Diagnosis Of Neonatal Cholestasis Research Articles

Pathologic approach to Neonatal cholestasis with a simple scoring system for biliary atresia

A liver biopsy is essential for the diagnostic workup of persistent neonatal cholestasis (NC). The differential diagnosis of NC is broad, including obstructive and non-obstructive causes. In addition, histologic features of certain disorders may be non-specific in the early course of the disease. To evaluate liver biopsies using a practical histopathologic approach for NC and to define a simple scoring system for biliary atresia (BA) for routine clinical practice. From June 2006 to December 2021, liver biopsy specimens from infants with persistent NC were examined by two independent pathologists. The cases diagnosed as BA were correlated with clinical, radiologic, and laboratory data to calculate the final score. Four hundred and fifty-nine cases were enrolled in the study. They had a mean age of 63.94 ± 20.62 days and were followed for a median time of 58 (1–191) months. They included 162 (35.3%) cases of BA. On multivariate analysis, portal edema, ductular proliferation, cholangiolitis, and bile duct/ductular plugs were the histopathologic predictors of BA. A liver biopsy did perform well with a 95.1% sensitivity, 91.6% specificity, 86% PPV, and 97.1% NPV. At a cutoff of 5 of the scoring system, diagnosis of BA could be done with a sensitivity of 95.1% and a specificity of 100%. We have shown detailed histopathologic features of BA with more depth to infants aged ≤ 6 weeks. We have developed a simple scoring system using a combination of liver biopsy with non-invasive methods to increase the diagnostic accuracy of BA.

Protocols of Investigation of Neonatal Cholestasis-A Critical Appraisal.

Neonatal cholestasis (NC) starts during the first three months of life and comprises extrahepatic and intrahepatic groups of diseases, some of which have high morbimortality rates if not timely identified and treated. Prolonged jaundice, clay-colored or acholic stools, and choluria in an infant indicate the urgent need to investigate the presence of NC, and thenceforth the differential diagnosis of extra- and intrahepatic causes of NC. The differential diagnosis of NC is a laborious process demanding the accurate exclusion of a wide range of diseases, through the skillful use and interpretation of several diagnostic tests. A wise integration of clinical-laboratory, histopathological, molecular, and genetic evaluations is imperative, employing extensive knowledge about each evaluated disease as well as the pitfalls of each diagnostic test. Here, we review the difficulties involved in correctly diagnosing the cause of cholestasis in an affected infant.

Knowledge and Practice of Pediatric Providers Regarding Neonatal Cholestasis in the Western Region of Saudi Arabia.

Background:Early detection of neonatal cholestasis (NC) is important for better clinical outcomes but can be challenging.Objective:The objective of this study was to evaluate the knowledge and practice styles of pediatric providers (PPs) regarding NC in the western region of Saudi Arabia.Methods:This cross-sectional, questionnaire study was conducted between November 2019 and February 2020 in three major cities of the western region of Saudi Arabia (namely, Taif, Makkah and Jeddah). PPs included pediatric residents, pediatric specialists, pediatric consultants and family physicians. The questionnaire included 15 items in five subscales (definition, causes, diagnosis and management of NC and knowledge of guidelines).Results:A total of 488 participants completed the questionnaire. Only 30.2% were aware of the correct definition of NC (P < 0.001). Two-thirds of the respondents did not consider a history of pale stool being important for evaluating NC. The importance of biliary atresia as a serious cause of NC was found to be significantly different between pediatric consultants and other pediatricians (P < 0.001). In cases of prolonged NC, 32.4% of the PPs refer to pediatric gastroenterologist. Only 18.9% of the respondents were aware of liver biopsy being the gold standard investigation of NC. The majority of the respondents (41.8%) used ursodeoxycholic acid as a supportive therapy of NC.Conclusions:This study found a significant deficit in the knowledge and practice styles of PPs in the western region of Saudi Arabia. These findings highlight the need for policymakers to develop educational materials for PPs to increase their knowledge of NC.

