis: An Approach to Histopathological Diagnosis

Aun cuando el papel de la biopsia hepática está cambiando con el desarrollo de nuevos métodos de diagnóstico y del avance de las técnicas de imagen, de biomarcadores no invasivos, estudios proteómicos y genómicos, la biopsia hepática realizada en el momento y con la indicación adecuadas continúa siendo una importante herramienta para la evaluación y diagnóstico de los niños con colestasis tanto en el periodo neonatal como durante la infancia temprana o tardía, no solo para determinar una etiología o establecer un pronóstico sino para guiar una terapia (1). Son múltiples las causas y varios los patrones morfológicos observados, puede estar relacionada a un defecto genético del metabolismo hepático incluyendo la síntesis de ácidos biliares, la formación y función de transportadores de membrana o a alteraciones en el desarrollo de las vías biliares, muchos de los cuales pueden sobreponerse y deben interpretarse en conjunto con los hallazgos clínicos, genéticos y de laboratorio. Los síndromes heredados que producen colestasis intrahepática y la atresia biliar son las causas más comunes de enfermedad hepática crónica y la indicación principal para el trasplante hepático en niños. El enfoque que aquí daremos hace hincapié en la estrecha colaboración que debe existir entre pediatras, gastroenterólogos, cirujanos pediátricos y los patólogos para la correcta identificación y posterior manejo sea médico o quirúrgico incluyendo el trasplante hepático, de muchas de las patologías colestásicas que afectan este grupo etario (2, 3).

Although the role of liver biopsies is changing with the development of new diagnostic methods and advances in imaging techniques, non-invasive biomarkers, proteomic and genomic studies, a liver biopsy performed at the right time and with appropriate indications continues to be an important tool for assessment and diagnosis of children with cholestasis. This is equally true in the neonatal period, in early childhood, and in late childhood not only for determination of an etiology and establishing a prognosis, but also for guiding treatment of the patient (1). There are multiple causes and morphological patterns that may be related to a genetic defect in aspects of hepatic metabolism including synthesis of bile acids, formation and function of membrane transporters, and alterations in the development of the bile ducts. Many of these may overlap and should be interpreted in conjunction with clinical, genetic and laboratory findings. Inherited syndromes that produce intrahepatic cholestasis and biliary atresia are the most common causes of chronic liver disease and the leading indication for liver transplantation in children. The approach we present here emphasizes the close cooperation that should exist between pediatricians, gastroenterologists, pediatric surgeons and pathologists for proper identification of many of the cholestatic diseases that can affect this age group. Subsequent surgical or medical management may include liver transplantation (2, 3).

Utility of Tc99m-Mebrofenin hepato-biliary scintigraphy (HIDA scan) for the diagnosis of biliary atresia.

Aim: To determine the utility of Tc99m-Mebrofenin hepato-biliary scintigraphy (HIDA scan) for diagnosis of biliary atresia in patients with neonatal cholestasis. Methods: Our study involves the retrospective analysis of 46 patients with neonatal cholestasis who underwent HIDA scans at the Pediatric Hepatobiliary Clinic, BJ Wadia Hospital for Children from May 2005 to July 2007. Biliary atresia (BA) was diagnosed on the basis of intra-operative cholangiogram. Non-BA patients were included in the neonatal hepatitis (NH) group. All patients received phenobarbitone and ursodeoxycholic acid for 5 days, prior to the HIDA scan. The HIDA scan was evaluated on the basis of uptake of the radioactive tracer by the liver at 5 minutes after intravenous injection; retention of radioactive tracer within the liver at 24 hours after injection and visualization of excretion of tracer into the intestine upto 24 hours after administration. The results of the HIDA scans were analyzed and correlated with the final diagnosis, gender and age of the patients. Chi-square test was employed for statistical analysis. Results: The age of presentation of our patients ranged from 5 days to 6 months. The male: female ratio was 37:9. Of the total 46 patients, 28 had BA and 18 had NH. All 28 (100%) patients diagnosed with BA showed persistent radiotracer in the liver at 24 hours whereas 17 (94.4%) of the 18 NH patients showed hepatic radiotracer retention (p=0.207), the difference being statistically insignificant. Twenty two (78.6%) patients of BA showed no excretion of the radiotracer at 24 hours whereas only 7 (38.9%) of the NH group did not excrete the radiotracer (p=0.007), which was statistically significant. Neither the sex nor the age of the child contributed to any difference on the hepatic retention (p=0.618 and 0.235, respectively) or on the intestinal excretion (p=0.307 and 0.9, respectively) of the radiotracer. Conclusion: HIDA scan is a useful tool for screening of biliary atresia in patients with neonatal cholestasis. Non excretion of the radioactive radiotracer into the intestines even after 24 hours of radiotracer administration can suggest biliary atresia in majority of patients.

