Idiopathic Neonatal Hepatitis Research Articles

Early Childhood Cholestasis, Causes & Associated Factors in Children

Background: Newborn cholestasis is explained as a persisted rise of the serum conjugated bilirubin outside the first two weeks of life. There are many etiologies of newborn cholestasis that must be differentiated since immediate interference may give a better outcome. Objective: Newborn cholestasis is explained as a persisted rise of the serum conjugated bilirubin outside the first two weeks of life. There are many etiologies of newborn cholestasis that must be differentiated since immediate interference may give a better outcome. Patients and Methods: A cross-sectional research of forty-eight children consulting the Childhood Wellbeing Teaching Hospital in Baghdad/Medical City from 1st of November 2018 to the 30th of November 2021, complete evaluation by full history, physical checkup and laboratory studies. Cholestasis was demarcated as an extended raise of the levels of conjugated bilirubin outside the 1st 2 weeks of age above 1.0mg/dl(17.1µmol/l) if the whole serum bilirubin(TSB) is <5.0 mg/dL or above 20% of the TSB if the TSB is >5.0 mg/dl. Results: Out of 48 children involved in the study ,62.5% resided in Baghdad, and the remainder was belonged to other districts. The mean age of children was 11.1 months. The males constituted 58.3% of them. Eleven cases (22.9%) were caused by congenital infection, nine 18.8% had no cause detected, while 16.7% caused by biliary atresia and 16.7% had unidentified etiology, however 10.4% was related to sepsis. Biliary atresia was more frequent in boys in 62.5% compared to 37.5% in females. Family history was positive only in11.1% of idiopathic neonatal hepatitis. It was found that 81% of cholestatic jaundice were caused by congenital infection. In comparison, 62.5% caused by biliary atresia and 60% caused by sepsis appeared on the second week of the child's age, and this difference was significant statistically P-value 0.01. Conclusion: Innate infections are the most frequent source, where CMV contagion is the most commonly detected. Clinical findings included clay colored stool & elevated alkaline phosphatase concentrations observed primarily on biliary atresia. There are no specific test to identify the etiology of newborn cholestasis.

Comparison of different diagnostic methods in infants for differentiating idiopathic neonatal hepatitis from biliary atresia

Background: Biliary atresia (BA) and idiopathic neonatal hepatitis (INH) are two most common etiologies of neonatal cholestatic jaundice. It is important to distinguish INH from BA biliary atresia in an infant. The study was conducted to compare of different diagnostic methods in infants in differentiating INH and BA. Methods: This cross-sectional study was conducted at the Department of Pediatric Gastroenterology & Nutrition, BSMMU during the period from July 2018 to June 2019 among infants with neonatal cholestasis. Total 50 cholestatitic cases were selected through purposive sampling. A thorough history and physical examination were done and liver enzymes were studied. Abdominal ultrasonography, hepatobiliary scintigraphy and liver biopsy were done in all cases. Clinical parameter and investigational sensitivity, specificity, and diagnostic precision were calculated. To diagnose BA and INH, liver biopsy was considered the gold standard. Results: Among the participants, 72% were diagnosed as BA and 28% were INH. More than half of patients were male. There exists significant difference of birth weight and term baby between BA and INH. Presence of persistent pale coloured stool was more commonly seen in patients with BA. Diagnostic accuracy of persistent pale coloured stool, birth weight (normal) and term baby were 94%, 92% & 88% respectively. Sensitivity and specificity of Gammaglutamyl transpeptidase (GGT) in differentiating cases with BA and INH with cut point of ≥430.0 U/L were 86.1% and 85.7%, respectively. Hepatobiliary scintigraphy is found to have a better sensitivity than ultrasonography. GGT had diagnostic accuracy 86%, hepatobiliary scintigraphy had diagnostic accuracy 88% & USG had diagnostic accuracy 80% for BA and INH. Conclusion: Among the studied clinical parameters persistent pale coloured stool was most accurate to suggest the presence of BA. Serum level of GGT at cut-off value ≥ 430 U/L may be used as a reliable laboratory parameter to differentiate INH and BA. Hepatobiliary scintigraphy found to have a good sensitivity for BA. Positive result of hepatobiliary scintigraphy may be used as BA in infants with cholestasis. JOPSOM 2023; 42(1):14-20

Patterns and unique features of infantile cholestasis among Arabs.

