Variant etiologies of neonatal cholestasis and their outcome: a Middle East single-center experience.

AIM OF THE STUDY: Neonatal cholestasis (NC) constitutes a large proportion of pediatric liver disorders. Nevertheless, awareness of the variant etiologies and how to manage them appropriately are lacking. So, out of a few specialized centers, many cases pass without appropriate management. This study aimed to present our tertiary level center's experience in NC that could increase the pediatrician's awareness of handling this problematic and common medical morbidity efficiently. MATERIAL AND METHODS: It is a retrospective study in which we analyzed the NC cases admitted to the inpatient department within three years. For all recruited patients, the available data were retrieved and recorded. RESULTS: A total of 412 patients were reviewed with 20 different etiologies diagnosed. The most common cause was biliary atresia (n = 151, 37%), followed by progressive familial intrahepatic cholestasis (n = 51, 12%), neonatal sepsis (n = 39, 9%), and cytomegalovirus (n = 33, 8%). Of the 412 patients, 394 (81%) had follow-up ranging from 1 to 36 months. A total of 173 patients improved with supportive and/or specific therapy, while 108 patients died at a median age of 6 months. The commonest cause of death was liver failure (40.7%), followed by pneumonia (28.7%), sudden death (13%), septicemia (6.5%), and hepatorenal syndrome (5.5%). CONCLUSIONS: NC constitutes more than one-third of the inpatient admissions of all pediatric liver disorders and has a high rate of mortality. Awareness of the variety of etiologies and a rapid stepwise approach to diagnosis could have an impact on the outcome of this devastating disease.

Von Willebrand factor and esophageal varices in children with chronic liver diseases.

Aim of the study: To evaluate the role of plasma level of von Willebrand factor antigen (vWF-Ag) as a possible predictor for the presence of esophageal varices (EVs) in children with chronic liver diseases (CLDs). Material and methods: All patients underwent upper esophagogastroduodenoscopy (EGD) and were categorized as group I (had EVs) and group II (had no EVs). The following patient data were determined: Child-Pugh score (CPS), plasma vWF-Ag, vWF-Ag/thrombocyte ratio (VITRO) score, aspartate transaminase (AST) to platelet ratio index (APRI) score, AST/alanine transaminase (ALT), platelet count/spleen diameter, grading of EVs (small, medium and large) and categorizing the stage of liver fibrosis. Results: The analysis included 50 patients with CLD; 30 (60%) were female. The commonest etiological diagnoses were autoimmune hepatitis (AIH) (20%) and extra-hepatic biliary atresia (EHBA) (12%). 26% of cases were categorized as undiagnosed CLD. The CPS showed CPS-A 34%, CPS-B 44% and CPS-C 22%. The vWF-Ag was found at a high level of 243.52 ±195.97, with a highly statistically significant difference in discriminating the EVs with 74% accuracy at a cut-off value of 108.99 IU/ml, p < 0.0001. Also, ROC analysis was performed for discriminating large esophageal varices with 84% accuracy at a cut-off value of 475.85 mg%. The VITRO score at a cut-off value of 1.72 could detect EVs with 70% sensitivity, 86.7% specificity, and 80% accuracy. Conclusions: High vWF-Ag is a valuable prognostic tool for estimating the presence of EVs, and higher vWF-Ag is associated with increased grade of EVs.

First report of glycogen storage disease type 111a in a Nigerian child.

Glycogen storage disease (GSD) is a rare inborn error of metabolism with an incidence of 1/20,000-40,000 live births. Some of the presenting clinical features can mimic diseases commonly seen in the tropics and subtropics. We report a 14-month-old Nigerian child who presented at our institution with GSD Type 111a to alert physicians on the need to consider and recognise this rare disorder. The child presented with progressive abdominal swelling due to marked hepatomegaly. From the clinical history, the only clue to hypoglycaemia was that she eats very frequently. Her random blood sugar was normal; however, fasting blood sugar was low. The diagnosis was further entertained with laboratory results showing hypercholesterolaemia and uricaemia and confirmed by histology of biopsied liver tissue. GSD should be suspected in a child with unexplained hepatomegaly and investigated accordingly.

Urinary urobilinogen in biliary atresia: A missed, simple and cheap diagnostic test.

AIM: Early diagnosis of biliary atresia (BA) is of utmost importance for good outcome; however, it is sometimes difficult due to the overlapping diagnostic test results with other causes of neonatal cholestasis. Moreover, many diagnostic tests are costly, invasive and not available in all centers, especially in developing countries. So, we aimed to investigate the diagnostic performance of urinary urobilinogen; an easy, cheap test that was not tested before in BA. METHODS: Seventy-five infants divided into three age- and sex-matched groups (BA, non-BA cholestasis and healthy control group) were recruited for the study. Each group comprised 25 infants. Urinary urobilinogen was measured for all infants using the modified Ehrlich's method. RESULTS: Urinary urobilinogen was significantly lower in the BA group (0.31 ± 0.25 mg/dL) than both of the non-BA cholestasis (2.08 ± 3.48 mg/dL) and healthy control (0.53 ± 0.64 mg/dL) groups at P < 0.0001 and P < 0.001, respectively. Urinary urobilinogen at a cut-off value of 0.32 mg/dL or less can differentiate BA from other non-BA cholestasis with a sensitivity of 88% and a specificity of 72%. When this cut-off value was combined with γ-glutamyltransferase (γ-GT) at a cut-off value of 363 U/L or more, BA could be differentiated from other cholestatic disorders with a sensitivity of 80% and specificity of 100%. On the other hand, dipstick test could not differentiate between BA and non-BA cholestasis (P = 0.396). CONCLUSION: Urinary urobilinogen is a simple, non-invasive, cheap, sensitive and specific marker, especially if combined with γ-GT, which can be used in diagnosis of BA, especially in developing countries.