Evaluation of Visual Examination of Stool as A Screening Test for Infant with Prolonged Neonatal Cholestasis Namely Biliary Atresia

Introduction: Neonatal cholestasis is a hepatobiliay disease characterized by biliary obstruction in the neonatal period. Biochemically it is evidenced by prolonged elevation of serum conjugated bilirubin beyond the first 14 days of life.1 Most common causes are biliary atresia and idiopathic neonatal hepatitis.3, 4&#x0D; Objective: To evaluate stool color as a screening test by visual inspection in infants with prolonged neonatal cholestasis.&#x0D; Methodology: This was a cross-sectional analytic study, conducted in Pediatric Gastroenterology and Nutrition Department,BSMMU, Dhaka, from 3 September 2012 to 3 February 2013 about 6 month duration. Statistically calculated 38 infants with prolonged neonatal direct hyperbilirubinaemia beyond their 14 days of age were included in this study.&#x0D; Results: The mean age of the subjects was 62.3 days with a standard deviation (SD) ±13.7 days. Male to female ratio was 1.2:1. All (100%) the subjects were icteric and hepatomegaly was found in 94.7% subjects. Dark urine (84.2%), pale stool (78.5%), bleeding manifestations (31.8%) and infection (29%) were also observed. Thirty (78.5%) subjects had pale colored stool. Mean (± SD) albumin and conjugated bilirubin levels were 3.68 (±1.88)gm/dl and 5.29 (±1.31)mg/dl respectively. ALT and GGT level of the study subjects were 346.19±124.28 u/dl and 315±198.91 u/l respectively. Common ultrasonographic findings of the patients were non visualization of gallbladder 60.5%, non-visualization of common bileduct 50%, hepatomegaly 92.1%, and triangular cord sign in portahepatis 7.9%. Scintigraphy revealed impaired excretion into intestine 88.9% in majority of the subjects. Liver biopsy revealed liver architecture was preseved 65.8% bile duct proliferation 52.6%, regenarating nodule was absent 65.8% gaint cell was present 52.6% portal tract inflammation was found in 47.4%. Sensitivity of stool color in the diagnosis of neonatal cholestasis was found 90.6%, specificity 83.3%, accuracy 89.5%, positive predictive value 96.7% and negative predictive value 62.5%.&#x0D; Conclusion: It can be concluded that stool color might be reliable indicator for screening of prolonged neonatal cholestasis namely biliary atresia.&#x0D; J Bangladesh Coll Phys Surg 2021; 39(1): 46-52

Citrin deficiency mimicking mitochondrial depletion syndrome

BackgroundNeonatal intrahepatic cholestasis caused by citrin deficiency (CD) is a rare inborn error of metabolism due to variants in the SLC25A13 gene encoding the calcium-binding protein citrin. Citrin is an aspartate-glutamate carrier located within the inner mitochondrial membrane.Case presentationWe report on two siblings of Romanian-Vietnamese ancestry with citrin deficiency. Patient 1 is a female who presented at age 8 weeks with cholestasis, elevated lactate levels and recurrent severe hypoglycemia. Diagnosis was made by whole exome sequencing and revealed compound heterozygosity for the frameshift variant c.852_855del, p.Met285Profs*2 and a novel deletion c.(69 + 1_70–1)_(212 + 1_231–1)del in SLC25A13. The girl responded well to dietary treatment with a lactose-free, MCT-enriched formula. Her younger brother (Patient 2) was born 1 year later and also found to be carrying the same gene variants. Dietary treatment from birth was able to completely prevent clinical manifestation until his current age of 4.5 months.ConclusionsAs CD is a well-treatable disorder it should be ruled out early in the differential diagnosis of neonatal cholestasis. Due to the combination of hepatopathy, lactic acidosis and recurrent hypoglycemia the clinical presentation of CD may resemble hepatic mitochondrial depletion syndrome.

