Neonatal Biliary Atresia Research Articles

72 - Design and validation of a scoring system for diagnosing biliary atresia in neonates and infants based on diffusion tensor imaging and blood biochemistry tests

72 - Design and validation of a scoring system for diagnosing biliary atresia in neonates and infants based on diffusion tensor imaging and blood biochemistry tests

Indocyanine green faecal excretion holds potential for diagnosis of neonatal biliary atresia

Indocyanine green faecal excretion holds potential for diagnosis of neonatal biliary atresia

Recurrent subdural hematoma as presentation of neonatal biliary atresia: A case report

Biliary atresia is a congenital disorder of progressive and obliterative cholangiopathy, the most common cause of neonatal cholestasis, it can cause secondary vitamin-K deficiency bleeding due to the malabsorption of lipids and lipid-soluble vitamins due to cholestasis. We report a 46-day-old child presenting with cholestatic features complicated by subdural hematoma (SDH) and cerebral edema. On investigations, she was found to be having primary biliary atresia, for which she was operated but had a recurrence of the SDH on the opposite side.

Investigating the genetic profile of familial atypical cystic fibrosis patients (DeltaF508-CFTR) with neonatal biliary atresia.

Biliary atresia (BA) is a progressive inflammatory process of the biliary tree resulting in biliary obstruction. No single known genetic or environmental factor has been established to cause BA. Cystic fibrosis (CF) is a rare cause of neonatal cholestasis, and it has never been described in familial BA cases. Here, we investigate two siblings of first-degree consanguineous parents presenting with neonatal BA. Shortly after the Kasai operation, the proband developed severe respiratory symptoms attributable to a missed CF diagnosis. This was discovered after re-investigating the family history, which revealed a first-degree cousin with CF who did not manifest BA. Afterwards, we identified a pathogenic variant (DeltaF508) in CFTR in both BA-affected siblings along with their cousin. This intrigued us to study the molecular etiology behind the familial BA presentations, which exclusively contributed to BA-pathogenesis in BA-CF-affected siblings and not in their CF-only affected cousin. We applied a multistep approach to investigate the variant profile of both siblings' and their cousin's exomes. We curated the genes whose variants were shared by the BA-CF siblings but absent or heterozygous in their CF-only-affected cousin. Consequently, we identified three candidate genes (SNAPC4, UCK1, and ZHX2) besides CFTR. We propose that these genes act cumulatively or individually in inducing BA-pathogenesis-either by aggravating the biliary damage in the context of CF or increasing the susceptibility of BA as a separate CF-comorbidity. To our knowledge, this is the first report of DeltaF508 in CFTR with familial neonatal BA cases.

Diagnostic Value of Ultrasound Parameter in Neonatal Biliary Atresia Based on Histopathological Results (Ultrasound study of triangular cord sign and gallbladder abnormality)

Objective: Biliary atresia is an obliterative progressive disease that forms fibrotic tissue in the biliary tract in the neonatal phase. In some European countries, the reported incidence of biliary atresia varies between 1/14,000 and 1/20,000 live births. Ultrasound examination is the modality used to diagnose Biliary Atresia. Ultrasound assessed the sensitivity, specificity, and accuracy of the Triangular Cord Sign and gallbladder abnormality consisting of gallbladder contractility and wall echogenicity. We evaluated the diagnostic test results of Triangular Cord Sign and gallbladder contractility and wall echogenicity with ultrasound examination based on histopathological results of neonatal biliary atresia Material and Methods:This diagnostic test was performed retrospectively between January 2019 and December 2020 with consecutive sampling techniques. A total of 61 pediatric patients clinically diagnosed with biliary atresia underwent ultrasound examination of triangular cord sign and gall bladder abnormality examined by a pediatric radiologist. Histopathological results of liver biopsy specimens confirming biliary atresia were available for all those patients. Data were analysed to assess accuracy, sensitivity, specificity, PPV, and NPV of ultrasound compared with histopathology result Result: The Triangular Cord Sign sensitivity was found to be 70%, specificity 18.2%, PPV 79.5%, NPV 11.8%, and accuracy 60.7%. There was a significant relationship between Triangular Cord signs and histopathology. Gallbladder contractility parameter sensitivity was 76. %, specificity 18.2%, PPV 80.9%, NPV 14.3%, and accuracy 65.6%. However, there was no significant relationship between the histopathology results and the gallbladder wall's echogenicity, with a sensitivity of 70%, specificity of 18.2%, PPV of 79.5%, NPV of 11.8%, and accuracy of 60.7%. Conclusion:The appearance of the triangular cord sign on ultrasonography has a significant relationship with the results of histopathology in biliary atresia

Neonatal biliary atresia and vitamin D deficiency – a concern

Neonatal biliary atresia and vitamin D deficiency – a concern

Study Protocol: Design and Implementation of the Pediatric Liver Transplantation Biobank.