Most of the literature on infantile cholestasis (IC) originated from Caucasian and Asian populations. The differential diagnosis of IC is very broad, and identification of etiology is challenging to clinicians because the list includes many entities with overlapping clinical, biochemical, and histological features. Thus, a structured, stepwise diagnostic approach is required to help early recognition and prompt evaluation and management of treatable causes of cholestasis. (1) To determine the differential diagnosis of IC among Saudi population and (2) to evaluate the usefulness of a diagnostic algorithm that has been tailored by the authors to the local practice. All infants with onset of cholestasis before 12 months of age (2007 and 2020) were identified and included if they underwent extensive work up to exclude infectious, structural, metabolic, endocrine, infiltrative, and familial causes. Our diagnostic pathway allowed a definite diagnosis in 373 of the included 533 cases; 160 (30%) were labelled as "idiopathic neonatal hepatitis" (INH) [i.e., overall 70% detection rate]. However, when considering the cases that underwent extensive investigations including advanced gene testing (415 of the 533), the yield of the diagnostic algorithm was 90% (373/415). Familial cholestasis group was the most common in 20% (107/533), and biliary atresia and neonatal-onset Dubin Johnson syndrome contributed to 6% each. The genetic/hereditary causes of cholestasis contributed to 58% of the diagnosed cases (217/373). No single case of alpha-1 antitrypsin deficiency was diagnosed. Forty-nine infants with cholestasis presented with liver failure (9%). Our study highlights several unique features and causes of IC among Arabs which could have a great impact on the differential diagnosis process and the choice of laboratory tests used in the clinical setting.

An Insight Into Neonatal Cholestasis; A Tertiary Care Hospital Experience in Rawalpindi, Pakistan

Objective: To determine the frequencies of various etiologies of neonatal cholestasis diagnosed by clinical findings and laboratory investigations at the Pak Emirates Military Hospital, Rawalpindi, Pakistan. Study Design: Cross-sectional study. Place and Duration of Study: Pediatric Department of Pak Emirates Military Hospital, Rawalpindi Pakistan, from Jan 2021 to Apr 2022. Methodology: Infants of either gender aged 14 days to six months admitted to Inpatient facility who had jaundice with direct bilirubin and more than 20% of total bilirubin were included in the study. The proforma was formulated to record the clinical features, laboratory investigations, weight, level of activity and consanguinity among the parents. Results: A total of 146 infants were included in the study. Jaundice was seen in 100% of infants, hepatomegaly in 66.4%, splenomegaly in 38.4%, followed by ascites in 25%. The most common aetiology of neonatal cholestasis was Biliary Atresia 26.7% in the extrahepatic Group, Idiopathic Neonatal Hepatitis 25.3% in the intrahepatic Group. Consanguinity was present in parents of 65% of infants. Conclusion: The most common aetiology of extrahepatic Neonatal Cholestasis was Biliary Atresia, while Idiopathic Neonatal Hepatitis and Progressive Familial Intrahepatic Cholestasis were the most common causes of intrahepatic cholestasis.

Clinical and laboratory evaluation of cholestatic jaundice in a sample of Iraqi infants