Etiologies of neonatal cholestasis at a tertiary hospital in Bangladesh

Background Neonatal cholestasis is an important etiology of chronic liver disease in young children. It has a varied etiology. There is considerable delay in presentation and diagnosis of neonatal cholestasis in Bangladesh. Lack of awareness and knowledge among the pediatricians regarding etiological diagnosis and outcome of neonatal cholestasis is the reasons for poor outcome in major portion of cases in Bangladesh.&#x0D; Objective To evaluate the etiological spectrum of neonatal cholestasis.&#x0D; Methods This retrospective study was conducted at the Department of Pediatric Gastroenterology and Nutrition, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. We reviewed medical records of children who were diagnosed with neonatal cholestasis. Complete diagnostic profiles of every cases with age of presentation, male-female ratio and final diagnosis were analyzed.&#x0D; Results A total of 114 children with neonatal cholestasis were evaluated. Subjects’ male-female ratio was 1.92: 1.0, and mean age at hospitalization was 92.7 (SD 39.5) days. Biliary atresia was the most common etiology (47.4%), followed by idiopathic neonatal hepatitis/INH (21.9%). Other identified etiologies were, toxoplasmosis, others (syphilis, varicella-zoster, parvovirus b19), rubella, cytomegalovirus (CMV), and herpes/TORCH infection (8.61%), progressive familial intrahepatic cholestasis/PFIC (4.4%), galactosemia (4.4%), choledochal cyst (3.5%), sepsis (1.8%), urinary tract infection/UTI (1.8%), hypothyroidism (1.8%), lipid storage disease/Niemann-Pick disease (0.9%), non-syndromic paucity of interlobular bile ducts (2.67%), and Caroli’s disease (0.9%).&#x0D; Conclusion In Bangladesh, neonatal cholestasis cases are most often due to obstructive causes, particularly biliary atresia. Idiopathic (INH), infectious (primarily TORCH), metabolic, and endocrine causes followed in terms of frequency.

Etiologies of neonatal cholestasis at a tertiary hospital in Bangladesh

Background Neonatal cholestasis is an important etiology of chronic liver disease in young children. It has a varied etiology. There is considerable delay in presentation and diagnosis of neonatal cholestasis in Bangladesh. Lack of awareness and knowledge among the pediatricians regarding etiological diagnosis and outcome of neonatal cholestasis is the reasons for poor outcome in major portion of cases in Bangladesh.&#x0D; Objective To evaluate the etiological spectrum of neonatal cholestasis.&#x0D; Methods This retrospective study was conducted at the Department of Pediatric Gastroenterology and Nutrition, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. We reviewed medical records of children who were diagnosed with neonatal cholestasis. Complete diagnostic profiles of every cases with age of presentation, male-female ratio and final diagnosis were analyzed.&#x0D; Results A total of 114 children with neonatal cholestasis were evaluated. Subjects’ male-female ratio was 1.92: 1.0, and mean age at hospitalization was 92.7 (SD 39.5) days. Biliary atresia was the most common etiology (47.4%), followed by idiopathic neonatal hepatitis/INH (21.9%). Other identified etiologies were, toxoplasmosis, others (syphilis, varicella-zoster, parvovirus b19), rubella, cytomegalovirus (CMV), and herpes/TORCH infection (8.61%), progressive familial intrahepatic cholestasis/PFIC (4.4%), galactosemia (4.4%), choledochal cyst (3.5%), sepsis (1.8%), urinary tract infection/UTI (1.8%), hypothyroidism (1.8%), lipid storage disease/Niemann-Pick disease (0.9%), non-syndromic paucity of interlobular bile ducts (2.67%), and Caroli’s disease (0.9%).&#x0D; Conclusion In Bangladesh, neonatal cholestasis cases are most often due to obstructive causes, particularly biliary atresia. Idiopathic (INH), infectious (primarily TORCH), metabolic, and endocrine causes followed in terms of frequency.