Background: Early treatment of neonatal biliary atresia (BA) and other end-stage liver diseases can delay or prevent the necessity of liver transplantation (LT). The establishment of a standardized clinical pediatric liver transplantation (PLT) biobank is the prerequisite for scientific research, which helps to provide a qualified sample resource platform for research. Methods: Following standardized procedures to establish biobanks, the operational processes and quality control system were formulated. Liver tissue, blood, and stool samples undergoing LT were regularly collected, managed, and stored. Systematic management was conducted in collected specimens and corresponding clinical information. Results: Since implementation in August 2018, we have enrolled 49 unique subjects (0-18 years of age); the biobank contains nearly 3000 biospecimen aliquots. The most common LT diagnosis is BA (61.23%). Conclusion: The establishment of this biobank is a valuable resource that incorporates detailed clinical and biological information. It will help accelerate the pace of PLT discovery research. ClinicalTrials.gov ID: NCT04477967.

The Role of Myeloid Populations during Perinatal Liver Injury and Repair.

Perinatal liver inflammation can have life-threatening consequences, particularly in infants and young children. An example of a hepatic inflammatory disease during infancy is biliary atresia (BA), an obliterative cholangiopathy that rapidly progresses to hepatic fibrosis and liver failure. The aggressive nature of BA in neonates compared to the pathogenesis of inflammatory liver diseases in adults, suggests that the mechanisms responsible for restoring tissue homeostasis following inflammation are impaired in affected infants. This article reviews our recent findings demonstrating that the relative abundance of Ly6cLo non-classical monocytes promotes resolution of perinatal liver injury in a murine model of perinatal hepatic inflammation. Our research also identifies a potential co-regulatory role between neutrophils and non-classical monocytes. Further work is needed to understand how neutrophils regulate other myeloid populations during perinatal liver inflammation. Elucidating the mechanisms that govern perinatal liver injury and repair may lead to the development of immune-directed therapies that can be used to mitigate the devastating effects of diseases like BA.

Successful Treatment of Pediatric Refractory Burkitt Lymphoma PTLD after Liver Transplantation using Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy

In the immunocompromised setting, recipients of solid-organ or hematopoietic stem-cell transplants carry an increased risk of post-transplant lymphoproliferative disorder (PTLD). Burkitt lymphoma (BL) PTLD is a rare form of monomorphic B-cell PTLD, which lacks a standard best treatment. Here, we report the successful treatment of refractory BL-PTLD with autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy. A male patient was diagnosed with BL-PTLD, with an increasing Epstein-Barr virus (EBV) viral load, at 21 months after undergoing living liver transplantation from his mother due to neonatal biliary atresia. After 10 cycles rituximab +/− intensive chemotherapy and surgical tumor resection, the tumors significantly advanced. Next-generation sequencing (NGS) was performed on formalin-fixed paraffin-embedded tumor tissue, revealing one mutation in exon 5, TP53: p.A159 V, which may be associated with chemo-resistance. Thus, treatment was started with autologous anti-CD19 CAR T-cell therapy. We administered 9.0 × 106/kg autologous anti-CD19 CAR T-cells, after conditioning with cyclophosphamide and fludarabine. Unexpectedly, the patient experienced only mild (Grade II) cytokine release syndrome (CRS) without neurotoxicity. Finally, he went into complete remission (CR), and has achieved 16-month event-free survival to date. In addition, liver function has remained stably within the normal range without any immunosuppressive therapy. The literature includes only five previously reported BL cases treated with CAR T-cell therapy. In conclusion, the present case suggests that autologous anti-CD19 CAR T-cell therapy may represent a new therapeutic option for some cases of refractory BL-PTLD. Clinical trial number: ChiCTR2000032211.

Incremental Value of MR Cholangiopancreatography in Diagnosis of Biliary Atresia.

PurposeTo evaluate the incremental value of a combination of magnetic resonance cholangiopancreatography (MRCP) and ultrasonography (US), compared to US alone, for diagnosing biliary atresia (BA) in neonates and young infants with cholestasis.Materials and MethodsThe institutional review board approved this retrospective study. The US and MRCP studies were both performed on 64 neonates and young infants with BA (n = 41) or without BA (non-BA) (n = 23). Two observers reviewed independently the US alone set and the combined US and MRCP set, and graded them using a five-point scale. Diagnostic performance was compared using pairwise comparison of the receiver operating characteristics (ROC) curve. The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value were assessed.ResultsThe diagnostic performance (the area under the ROC curve [Az]) for diagnosing BA improved significantly after additional review of MRCP images; Az improved from 0.688 to 0.901 (P = .015) for observer 1 and from 0.676 to 0.901 (P = .011) for observer 2. The accuracy of MRCP combined with US (observer 1, 95% [61/64]; observer 2 92% [59/64]) and PPV (observer 1, 95% [40/42]; observer 2 91% [40/44]) were significantly higher than those of US alone for both observers (accuracy: observer 1, 73% [47/64], P = 0.003; observer 2, 72% [46/64], P = 0.004; PPV: observer 1, 76% [35/46], P = 0.016; observer 2, 76% [34/45], P = 0.013). Interobserver agreement of confidence levels was good for US alone (ĸ = 0.658, P < .001) and was excellent for the combined set of US and MRCP (ĸ = 0.929, P < .001).ConclusionBetter diagnostic performance was achieved with the combination of US and MRCP than with US alone for the evaluation of BA in neonates and young infants with cholestasis.