Design and validation of a diagnostic score for biliary atresia.

BACKGROUND & AIMS: The dilemma of early diagnosis of biliary Atresia (BA), particularly distinguishing it from other causes of neonatal cholestasis is challenging. The aim was to design and validate a scoring system for early discrimination of BA from other causes of neonatal cholestasis. METHODS: A twelve-point scoring system was proposed according to clinical, laboratory, ultrasonographic, and histopathological parameters. A total of 135 patients with neonatal cholestasis in two sets were recruited to design (n=60) and validate (n=75) a scoring system. Parameters with significant statistical difference between BA (n=30) and non-BA (n=30) patients in the design set were analyzed by logistic regression to predict the presence or absence of BA then a scoring system was designed and validated. RESULTS: The total score ranged from 0 to 37.18 and a cut-off value of >23.927 could discriminate BA from other causes of neonatal cholestasis with sensitivity and specificity of 100% each. By applying this score in the validation set, the accuracy was 98.83% in predicting BA. The diagnosis of BA was proposed correctly in 100% and the diagnosis of non-BA was proposed correctly in 97.67% of patients. By applying this model, unnecessary intraoperative cholangiography would be avoided in non-BA patients. CONCLUSIONS: This scoring system accurately separates infants with BA and those with non-BA, rendering intraoperative cholangiography for confirming or excluding BA unnecessary in a substantial proportion of patients.

Value of hepatic subcapsular flow by color Doppler ultrasonography in the diagnosis of biliary atresia.

BACKGROUND AND AIM: Diagnosis of biliary atresia (BA), particularly distinguishing it from other causes of neonatal cholestasis (NC), is challenging. Ultrasonography is a helpful investigation when evaluating NC. The aim was to determine the value of color Doppler ultrasound, particularly hepatic subcapsular flow, as a possible tool in early discrimination of BA from other causes of NC. METHODS: Ultrasonographic and color Doppler findings of 27 BA patients were compared with that in 27 non-BA cholestasis patients and a control group of 22 non-hepatic neonates. RESULTS: Hepatic artery diameter was significantly higher in BA (2.48 ± 0.55 mm) than that in non-BA group (1.91 ± 0.63 mm) (P = 0.001) and the control group (1.6 ± 0.47 mm) (P < 0.0001), while there were no statistically significant difference between BA and non-BA groups as regards portal vein diameter and flow, hepatic vein flow, and hepatic artery resistance index. The frequency of hepatic subcapsular flow was significantly higher in BA than that in non-BA group (96.3% vs 3.7%; P < 0.0001), while it was not detected in any of the non-hepatic control group. The presence of hepatic subcapsular flow had 96.3% sensitivity and specificity in predicting BA. CONCLUSIONS: Color Doppler ultrasound findings could help significantly in discriminating BA from other causes of NC, among which hepatic subcapsular flow had the best performance. Considering the young age of BA patients (61.8 ± 15.1 days), hepatic subcapsular flow can help in early diagnosis of BA and prevent the delay in surgical correction.

Differential hepatic expression of CD56 can discriminate biliary atresia from other neonatal cholestatic disorders.

OBJECTIVES: The diagnosis of biliary atresia (BA) can be challenging as its histopathologic features overlap with those of other pediatric cholestatic liver diseases. We aimed to study the diagnostic value of hepatic CD56 immunostaining in the differentiation of BA from other causes of neonatal cholestasis. METHODS: Hepatic CD56 immunostaining was investigated in 30 infants with BA and compared with that in 30 infants with non-BA cholestatic disorders. The expression of positive cells was interpreted semiquantitatively on the basis of the extent (percentage or number) of positive cells on a scale of 0-3. RESULTS: The occurrence of CD56-positive biliary epithelial cells was significantly higher in the BA (83.3%) than in the non-BA group (6.7%), whereas the occurrence of CD56 natural killer cells in hepatic parenchyma was significantly higher in the non-BA group (76.7%) than in the BA group (6.7%; P<0.0001 for both). In contrast, there was no significant difference between both groups in CD56 natural killer cells in portal tracts (P>0.05). Using this differential expression as a discriminative tool between the BA and the non-BA group, positive biliary epithelial cell staining had high specificity, whereas negative parenchymal staining had high sensitivity (93.3% for both) with an accuracy of 88.3 and 84.65%, respectively. The combination of both parameters improved the accuracy up to 91.65%, with 100% specificity in the diagnosis of BA. CONCLUSION: CD56 immunostaining of the liver had a diagnostic value; it can be used to differentiate BA from other neonatal cholestatic disorders and might be useful as an additional stain when investigating infants with neonatal cholestasis.