Comportamiento de la colestasis del recién nacido y del lactante en el Hospital Pediátrico William Soler / Behavior of newborn and infant cholestasis in the William Soler Children Hospital

INTRODUCCIÓN. Los recién nacidos y lactantes pequeños tienen una inmadurez funcional y anatómica que justifica que las enfermedades hepáticas que se manifiestan en estas edades tengan a la ictericia como signo principal. La lista de procesos que causan colestasis en este período es muy extensa e incluye anomalías estructurales, extrahepáticas e intrahepáticas, y procesos que alteran los mecanismos de síntesis y excreción de las sales biliares. El objetivo del estudio fue describir el comportamiento de los casos de colestasis del lactante atendidos en el Servicio de Hepatología del Hospital Pediátrico William Soler, evaluados de forma protocolizada entre enero del 2004 y diciembre del 2006. MÉTODOS. Se realizó un estudio descriptivo y retrospectivo. La muestra estuvo constituida por 76 lactantes con diagnóstico de colestasis, que fueron evaluados de forma protocolizada en el período referido. Se analizaron las variables sexo, edad gestacional y peso al nacer, antecedentes peri y posnatales, presencia o ausencia de signos de insuficiencia hepática, así como localización regional y causas de la colestasis. Se elaboró una base de datos en SPSS (versión 12) y las variables fueron analizadas de forma porcentual. RESULTADOS. Se encontró predominio de recién nacidos del sexo masculino (45; 59,2 por ciento), a término (63; 82,9 por ciento), de peso normal (50; 65,7 por ciento) y sin antecedentes peri y posnatales. Solo en el 9,2 por ciento de los casos la colestasis se asoció a insuficiencia hepática. La frecuencia de colestasis intrahepática y extrahepática fue similar. Las principales causas de colestasis encontradas fueron atresia de las vías biliares (24; 31,5 por ciento), hepatitis neonatal idiopática (15; 19,8 por ciento), infección por citomegalovirus (14; 18,5 por ciento) y síndrome de espesamiento de la bilis (9; 11,9 por ciento). CONCLUSIONES. El comportamiento de las diferentes causas de colestasis es heterogéneo…