Evaluation of Cases with Neonatal Cholestasis

Amaç: Çalışmanın amacı, neonatal kolestaz nedeniyle takip edilen çocuk hastaların etiyoloji, tanı yöntemleri, laboratuvar bulguları, tedavi şekilleri ve uzun dönem prognozları açısından geriye dönük olarak incelenmesi amaçlandı. Gereç ve Yöntem: Yaşamın ilk üç ayında kolestazı olan hastalar çalışmaya alınmıştır. Hastalar ekstrahepatik kolestaz ve intrahepatik kolestaz olarak gruplandırılmıştır. Ekstrahepatik kolestaz grubu içerisine biliyer atrezi, koyulaşmış safra sendromu ve koledok kisti dâhil edilmiştir. Bunların dışında kalan hastalar intrahepatik kolestaz grubu içerisinde değerlendirilmiştir. Hastaların tanıları, yakınmaları, klinik seyirleri, laboratuvar bulguları ve tedaviye yanıtları incelenerek geriye dönük olarak prognozları değerlendirilmiştir. Bulgular: Çalışma grubu kolestaz tanısı alan hastalar 43’ü kız (%41), 62’si erkek (%59) cinsiyete sahip olmak üzere toplam 105 hastadan oluştu. Vakaların 46’sı (%43.8) prematüre doğmuştu. Otuz altı hasta (%34.3) 30-37 haftalar arasında; 10 hasta (%9.5) 30 haftanın altında olup, 39’unda ise (%37.1) düşük doğum ağırlığı mevcuttu. Hastaların %81’inde intrahepatik, %19’unda ekstrahepatik nedenlere bağlı kolestaz geliştiği saptandı. Akolik dışkı ekstrahepatik kolestaz vakaların %90’ında (18 vaka), intrahepatik vakaların %15.3’ünde (13 vaka) olmak üzere toplam 31 vakada görülmüştür. İntrahepatik kolestaz vakalarında doğum ağırlığının ekstrahepatik kolestaz vakalarına göre daha düşük olduğu saptandı. Klinik seyirlerinde intrahepatik kolestaz hastası 38 vaka (%44.7), ekstrahepatik kolestaz hastası 7 vaka (%35) düzeldi. Sonuç: Çalışmamızda, hastaların literatür oranlarından daha geç tanı aldığı görülmüştür. Bu gecikme özellikle biliyer atrezi vakalarının erken cerrahi müdahale şansını azaltmaktadır. Ultasonografik görüntülemede “triangular cord sign” belirtisinin literatürden farklı olarak hiç görülmemesi bu konuda eğitim ve tecrübe eksikliğinin olduğunu düşündürmüştür. Bunun dışında, GGT yüksekliği, spenomegali, doğum ağırlığı, akolik dışkılama gibi karaciğer hastalığı için anlamlı olacak bulguların gözden kaçması, tanı için hızlı davranılamaması çocuk hekimlerinin farkındalığını artırılması gerektiğine işaret etmektedir.

Neonatal Cholestasis: A Pandora's Box.

Neonatal cholestasis (NC) is a diagnostic dilemma frequently countered in a neonatal care unit. Early diagnosis is vital for achieving an optimal patient outcome as many causes of cholestasis such as biliary atresia are time-sensitive and amenable to treatment if analyzed and treated early. Nonetheless, it is not generally simple to analyze these cases right on time as some of them are regularly missed due to the presence of pigmented stools, lack of newborn metabolic screening, and named as instances of prolonged jaundice. In this manner, we prescribe to explore all reasons for prolonged jaundice stretching out past 14 days in neonates. Besides, we suggest that stool card ought to be a piece of release rundown for all newborn children being released from the nursery. This is of most extreme significance in the nation like India where guaranteeing customary follow-up is as yet a tough assignment. These stool cards will help in the early determination of patients with NC particularly biliary atresia and guarantee their auspicious cure. Another reason which needs exceptional say is parenteral nutrition–associated liver illness, as the proportion of preterm babies is getting greater and greater with better neonatal care. These extreme preterm infants are in the requirement for prolonged (>14 days) total parenteral nourishment because of which they are at high hazard for NC contrasted with their more developed peers. In this survey, we will give an understanding of clinical approach, differential diagnosis, and clinical review of NC.

Italian guidelines for the management and treatment of neonatal cholestasis.