A study to demonstrate the use of FNA cytology rather than biopsy in the diagnosis of neonatal biliary atresia

To study the use of fine needle aspiration (FNA) cytology in neonatal biliary atresia (BA). Twelve female and nine male patients (age range, 3-7months; mean age, 4.5months) with a pre-operative diagnosis of BA, who were scheduled for Kasia portoenterostomy and selected for intraoperative FNA, were studied. Cholestasis, bile deposits, bile infarcts, hepatitic rosettes enclosing bile plugs, feathery degeneration of hepatocytes and inflammatory cells were seen in the cytological slides. Bile infarcts, rosette formation and inflammatory cells were mainly noticed in type 3 BA. Bile infarcts and hepatitic rosettes are surrogate findings for the diagnosis of the obstructive type of cholestasis. With the help of imaging studies, FNA in a multidisciplinary setting can be diagnostic of neonatal BA when cytological features suggest the obstructive nature of cholestasis, but this procedure cannot replace completely liver biopsy for this diagnosis.

Biliary Atresia in Neonates and Infants

HomeRadiologyVol. 261, No. 3 PreviousNext CommunicationsLetters to the EditorBiliary Atresia in Neonates and InfantsSatheesh Krishna, Vinayak Mittal, Akshay K. Saxena, Kushaljit S. SodhiSatheesh Krishna, Vinayak Mittal, Akshay K. Saxena, Kushaljit S. SodhiAuthor AffiliationsDepartment of Radio Diagnosis, Postgraduate Institute of Medical Education and Research, Sector 12, Chandigarh 160012, India e-mail: [email protected]Satheesh KrishnaVinayak MittalAkshay K. SaxenaKushaljit S. SodhiPublished Online:Dec 1 2011https://doi.org/10.1148/radiol.11110959MoreSectionsFull textPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In Reference1 Lee MS, Kim MJ, Lee MJet al.. Biliary atresia: color Doppler US findings in neonates and infants. Radiology 2009;252(1):282–289. [Published correction appears in Radiology 2011;261(3):1003.] Link, Google ScholarArticle HistoryPublished online: Dec 2011Published in print: Dec 2011 FiguresReferencesRelatedDetailsRecommended Articles Percutaneous US-guided Cholecystocholangiography with Microbubbles for Assessment of Infants with US Findings Equivocal for Biliary Atresia and Gallbladder Longer than 1.5 cm: A Pilot StudyRadiology2017Volume: 286Issue: 3pp. 1033-1039Risk Estimation for Biliary Atresia in Patients with Neonatal Cholestasis: Development and Validation of a Risk ScoreRadiology2018Volume: 288Issue: 1pp. 262-269Hepatic Imaging in Neonates and Young Infants: State of the ArtRadiology2017Volume: 285Issue: 3pp. 763-777Pediatric Hepatic Cystic Lesions: Differential Diagnosis and Multimodality Imaging ApproachRadioGraphics2022Volume: 42Issue: 5pp. 1514-1531Insight into Bile Duct Reaction to Obstruction from a Three-dimensional Perspective Using ex Vivo Phase-Contrast CTRadiology2021Volume: 299Issue: 3pp. 597-610See More RSNA Education Exhibits Neonatal Jaundice: A Multimodality Imaging ApproachDigital Posters2018Pictorial Review of Biliary Disorders in Infants and ChildrenDigital Posters2019360 Degrees of Pediatric Biliary Disease: Multimodality Imaging ReviewDigital Posters2019 RSNA Case Collection Intrahepatic bilomaRSNA Case Collection2022Perihilar Cholangiocarcinoma RSNA Case Collection2021Perihilar CholangiocarcinomaRSNA Case Collection2021 Vol. 261, No. 3 Metrics Altmetric Score PDF download

Simple and quantitative analysis of urinary sulfated tauro- and glycodihydroxycholic acids in infant with cholestasis by electrospray ionization mass spectrometry

Here we report a simple, sensitive, and accurate method for detecting urinary sulfated tauro- and glyco-bile acids that uses electrospray ionization mass spectrometry. The sulfated tauro- and glycodihydroxycholic acids mainly generated [ M − 2H] 2− negative ions at m/ z 288.6 and m/ z 263.6, respectively. These doubly charged ions appeared primarily in samples prepared from the urine of patients with cholestasis and were detected quantitatively. Cholestatic jaundice is the primary clinical sign of biliary atresia. The measurement of doubly charged negative ions, especially of sulfated taurodihydroxycholic acid (principally taurochenodeoxycholate-3-sulfate), is a useful screening modality for biliary atresia in neonates.