Cholestatic jaundice most probably occurs due to a pathological condition moreover difficult diagnostic problem. The aim of the study: to determine the etiology of cholestatic jaundice in infancy and to evaluate if clinical events and different investigations could assist in the differential diagnosis of intra and extra-hepatic cholestasis. In this hospital-based study analysis of 35 cases diagnosed with cholestatic jaundice aged 3 weeks up to 12 months from two centers carried out from January 2018 to July 2018. Clinical, biochemical, radiological, histopathological results were recorded. Results: Regarding the 35 patients were (54.3% males, 45.7% females), the mean age at presentation was 117.9 ± 86.4 days and mean age at onset of jaundice was 34 ± 59.11 days, All patients were presented with jaundice (100%) and (45.7%) of them were presented with clay color stool, (77.1%) of patients presented with hepatomegaly followed by ( 54.3%) with splenomegaly, regarding the etiology of cholestasis, Extrahepatic biliary atresia was the commonest cause (22.9%) and the most common cause of intrahepatic etiology was Cytomegalovirus (14.3%). While Idiopathic neonatal hepatitis, Alagille syndrome were (8.6%) for each. Progressive familial intrahepatic cholestasis, Galactosemia, Tyrosinemia, and septicemia were (5.7%) for each. Congenital rubella and congenital hypothyroidism and Fatty acid oxidation disorder were (2.9%) for each. Undiagnosed patients represented (14.3%) of all cases. Inconclusion, the etiologies of infantile cholestatic jaundice are numerous. and was no single laboratory investigation that could precisely make a definite diagnosis. Extrahepatic biliary atresia was the most common cause of cholestasis in this study. Jaundice, hepatomegaly, and pale stools were the common clinical features on presentation.

Factors Predictive of an Obstructive Pathology among Filipino Infants with Neonatal Cholestasis

Objective. To determine factors predictive of obstructive neonatal cholestasis among Filipino infants and to describe their outcome.
 Methods. 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.
 Results. 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.
 Conclusion. 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.

Ultra-structural and histopathological features of liver biopsy taken during laparotomy to confirm the diagnosis of biliary atresia.

Neonatal cholestasis is caused by a group of diseases that cause jaundice, which can be encountered in the neonatal period. Biliary atresia (BA) and idiopathic neonatal hepatitis (INH) are among neonatal cholestasis diseases. The aim of this study was to perform histopathological and ultra-structural examinations of liver biopsy tissue samples from BA and INH patients with liver biopsies taken during laparotomy to confirm the diagnosis of biliary atresia. A total of patients undergoing Kasai surgery before the age of 60 days were included in an "early" group (n = 7), whereas patients undergoing surgery after the age of 60 days were included in a "late" group (n = 11). The control group (n = 11) included INH patients. For histopathological examinations, liver tissue samples obtained intra-operatively were subjected to routine histopathological procedures after being stained with caspase-3 and cytokeratin-7 antibodies. Ultra-structural evaluations were also performed. Statistical analysis used: For comparisons between the groups, a one-way analysis of variance (ANOVA) test and the Mann-Whitney U test were used for continuous variables. Histopathological findings reflected the specific liver pathologic findings seen in biliary atresia. Although there was no significant difference between the BA groups, these parameters were not detected in the control group. The histopathological evaluations revealed no significant differences in the findings of liver parenchyma damage between the early, late, and control groups. Electron microscopic examinations showed that the patients in the late group had more severe signs of intra-cellular damage to the liver. Although the histopathological examination revealed no significant differences in liver damage between the three groups, in ultra-structural evaluation, intra-cellular damage was found to be less in groups with better prognosis. Electron microscopy evaluations of intra-cellular damage may be more useful in this respect.

Etiology and outcome of neonatal cholestasis: an experience in a tertiary center of Bangladesh

