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

Background and Aims 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. Methods 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. Results 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. Conclusions Formula using CK7 IHC parameters may aid pathologists better distinguish BA from INH, especially in histologically equivocal cases.

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 > 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 > 212,05 UI/l are the most reliable tests for diagnosing BA.

Neonatal jaundice

The chapter on neonatal jaundice covers the pathophysiology of jaundice with an extensive differential for unconjugated and conjugated jaundice. It includes suggested investigations and management, as well as more detailed information on idiopathic neonatal hepatitis.

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.

Usefulness of clinical and laboratory parameters for differentiation of biliary atresia from idiopathic neonatal hepatitis: Experience in a tertiary care hospital of Bangladesh

Background: The two most common and important causes of neonatal cholestasis (NC) are biliary atresia (BA) and Idiopathic neonatal hepatitis (INH). There is no single test that can definitely differentiate these two entities. Objective: To evaluate the diagnostic accuracy of clinical and laboratory parameters for diagnosis of biliary atresia. Methods: This cross-sectional study was conducted at the department of Pediatric Gastroenterology and Nutrition of Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh, from August 2013 through July 2015 among purposively sampled infants with neonatal cholestasis. Results: Total 86 neonatal cholestatic cases were studied. Term baby and good birth weight are significantly higher in BA cases. The presence of persistent pale colored stool is significantly more in patients with BA (p 0.000). GGT is the only liver enzyme that was found to be useful differentiating BA from INH at a cut-off value ≥ 524U/L or 9.5 times higher than upper limit normal with sensitivity and specificity of 81.6% and 72.9% respectively. In the present study the diagnostic accuracy of persistent pale colored stool found to be highest (79.1 %). Conclusion: The present study showed that Persistent pale colored stool and serum level of GGT with a cut-off value ≥524 U/L or 9.5 times higher than upper limit normal can be considered as predictive markers for differentiation of Biliary atresia from Idiopathic neonatal hepatitis. CBMJ 2015 January: Vol. 04 No. 01 P: 30-36