Hyperbilirubinemia is a frequent condition affecting newborns during the first two weeks of life and when it lasts more than 14 days it is defined as prolonged jaundice. This condition requires differential diagnosis between the usually benign unconjugated hyperbilirubinemia and the pathological conjugated hyperbilirubinemia, that is mainly due to neonatal cholestasis. It is important that the diagnosis of neonatal cholestasis be well-timed to optimize its management, prevent worsening of the patient’s outcome, and to avoid premature, painful, expensive, and useless tests. Unfortunately, this does not always occur and, therefore, the Task Force on Hyperbilirubinemia of the Italian Society of Neonatology presents these shared Italian guidelines for the management and treatment of neonatal cholestasis whose overall aim is to provide a useful tool for its assessment for neonatologists and family pediatricians.

Can Neonatal Hepatitis Be More Fatal than Biliary Atresia?

Background/Aims: The basic problem in diagnosis of neonatal cholestasis (NC) is to differentiate biliary atresia (BA) from other non-obstructive disorders. Because if bile flow cannot be provided by surgery, BA leads to cirrhosis and death within the first year of life. The aim of the present study is to determine histopathological features that may help to differentiate BA from neonatal hepatitis (NH). Material and Methods: This retrospective study was carried out on 105 liver biopsy specimens of 74 infants with NC who were diagnosed between 2003 and 2012. Results: The mean age was 76.5 ± 40.64 days. The most valuable biopsy findings for the discrimination between NH and BA, in decreasing order of importance, were ductular proliferation (p < 0.001), cholestasis in neoductuli (p < 0.001), fibrosis (p = 0.002), and extramedullar hematopoiesis (p = 0.02). While Kasai operations were performed in 19 cases, liver transplantation was performed in 10 cases. Survival rate among the death cases with BA was longer than the survival time of the death cases with NH (p = 0.023). Currently more children live with a close to normal quality of life with portoenterostomy and/or liver transplantation. On the contrary, NH can be more fatal with associated disorders such as growth retardation, specific infections, respiratory distress, and metabolic or endocrine diseases.

Low Incidence of α-1 antitrypsin deficiency among babies with prolonged jaundice.

α-1 antitrypsin (AAT) deficiency is one of the most important genetic causes of childhood liver diseases in some parts of the world, but its geographic distribution is highly variable. There are many reports from Asian countries such as India, the Philippines, and China which show a very low incidence of this disease. However few studies exist from Iran regarding this genetic deficiency as the cause for prolonged neonatal jaundice. In this study we attempt to investigate the possible role of AAT deficiency as a cause of prolonged neonatal jaundice in the largest pediatric referral center of Southern Iran. We included 126 neonates with the clinical diagnosis of neonatal cholestasis in this study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed on the extracted DNA from their blood samples. DNA sequencing confirmed the results of the PCR-RFLP tests. All patients were genetically normal regarding level of AAT, i.e., all were MM homozygotes. AAT deficiency is a rare disease in Iran and is not a major cause of neonatal cholestasis in this country.

Diagnosis of neonatal cholestasis; outcome in a regional centre.

Aims Extrahepatic biliary atresia (EHBA), fatal without surgery, has a prevalence of 1 in 15000 births and an incidence of 50 cases per year. A Kasai operation before 8 weeks gives the best chance of survival with native liver. Quality clinicopathological care comprises early recognition of cholestatic jaundice, with prompt diagnosis and referral of cases of EHBA (or other causes of surgically correctable biliary obstruction) to super-regional centres for specialised surgery. This requires close cooperation between gastroenterologist and pathologist. Our aim was to assess the quality of our clinical and pathological contribution to this pathway. Methods We identified all infants over the last 12 years who had underdone liver biopsy for cholestatic jaundice. Every case had been discussed at clinicopathological conference. We examined the clinical and pathological records to establish initial diagnoses and subsequent outcome. Results *P Conclusions A close working relationship between the pathologist and the gastroenterologist at a regional centre, in partnership with the pathologists and hepatologists at super-regional centres, delivered effective care.