BackgroundNeonatal cholestasis (NC) is a major cause of morbidity and mortality in young infants. This study examines the etiology of NC and its outcome during 2 years of follow-up at a tertiary referral center in Bangladesh.ResultsOut of 80 cholestatic infants, 60% had intrahepatic cholestasis with a mean age of onset of 12.4±2.8 days and a mean age of admission of 82.4±29.0 days. The remaining 40% were extrahepatic with a mean age of onset of 6.7±2.3 days and a mean age of admission of 94.6±50.4 days. Biliary atresia (BA), idiopathic neonatal hepatitis (INH), and TORCH (Toxoplasma, rubella, cytomegalovirus, and herpes simplex) infection except rubella were the most common causes. After receiving treatment, 46.2% of the cases improved, 23.8% deteriorated with morbidity, and 30% died. The majority of the children with INH, TORCH, choledochal cyst, hypothyroidism, galactosemia, and urinary tract infection (UTI) with sepsis were improved. Significant mortality was found in BA (56.6%), intrahepatic bile duct paucity (PIBD) (100%), and progressive familial intrahepatic cholestasis (PFIC) (100%) whereas the rest of BA (43.4%) live with persistent morbidity. Significant clinical improvement was observed in 37 (46.2%) cases of cholestasis evidenced by decreasing jaundice, change of color of urine from dark to normal color, change of stool color from pale to yellow, and gradual decrease in liver size from hepatomegaly state. In addition, decreasing median total bilirubin, direct bilirubin, alanine transaminase, gamma-glutamyl transferase, and alkaline phosphatase showed biochemical improvement at 2 years follow-up. The age of admission, etiology, and presence of ascites are the predictors of outcomes.ConclusionBA was the most common cause of extrahepatic while INH and TORCH infection were the most common cause of intrahepatic cholestasis. Majority of children with intrahepatic cholestasis improved but deteriorated with BA and genetic causes. Prompt referral and early diagnosis as well as the etiology of NC were the main determinants of the favorable outcome.

Seorang Anak Laki-Laki dengan Kolestasis, Cytomegalovirus dan Anemia: Laporan Kasus

Introduction: Cholestasis can cause obstruction of substances that should be secreted into the duodenum for further digestive process. Causes of intrahepatic cholestasis in children less than 2 months of age include idiopathic neonatal hepatitis; infections such as Cytomegalovirus (CMV), Human Immunodeficiency Virus (HIV), toxoplasmosis, Urinary Tract Infection (UTI), sepsis; and metabolic disorders, resulting from long-term administration of Total Parenteral Nutrition, and part of a syndrome. The infection can be transmitted either vertically or horizontally. Objective: This case report aims to determine congenital infections that can occur in children during pregnancy. Method: This study is a case report that applies a descriptive observational method about a 2.5-month-old boy being treated at Dr. Kariadi Semarang with a diagnosis of cholestasis, cytomegalovirus, normochromic microcytic anemia. Data was obtained from primary and secondary sources. Results and discussion: This case report explains that transmission of CMV infection can occur from mother to fetus during pregnancy, thus causing congenital infection. This infection becomes a chronic infection in children, thus affecting Hb levels in the blood and causing anemia. Examination of bilirubin, liver enzymes, and ultrasound of the abdomen confirmed the diagnosis of cholestasis. A head CT scan and ABR test are important for long-term monitoring. Conclusion: Infections that occur in patients due to cytomegalovirus may be acquired intrauterine. Complete investigations are needed to establish the diagnosis, so that appropriate therapy can be given. Long-term monitoring is important for the presence of intracranial calcifications as well as hearing loss.

Differentiating Biliary Atresia From Idiopathic Neonatal Hepatitis: A Novel Keratin 7 Based Mathematical Approach on Liver Biopsies.

Differentiating biliary atresia (BA) from idiopathic neonatal hepatitis (INH) is vital in routine pediatric practice. However, on liver biopsy, few cases offer a diagnostic challenge to discriminate these entities with certainty. Bile ductular reaction (DR), intermediate hepatobiliary cells (IHBC) and extra-portal ductules (EPD) indicate progenitor cell activation, as a response to various hepatic insults. The present study aims to quantify DR, IHBC and EPD by Keratin 7 (CK7) immunohistochemistry (IHC) in BA and INH and to devise a mathematical approach to better differentiate the two, especially in histologically equivocal cases. A total of 98 cases were categorized on biopsy as BA, INH or equivocal histology, favoring BA or INH. CK7 DR mean, IHBC mean and EPD mean values were compared between BA and INH. A formula was derived to help distinguish these two entities, the cut-off value, sensitivity and specificity of which were determined by receiver operating characteristic (ROC) curve. This formula was applied and validated on histologically equivocal cases. Univariate logistic regression revealed significant difference between BA and INH with respect to CK7 DR and CK7 EPD mean (p < 0.001 in both); however, CK7 IHBC mean was not significant (p = 0.08). On multivariate logistic regression, only CK7 DR had significant impact on diagnosis (p < 0.001). A formula: (CK7 DR)2 + (CK7 EPD)/(CK7 IHBC) was derived to help distinguish BA from INH. Cut off value of 10.5 and above, determined by ROC curve, favored a diagnosis of BA (sensitivity= 93.4%, specificity= 94.6%). Histologically equivocal and discrepant cases could be correctly categorized using this formula. Formula using CK7 IHC parameters may aid pathologists better distinguish BA from INH, especially in histologically equivocal cases.