INTRODUCTION. The small newborns and infants have a functional and anatomical immaturity justifying that the liver diseases present in these ages have the jaundice as the main sign. The list of processes causing cholestasis during this period is very large including structural, extrahepatic, intrahepatic anomalies and also processes altering the mechanisms synthesis and the excretion of bile salts. The aim of present study was to describe the behavior of the cases of infants presenting with cholestasis seen in the Hepatology Service of the William Soler Children General Hospital, assessed in a programmed way between January, 2004 and December, 2006. METHODS. A retrospective and descriptive study was conducted. Sample included 76 patients diagnosed with cholestasis, assessed in a programmed way during this period. Variables analyzed were: sex, gestational age and birth weight, perinatal and postnatal backgrounds, presence or absence of cholestasis. A database was designed in SPSS (version 12) and the variables were analyzed in percentage way. RESULTS. There was predominance of male newborns (45, 59,2 percent), term (63, 82,9 percent) of normal weight (50,65,7 percent) and without perinatal and postnatal backgrounds. Only in the 9,2 percent of cases the cholestasis was associated with a liver failure. Frequency of intrahepatic and extrahepatic cholestasis was similar. The major causes of cholestasis present were: biliary tracts atresia (24, 31,5 percent), idiopathic neonatal hepatitis(15, 19,8 percent), cytomegalovirus infection (14, 18,5 percent) and bile thickening (9,11,9 percent). CONCLUSIONS. Behavior of different causes of cholestasis is heterogeneous and the differences as regards the frequencies of cholestasis causes is in some extent a reflection of the differences in the composition of the group of series

Colestasis del recién nacido y del lactante / Cholestasis of newborn and infant

Los recién nacidos y lactantes pequeños tienen una inmadurez funcional y anatómica que justifica que las enfermedades hepáticas que se manifiestan en estas edades tengan la ictericia como signo principal y que otros procesos extrahepáticos o sistémicos puedan condicionar colestasis. La colestasis del lactante es un síndrome clínico caracterizado por ictericia, acolia o hipocolia, y coluria, que evoluciona con elevación de la bilirrubina directa y de los ácidos biliares séricos. La evaluación diagnóstica del lactante con colestasis, realizada por un equipo multidisciplinario, debe minimizar la realización de pruebas innecesarias para lograr un diagnóstico correcto en el menor tiempo posible, diferenciar entre colestasis intrahepática o extrahepática y lograr un diagnóstico etiológico, que incluya aquellos procesos que ponen en peligro la vida o requieren un tratamiento específico médico o quirúrgico. El presente trabajo pretende revisar las principales causas, procedimientos diagnósticos y el enfoque terapéutico de la colestasis del recién nacido y del lactante en aras de contribuir a su diagnóstico temprano y su tratamiento adecuado

The small newborns and infants have a functional anatomical immaturity justifying that liver diseases present at these ages have the jaundice as leading sign and that other extra-hepatic or systemic processes may conditioning the Cholestasis. Infant Cholestasis is a clinical syndrome characterized by jaundice, acholia or hypoacholia and choluria evolving with a rise of direct bilirubin and of serum biliary acids. The diagnostic assessment of infant presenting with Cholestasis made by a multidisciplinary staff must to minimize the carrying out of unnecessary tests to obtain an appropriate diagnosis in less time, to differentiate among the intrahepatic or extrahepatic cholestasis and to achieve an etiologic diagnosis including the processes threatening the life or that requiring a medical or surgical specific treatment. The aim of present paper is to review the leading causes, diagnostic procedures and the therapeutical approach of cholestasis en the newborn and in the infant to contribute to its early diagnosis and its appropriate treatment

Evaluation of ultrastructural changes by electron microscopy in neonatal cholestasis.

Background: Biliary atresia (BA) and idiopathic neonatal hepatitis (NH) account for 50-70% of all cases with neonatal cholestasis. The treatment of the former is early surgical intervention, while the latter requires non-surgical supportive care. Failure to differentiate the two conditions may result in avoidable surgery in NH, which may significantly increase morbidity. The lack of differentiating clinical features, biochemical markers and other specific investigations to distinguish the two is still a major problem. Aim: This study was thus initiated to evaluate electron microscopic changes in the liver in patients with NH and BA, to correlate these with changes on light microscopy and look for specific differentiating features between the two. Methods: Ten patients with neonatal cholestasis whose liver specimens were available for electron microscopic analysis were included in the study. There were 6 patients with BA and 4 patients with NH. Results: Among the biochemical parameters, serum alkaline phosphatase and gamma glutamyl transpeptidase were significantly higher in BA than in patients with NH. On light microscopy, giant cell transformation was seen in 75% patients with NH and 33.3% of patients with BA. Even in BA, intracellular cholestasis was more prominent than ductular cholestasis (100% vs. 50%). Ductular proliferation was seen in 50% of NH patients and all patients of BA. Electron microscopy revealed prominent endoplasmic changes in all patients with NH and to a milder degree in BA. Changes in mitochondria and glycogen content were similar in both groups. Conclusion: Ultrastructural changes in neonatal cholestasis seen through electron microscopy are largely non-specific and do not differentiate BA from NH.