Differential diagnosis of neonatal cholestasis: clinical and laboratory parameters

To evaluate if clinical and laboratory parameters could assist in the differential diagnosis of intra and extra-hepatic neonatal cholestasis (NC). Retrospective study of NC patients admitted at the Pediatric Hepatology Outpatient Clinic of the teaching hospital of Universidade Estadual de Campinas (UNICAMP), Campinas, Brazil, between December 1980 and March 2005. The approach to the diagnosis of NC was standardized. According to diagnosis, patients were classified into two groups: I (intra-hepatic neonatal cholestasis) and II (extra-hepatic neonatal cholestasis). In order to verify if there was association with the categorical variable, the chi-square and Mann-Whitney tests were used, with corrections for age for the covariance analysis (ANCOVA). The determination of accuracy of the clinical and laboratory variables for differentiation of the groups was made using the analysis of the ROC curve. One hundred and sixty-eight patients were evaluated (group I = 54.8% and group II = 45.2%). In the patients with less than 60 days of life there was predominance of intra-hepatic causes, whereas, in those older than 60 days, there was predominance of extra-hepatic etiology (p < 0.001). Median birth weight was lower in group I (p = 0.003), as well as length at birth (p = 0.007). Median values of direct bilirubin were higher in group II (p = 0.006). Values of gamma-glutamyltransferase (GGT) (10 times higher than the limit of normality) presented sensitivity of 56.3%, specificity of 91.5%, and accuracy of 75.7% for the diagnosis of extra-hepatic cholestasis. In the present study, extra-hepatic NC presented greater weight and length at birth, fecal hypocholia/acholia, choluria, hepatomegaly, increase in GGT (10.8 times higher than the limit of normality), and a delay for investigation in the tertiary center.

Diagnóstico diferencial de colestase neonatal: parâmetros clínicos e laboratoriais

OBJETIVO: Avaliar se os parâmetros clínicos e laboratoriais poderiam auxiliar no diagnóstico diferencial da colestase neonatal (CN) intra- e extra-hepática. MÉTODOS: Estudo retrospectivo de pacientes com CN hospitalizados na Clínica de Hepatologia Pediátrica do Hospital de Clínicas da Universidade Estadual de Campinas (UNICAMP), Campinas (SP), entre dezembro de 1980 e março de 2005. A abordagem para o diagnóstico da CN foi padronizada. De acordo com o diagnóstico, os pacientes foram classificados em dois grupos: I (colestase neo natal intra-hepática) e II (colestase neonatal extrahepática). Para verificar se havia associação com a variável categórica, os testes de qui-quadrado e Mann-Whitney foram utilizados com correções para idade para a análise de covariância (ANCOVA). A determinação da precisão das variáveis clínicas e laboratoriais para a diferenciação dos grupos foi realizada através da análise da curva ROC. RESULTADOS: Cento e sessenta e oito pacientes foram avaliados (grupo I = 54,8% e grupo II = 45,2%). Nos pacientes com menos de 60 dias de vida, houve predominância de causas intra-hepáticas, enquanto que naqueles com mais de 60 dias, houve predominância de etiologia extrahepática (p < 0,001). A mediana de peso ao nascer foi mais baixa no grupo I (p = 0,003), assim como o comprimento ao nascer (p = 0,007). Os valores da mediana de bilirrubina direta foram mais altos no grupo II (p = 0,006). Os valores de gama glutamil transferase (GGT) (10 vezes mais altos do que o limite de normalidade) apresentaram sensibilidade de 56,3%, especificidade de 91,5% e acurácia de 75,7% para o diagnóstico de colestase extra-hepática. CONCLUSÃO: No presente estudo, a CN extra-hepática apresentou maior peso e comprimento ao nascer, hipocolia/acolia fecal, colúria, hepatomegalia, aumento de GGT (10,8 vezes mais alto do que o limite de normalidade) e um atraso no encaminhamento para a investigação no hospital terciário.