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

DIFFERENTIATING BILIARY ATRESIA FROM OTHER CAUSES OF CHOLESTASIS JAUNDICE IN INFANTS

Aim: The aim of this study is to find out the cholestatic etiologies in infants and differences of clinical features, laboratory investigations between biliary atresia and other causes of cholestasis at Vietnam Children Hospital. Background: Cholestasis is defined as reduced bile formation or biliary flow. It results of varied causes. Early detection of biliary atresia is to intervene in time and have the best outcome. Patient and methods: In this retrospective study, 305 infants under 12 months of age with cholestasis were studied in Vietnam Children Hospital during 1/2017-7/2018. Demographic data, duration of jaundice, signs and symptoms as well as laboratory, imaging, liver biopsy and the causes of cholestasis were recorded, divided into 2 group BA and Non-BA. Results: 305 infants (194 boys, 111 girls) with cholestasis and mean age of 83,22±72,10 days were included in the study. The most common causes of cholestasis were idiopathic neonatal hepatitis (33,8%), biliary atresia (25,9%), cytomegalovirus infection (21,6%). In BA group, pale stool (100%), Hepatomegaly (98,7%); increasing less AST, ALT, more GGT level than Non-BA. Find out GGT cutoff &gt; 212,05 UI/l in diagnosing BA. Conclusion: Biliary atresia and idiopathic neonatal hepatitis are the most common causes of infantile cholestasis. Pale stool, hepatomegaly and GGT elevation &gt; 212,05 UI/l are the most reliable tests for diagnosing BA.&#x0D;

Evaluation of Nutritional Status of Hospitalized Infants with Cholestatic Jaundice in a Tertiary Care Center in Bangladesh

Introduction: Nutritional management becomes crucial for the infants of cholestatic jaundice as they suffer from impaired digestion and absorption of fatty acid and fat soluble vitamins. Thus evaluation of nutritional status was done to identify undergoing malnutrition.&#x0D; Materials and Methods: It was a cross-sectional, prospective study done in the indoor patients department of paediatric gastroenterology and nutrition, BSMMU; since April 2016 to September 2016 (6 months). Purposive sampling was done from the infants (2 weeks to 12 months age) with cholestatic jaundice or having neonatal jaundice persisting more than 2 weeks. Linear regression analysis was done for correlation between different anthropometric variables.&#x0D; Results: Total 47 patients were enrolled in this study although 93 patients were admitted with cholestatic jaundice in that time period in the department. Most of them were found biliary atresia (61.70%) Idiopathic Neonatal Hepatitis (31.91%). Among anthropometric indices, Weight for length Z(WLZ) Score mean was -1.6 (±1.6), Triceps skin fold thickness (TST) mean 5.48 (±2.75) mm, and Subscapular skin fold thickness(SST) mean was 4.13 (±2.39)mm. Linear regression analysis of each variables done with other and found positive correlation between TST with WLZ Score and SST with WLZ score and found highly significant (p=0.008 in ANOVA) and (p=0.011 in ANOVA) respectively.&#x0D; Conclusion: Cholestatic babies were found mild to moderately malnourished in our study. Skin fold thickness was found to be an important early clinical marker for diagnosis of malnutrition which was found positively correlated with the standard procedure of anthropometry in our study.&#x0D; Medicine Today 2020 Vol.32(1): 10-14

A practical approach to the pathology of neonatal cholestatic liver disease.