The Clinical Features of Chronic Neonatal Hepatitis: Non-familial, Non-metabolic and Non-A, B, C Viral Hepatitis / 대한소아소화기영양학회지

PURPOSE: Neonatal hepatitis is the major cause of neonatal cholestasis and may be divided into infectious, metabolic, genetic, and idiopathic neonatal hepatitis. Non-familial, non-metabolic, and non-A, B, C viral neonatal hepatitis is known to have made satisfactory progress, but little is known about its chronic clinical features. METHODS: Clinical and histological assessments were carried out in 34 cases with chronic neonatal hepatitis [elevated serum alanine aminotrasferase (ALT) level for more than 6 months] except for A, B, C viral hepatitis, metabolic, or genetic neonatal hepatitis, who were admitted to the Department of Pediatrics, Pusan National University Hospital, from January 1998 to January 2004. RESULTS: Males were more common (70%). Jaundice (100%) and hepatomegaly (44%) were frequent manifestations. Peak serum ALT levels were most commonly below 300 IU/L in 41.2% of patients and peak serum direct bilirubin levels were most commonly between 1.0~5.0 mg/dL in 50% of patients. Ten cases (34%) of 29 patients had positive serum cytomegalovirus (CMV) IgM or urine CMV polymerase chain reaction. Serum ALT level was normalized within 1 year in 11 (37.9%) of 29 cases, and within 2 years in 9 (69.2%) of 13 cases. Serum ALT level was elevated persistently over 2 years in four (30.7%) of 13 cases. Histologic findings such as portal or periportal activity, lobular necrosis, portal or periportal fibrosis were more severe in patients with persistent ALT elevation over 2 years than in those showing normalization of ALT within 2 years (p>0.05). CONCLUSION: When the elevation of ALT level sustains over 1 year in non-familiar, non-metabolic, non-A, B, C viral neonatal hepatitis, an assessment of the severity of liver injury and a careful monitoring about chronic liver disease may be required.

Diagnostic Laparoscopy in Infantile Cholestatic Jaundice

When jaundice persists for more than 14 days postnatally, the early diagnosis of surgical jaundice is important for the prognosis in extrahepatic biliary atresia after draining procedure. The role of diagnostic laparoscopy to differenctiate medical causes of jaundice from biliary atresia is evaluated in this report. Four patients with prolonged jaundice have been included in this study. When the gallbladder was not visualized we proceeded to laparotomy. In patients with enlarged gallbladder visualized at laparoscopy, laparoscopic guided cholangiogram was performed, and laparoscopic liver biopsy was done for those who had a patent biliary tree. Two patients had small atretic gallbladder and underwent a Kasai hepato-portoenterostomy. One patients showed a patent gallbladder and common bile duct with atresia of the common hepatic and intrahepatic ducts, and they underwent a Kasai hepatic-portoenterostomy. One patient showed an enlarged gallbladder and laparoscopic-guided cholangiogram were normal. Laparoscopic liver biopsy was performed. There were no complications. Laparoscopy wth laparoscopic-guided cholangiogram may be a valuable method in accurate and earlier diagnosis in an infant with prolonged jaundice.