99mTc sestamibi imaging

Hepatobiliary scintigraphy is an integral part in the diagnostic work-up of the neonatal cholestasis syndrome. However, less than optimal specificity is its major disadvantage. Differentiation between biliary atresia and neonatal hepatitis is nearly impossible in some cases with poor hepatocellular function. 99mTc sestamibi (MIBI) is a cationic lipophilic agent which is a substrate of P-glycoprotein. This glycoprotein is normally expressed in biliary canalicular surfaces of hepatocytes. This property provides a hepatic excretory mechanism which is different from bilirubin excretion. In this study we evaluated the value of 99mTc MIBI in differential diagnosis of neonatal cholestasis. 20 infants with a mean age of 2.41 months (range, 0.1-5 months) were included in the study. Ten infants turned out to have extrahepatic biliary atresia and the other ten had neonatal hepatitis. Hepatobiliary (with 99mTc BrIDA) and 99mTc MIBI scintigraphy were performed for all the patients. 99mTc MIBI scintigraphy has shown bowel activity in all patients, including the patients with biliary atresia. Hepatobiliary scintigraphy revealed bowel activity only in five patients with neonatal hepatitis. Bowel visualization with 99mTc MIBI may be seen in patients with biliary atresia and 99mTc MIBI has limited value in differential diagnosis of neonatal cholestasis.

CD 56 staining in liver biopsies does not help in differentiating extrahepatic biliary atresia from other causes of neonatal cholestasis

IntroductionSeveral conditions are considered in differential diagnosis of neonatal cholestasis. Of these the most important is extrahepatic biliary atresia (EHBA), while prompt diagnosis and surgical correction of obstruction can ameliorate clinical symptoms, provides long term survival for about one fourth of patients and serves as an important bridge to transplantation for many others. From histopathologic standpoint, features of EHBA overlaps with other diagnoses and so ancillary tests such as immunohistochemical staining for CD56 is suggested by some authors as a helpful tool in differential diagnosis.Hereby we wanted to examine this staining in our center which is a referral children hospital and to prove its efficacy in our problematic cases.Materials and MethodsBy retrospective review of pathology records during 2000 to 2006 in Markaze Tebbi Koodakan (children hospital related to Tehran University of Medical Sciences), we selected 17 cases of EHBA as patients and 12 cases with other diagnoses as controls, both with some degree of bile ductular proliferation in liver biopsies. EHBA cases were all proved by surgery. Four of control cases also underwent surgery but proved to have open ducts by intra-operative cholangiography. Long term follow up and other tests ruled out EHBA in other 8 cases. Hematoxylin-Eosin stains of paraffin blocks were studied again and freshly prepared sections were immunostained for CD56.ResultsBile ducts and proliferating bile ductules were strongly positive for CD56 in 6 of 17 cases of EHBA. In 7 out of 17, positivity were seen in more than two thirds of portal tracts. In controls, one case showed strong positivity and 6 out of twelve showed positivity in more than two thirds of portal tracts. The intensity and distribution of CD56 staining did not differ significantly between two groups.DiscussionDespite findings of previous studies, we have shown that CD56 staining can not help as an ancillary test in differential diagnosis of neonatal cholestasis and perhaps other markers should be tested in this regard.

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

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. 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. 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). 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. 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.

Prevalence of Helicobacter pylori in Neonates and Young Infants Undergoing ERCP for Diagnosis of Neonatal Cholestasis

This study was carried out to determine the prevalence of Helicobacter pylori infection in 20 neonates and young infants from lower socioeconomic background undergoing endoscopic retrograde cholangiopancreatography (ERCP) examination for diagnosis of neonatal cholestasis. One young asymptomatic infant (5%) who was breast-feeding with complementary formula had H. pylori infection. Endoscopy showed a normal appearing mucosa and histology demonstrated mild superficial acute gastritis. A follow-up gastroscopy performed 14 months after the initial study showed normal histology without evidence of H. pylori, suggesting that the infection was transient. Nineteen (95%) of the 20 mothers had H. pylori infection, including the mother with the infant positive for H. pylori. All mothers had gastritis on biopsy specimens. Despite the high prevalence of H. pylori in the mothers, infection in neonates and young infants was uncommon.

Efficacy of hepatobiliary scintigraphy in the differential diagnosis of neonatal cholestasis and postoperative follow-up after hepatoportodigestive anastomosis

Efficacy of hepatobiliary scintigraphy in the differential diagnosis of neonatal cholestasis and postoperative follow-up after hepatoportodigestive anastomosis