Navigating the complexities of interpreting a liver biopsy performed on a neonate with conjugated/direct hyperbilirubinemia can be an arduous task given these biopsies are infrequently encountered. The list of entities is long and yet there are only a few histologic patterns of liver injury. The first step for the pathologist is to determine the histologic pattern, which will guide further inquiry into the useful clinical information to have while evaluating the biopsy. Ultimately, the goal is to identify those conditions that will benefit from early intervention. We begin with a review of biliary development to help understand what findings may be physiologic versus pathologic, particularly in premature infants. Then we review eight cases that cover the three most common histologic patterns of injury in patients with neonatal cholestasis: biliary obstructive, neonatal hepatitis, and paucity of intrahepatic bile ducts. The entities that serve as prototypes for these histologic patterns are covered, including biliary atresia, idiopathic neonatal hepatitis, and Alagille syndrome, along with rarer entities that have histologic overlap. The cases with accompanying tables and algorithms are intended to help place the histologic findings in the context of the overall clinical work-up, including genetic testing.

Neonatal Cholestasis: A Primer of Selected Etiologies.

Cholestasis refers to impairment in formation or excretion of bile. This can be due to defects in intrahepatic production of bile, defects in the transmembrane transport of bile, or mechanical obstruction to bile flow. Clinical features of cholestasis reflect the retention of components of bile (bilirubin, bile acids, cholesterol) in the body. In the neonatal period, hyperbilirubinemia can be categorized as either unconjugated (and often benign) hyperbilirubinemia, or conjugated hyperbilirubinemia due to cholestasis. It is for this reason that the first laboratory evaluation in a patient with jaundice, dark urine, and/or acholic stool is a fractionated bilirubin. This article serves as a practical primer for pediatric and neonatology trainees and covers common causes of neonatal cholestasis, as well as the diagnostic work-up and treatment. Causes that are discussed include biliary atresia, idiopathic neonatal hepatitis, gestational alloimmune liver disease, metabolic and genetic diseases, total parenteral nutrition cholestasis, and congenital infection. [Pediatr Ann. 2018;47(11):e433-e439.].

A quantitative image analysis using MRI for diagnosis of biliary atresia

PurposeBiliary atresia is a life-threatening disease that needs early diagnosis and management. Recently, MRI images have been used for the diagnosis of biliary atresia with improved accuracy of diagnosis when other imaging modalities such as ultrasonography are equivocal. This study aimed to evaluate the juxta-hilar extrahepatic biliary tree using MRI images to determine a quantitative value for diagnosing biliary atresia. Materials and methodsThis retrospective study was approved by the Ethical Committee at Mackey Memorial Hospital (IRB Number: 15MMHIS149e). Between January 2010 and December 2015, twenty-five patients with surgically confirmed biliary atresia were enrolled (age 18–65 days). Another 25 patients with clinically or surgically diagnosed idiopathic neonatal hepatitis (age 6–64 days) and 20 patients with non-hepatobiliary disease (age 6–65 days) were considered control group and normal subjects, respectively. The diameter of the enlarged, T2-hyperintense structure was measured using MRI images by two radiologists both blinded. The cut-off value for a biliary atresia diagnosis was obtained by area under the curve analysis. ResultsThe diameter of the T2-hyperintense structure at porta hepatis in biliary atresia (4.79 ± 1.14 mm) is larger than in idiopathic neonatal hepatitis (1.72 ± 0.42 mm) or in non-hepatobiliary disease (1.72 ± 0.35 mm) (p < 0.05). The optimum cut-off value for diagnosing biliary atresia was 3.1 mm with 98% sensitivity and 98% specificity. ConclusionThe value of the enlarged, T2-hyperintense structure measured on MRI images was significantly increased in biliary atresia and may be useful in diagnosing biliary atresia.