The Correlation between Acholic Stool and the Result of Tc(99m) DISIDA Hepatobiliary Scintigraphy and Biochemical Test in Neonatal Cholestasis / 대한소아소화기영양학회지

PURPOSE: The most common causes of neonatal cholestasis are neonatal hepatitis (NH) and extrahepatic biliary atresia (EHBA). Since neonatal cholestasis presents with variable expression of same pathologic process and has similar clinical, biochemical, and histologic features between EHBA and idiopathic neonatal hepatitis (NH), differential diagnosis is often difficult. We reviewed the differences of clinical characteristics and laboratory data to find out any correlation between the results of Tc(99m) DISIDA scan and presence of acholic stool. METHODS: Between June 1993 and January 2001, total 29 infants younger than 4 month-old underwent Tc(99m) DISIDA scan. Their biochemical tests and clinical course were reviewed retrospectively. RESULTS: Patients who had negative intestinal activity on Tc(99m) DISIDA scan showed acholic stool and revealed higher serum direct bilirubin and urine bilirubin level. 18.2% of patients with acholic stool showed intestinal activity on Tc(99m) DISIDA scan and 81.8% of them did not. All the patients without acholic stool showed positive intestinal activity on Tc(99m) DISIDA scan. The result of Tc(99m) DISIDA scan and the presence of acholic stool showed high negative correlation (r :-0.858). Patients with acholic stool and negative intestinal activity on Tc(99m) DISIDA scan showed higher serum total bilirubin level. Patients without acholic stool and positive intestinal activity on Tc(99m) DISIDA scan showed higher serum level of ALT. CONCLUSION: Patients with acholic stool and negative intestinal activity showed high correlation, but 18.2% of patients with acholic stool showed positive intestinal activity. So operative cholangiogram or transcutaneous liver biopsy should be performed for confirmation.

Clinical Course of Transferred patients for Operation Under the Impression of Biliary Atresia

Biliary atresia (BA) is very difficult to distinguish from neonatal hepatitis (NH) and its prognosis depends on the age at the time of Kasai operation. Therefore early differentiation between these two conditions is very important. Although various clinical and laboratory tests have been reported to differentiate between them, they are still of limited value. From 1980 to 1999, forty-five infants were referred to our pediatric surgical unit for operation for suspected BA. Eight patients underwent Kasai operation immediately because late diagnosis. These were excluded from the study. The clinical history, physical findings, radiologic and laboratory examinations of 37 cases were analyzed retrospectively. The average age of BA (n=20) was 55.1+/-6.7 days, and that of NH (n=17) was 55.8+/-5.6 days. The sex ratio of BA was 13:7, and that of NH was 14:3. All the patients had obstructive jaundice and acholic stool except 4 BA and 6 NH patients. Acholic stool with yellow component was more frequent in NH. Onset of jaundice was within 2 weeks after birth in 85% of BA, and in 65% of NH. The onset of acholic stool was within 2 weeks after birth in 60% of BA, and in 23.5% of NH. The duration of jaundice and acholic stool of BA were 50.9+/-6.6 days and 41.3+/-8.4 days and those of NH were 40.1+/-3.1 days and 26.6+/-5.4 days respectively. The ultrasonogram and hepatobiliary scan were useful, but not a definitively reliable method for the differentiation of these two diseases. There was no difference in laboratory data. Seventeen cases had NH among 45 referred cases for Kasai operation with the clinical impression of BA, and 4 cases of 17 NH cases needed to be explored to rule out BA. In conclusion, false positive rate of clinical impression of BA was 37.8%, and negative exploration rate was 8.9%. Therefore, careful clinical observation for 1-2 weeks by an experienced pediatric surgeon was very important to avoid unnecessary operation to rule out NH up to the age of 8 - 10 weeks, so long as the stool had yellow component.

Clinical trial comparing the efficacy of ursodeoxycholic acid and cholestyramine on idiopathic neonatal hepatitis.

common cause of neonatal cholestasis is idiopathic neonatal hepatitis. Several agents have been proposed to counteract the effects of accumulated toxic bile acid such as phenobarbital and cholestyramine. Ursodexycholic acid ( UDCA) is a choleretic agent used in chronic intrahepatic cholestasis. The aim of this study is to compare the efficacy of ursodeoxycholic acid and cholestyramine on hepatic function in idiopathic neonatal hepatitis. Twenty patients were enrolled in this study. The patients were randomized to receive UDCA or cholestyramine orally. There were ten patients in each group. The doses of UDCA and cholestyramine were 15 mg/ kg / day and 350 mg / kg/ day respectively. The duration of the study was 8 weeks. Conventional liver function tests were done initially and at 1,2,4, and 8 weeks. Any side effects of these medications were noted. The ursodeoxycholic acid group showed a significant improvement in levels of total bilirubin, direct bilirubin, and alkaline phosphatase ( P< 0.05). The cholestyramine group showed a significant improvement in levels of total bilirubin, and direct bilirubin ( P< 0.05). There was no significant difference on liver function tests between the groups at any time ( P> 0.05). No side effects were observed. The results showed that both drugs improved cholestasis resulting from idiopathic neonatal hepatitis. The results of this study suggest that UDCA would be an alternative choleretic agent in treatment of idiopathic neonatal hepatitis.

Neonatal "giant cell" hepatitis (with a report of two cases)

We have presented two cases of giant cell hepatitis from the Santo Tomas University Hospital Charity Service which have occurred within a ten-year period (1953-1962), and have compared the incidence of this condition experienced locally to other series reported from abroad. A brief review of the literature is presentedThe summary of the clinical and pathologic aspects is also given. The differential diagnosis between neonatal hepatitis and biliary atresia is often difficult to make even when liver biopsy is performed because the histologic picture is similar in both conditions. The recommended diagnostic procedures include an open liver biopsy followed by cholangiographyPresently the concensus is that giant cell reaction of the liver is a non-specific phenomenon, probably representing a response to diffuse injury of the fetal and neonatal liver. Therefore, this condition is a morphologic or pathologic entity rather than a clinical oneSince the etiology and pathogenesis of giant-cell hepatitis is still poorly understood, the therapeutic measures remain symptomatic and often unsatisfactory. (Summary and Conclusion)

Clinical and Pathological Comparison of Neonatal Hepatitis and Extrahepatic Biliary Atresia in Korean Children

PURPOSE: Neonatal hepatitis and congenital extrahepatic biliary atresia are two major causes of neonatal cholestasis. But the method of therapeutic trials used for each disease is essentially different. Nonetheless, it is very difficult to differentiate these diseases clinically and histologically. This study is aimed to find out major differences between the two by clinical characteristics and scoring of various histological parameters. METHODS: Clinical and histologically assessments were carried out in 8 cases with neonatal hepatitis and 11 cases with extrahepatic biliary atresia, who were admitted to the Department of Pediatrics, Pusan National University Hospital, from January 1991 to June 1997. RESULTS: By sex distribution, males were more commonly had neonatal hepatitis but females were more commonly had biliary atresia. Hepatosplenomegaly and acholic stool were more frequent in biliary atresia.. Serial determinations of serum bilirubin concentrations showed that a steady fall occured in neonatal hepatitis whereas, progressive increase or stability of bilirubin level was noted in biliary atresia. Serum direct bilirubin level of more than 4mg/dL was found more frequently in biliary atresia. Serum aspartate aminotransferase level above 400IU/L was found more frequently in biliary atresia. Bile duct proliferation was more frequent in biliary atresia but Kupffer cell proliferation was more frequent in neonatal hepatitis. There was a significant difference in the total score in the liver biopsy scoring system between the two diseases. CONCLUSION: Females with hepatosplenomegaly and acholic stool, serum direct bilirubin level higher than 4mg/dL, serum aspartate aminotransferase level above 400IU/L, prominent bile duct proliferation and a higher total pathological score in biopsy specimen was found more frequently in biliary atresia.