Frequency of Different Causes of Infant Cholestasis in a Tertiary Referral Center in South-East Iran

Objectives: This study reports frequency of different causes of infant cholestasis diagnosed by clinical and biochemical parameters as well as liver biopsy. Methods: Cholestasis persisting beyond two-weeks of age in 46 infants less than 6 months old was evaluated. A checklist including signs and symptoms, as well as laboratory, imaging and liver biopsy results was prepared. According to diagnosis, patients were classified into two groups: biliary atresia (BA) and non-biliary atresia (Non-BA) and results were compared between two groups. P value 91 days. The most common symptoms and signs were jaundice in 100% followed by hepatomegaly (78%), splenomegaly (52%), acholic stool (35%) and dark urine (37%). There were no significant differences between the two groups for age, gender, onset of jaundice and organomegaly. Patients in BA group experienced more acholic stool, abnormal AST, ALT and bilirubin (P < 0.05). The most common underlying causes of liver disease in study group were BA (30.4%) and idiopathic neonatal hepatitis (INH) in 30.4% followed by metabolic disorders. Conclusions: Sixty one percent of infants with cholestasis in present study had BA and INH. A systemic approach is the key for rapid diagnosis to rule out BA and other treatable disorders for a better outcome.

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.

Ocular findings in patients with cholestatic disorders of infancy: A single-centre experience

Background and study aimsNeonatal cholestasis can be associated with ocular findings that might aid in its diagnosis, e.g., Alagille syndrome (AGS) and Niemann Pick disease (NPD). We aimed to investigate the frequency of ocular manifestations in infants with cholestasis. Patients and methodsThis cross-sectional study included cholestatic infants presenting to the Paediatric Hepatology Unit, Cairo University Paediatric Hospital, Cairo, Egypt. All infants underwent examination of lid, ocular motility, anterior and posterior segments and measurement of intraocular pressure, cycloplegic refraction, ocular ultrasonography and vision. ResultsThe study included 112 infants with various cholestasis; 73 (65.2%) were males. The median age was 2months. Diagnosis was reached in 39 cases: 14 had AGS, 14 had biliary atresia (BA), 4 had NPD, 4 had post-haemolytic cholestasis, 2 had cytomegalovirus neonatal hepatitis, and one case had hepatorenal tyrosinaemia. Thirteen cases were probably having progressive familiar intrahepatic cholestasis (PFIC) type 1 or 2 considering their persistent cholestasis in the presence of normal gamma-glutamyl transpeptidase; 28 were left with a diagnosis of “idiopathic neonatal hepatitis” (INH), and 32 (28.6%) had no definite diagnosis. Ophthalmologic abnormalities were found in 39 cases (34.8%). The commonest finding was unilateral/bilateral optic nerve drusen in 12 (10.7%), followed by posterior embryotoxon in 11 (9.8%). Ocular findings were observed in 64.3% patients with AGS, 50% patients with NPD, 30.8% cases with suspected PFIC type 1or 2, 28.6% infants with INH, and 14.3% patients with BA. ConclusionOphthalmologic findings are not uncommon among cholestatic infants. Ophthalmologic examination should be routinely performed, including assessment of anterior segment, fundus examination, and ocular ultrasound.

Biochemical and molecular characteristics of citrin deficiency in Korean children.

Mutations in SLC25A13 cause citrin deficiency, which has three phenotypes: neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), failure to thrive and dyslipidemia caused by citrin deficiency (FTTDCD) and adult-onset type 2 citrullinemia (CTLN2). The purpose of this study was to determine the mutation spectrum and the clinical and biochemical characteristics of citrin deficiency in Korean patients. Thirty-four patients were diagnosed with citrin deficiency based on mutations in SLC25A13, as verified by direct sequencing and long PCR screening of a large transposon insertion. A total of 66 alleles from 33 unrelated families of 34 patients with citrin deficiency (27 NICCD, 2 FTTDCD and 5 CTLN2) were retrospectively identified. The common pathogenic alleles were IVS16ins3kb (33%), c.851_854del (30%) and c.1177+1G>A (12%), and three novel variants were identified. Levels of citrulline, threonine, methionine, tyrosine and arginine and the threonine-to-serine ratio were higher in children with neonatal intrahepatic cholestasis caused by NICCD compared with that in patients with idiopathic neonatal hepatitis (INH). We concluded that Korean patients with citrin deficiency showed the highest frequency of the IVS16ins3kb mutation and that plasma amino-acid profiles can be used to differentiate between NICCD and INH.