Utilization of sialic acid as a coreceptor is required for reovirus-induced biliary disease.

Infection of neonatal mice with some reovirus strains produces a disease similar to infantile biliary atresia, but previous attempts to correlate reovirus infection with this disease have yielded conflicting results. We used isogenic reovirus strains T3SA- and T3SA+, which differ solely in the capacity to bind sialic acid as a coreceptor, to define the role of sialic acid in reovirus encephalitis and biliary tract infection in mice. Growth in the intestine was equivalent for both strains following peroral inoculation. However, T3SA+ spread more rapidly from the intestine to distant sites and replicated to higher titers in spleen, liver, and brain. Strikingly, mice infected with T3SA+ but not T3SA- developed steatorrhea and bilirubinemia. Liver tissue from mice infected with T3SA+ demonstrated intense inflammation focused at intrahepatic bile ducts, pathology analogous to that found in biliary atresia in humans, and high levels of T3SA+ antigen in bile duct epithelial cells. T3SA+ bound 100-fold more efficiently than T3SA- to human cholangiocarcinoma cells. These observations suggest that the carbohydrate-binding specificity of a virus can dramatically alter disease in the host and highlight the need for epidemiologic studies focusing on infection by sialic acid-binding reovirus strains as a possible contributor to the pathogenesis of neonatal biliary atresia.

Biliary atresia.

Biliary atresia.

Biliary atresia in neonates and infants: triangular area of high signal intensity in the porta hepatis at T2-weighted MR cholangiography with US and histopathologic correlation.

To correlate a triangular area of high signal intensity in the porta hepatis on T2-weighted magnetic resonance (MR) cholangiograms of biliary atresia with ultrasonographic (US) and histopathologic findings in a portal mass observed during a Kasai procedure. Twenty-one consecutive neonates and infants (age range, 13-88 days; mean age, 59 days) with cholestasis underwent US and single-shot MR cholangiography. In 12 patients with biliary atresia diagnosed at histopathologic examination, MR cholangiographic findings in the porta hepatis were correlated with US and histopathologic findings in the portal mass. At US, eight of the 12 patients had round, linear, or tubular hypoechoic portions within a triangular cord; MR cholangiography revealed a triangular area of high signal intensity confined to the porta hepatis. Histopathologic examination of the portal mass revealed a cystic or cleftlike lesion surrounded by loose myxoid mesenchyme and platelike fetal bile ducts. Neither the large cystic lesion without ductal epithelium nor the small cleftlike lesion with scanty epithelium demonstrated bile staining. Similar areas of high signal intensity were not seen on T2-weighted images in the remaining patients (four with biliary atresia and nine with neonatal hepatitis). In biliary atresia, T2-weighted single-shot MR cholangiography can show a triangular area of high signal intensity in the porta hepatis that may represent cystic dilatation of the fetal bile duct.

Choledochal cyst with or without biliary atresia in neonates and young infants: US differentiation.

To differentiate at ultrasonography (US) between the choledochal cyst associated with biliary atresia (CCBA) and that in the absence of biliary atresia (CC) in neonates and young infants. Preoperative US findings in 28 neonates and infants younger than 4 months in whom choledochal cyst was subsequently surgically confirmed were retrospectively analyzed. There was no statistically significant difference in age between the CCBA group (n = 19) and the CC group (n = 9). US findings in both groups were compared, with focus on the size of the cyst in the hepatic portal, dilatation of the intrahepatic bile ducts, and the size and morphology of the gallbladder. At US, the width and length of the cysts in the hepatic portal in the CC group were significantly larger than those in the CCBA group (P < .001). Dilatation of the intrahepatic bile ducts, seen in only one patient (5%) of the CCBA group, was observed in all patients (100%) of the CC group. The gallbladder was normal or distended in all patients of the CC group, while it was atretic or irregularly elongated in 17 patients (89%) of the CCBA group. US can be helpful in the preoperative differential diagnosis of choledochal cysts in neonates and infants. Cysts are larger, intrahepatic ducts are dilated, and gallbladders are not atretic in patients with CC as compared with those in patients with CCBA.

Rejection of murine congenic bile ducts: A model for immune-mediated bile duct disease

Immune-mediated injury of prenatal and postnatal extrahepatic bile duct epithelium has been poorly characterized. In a transplantation model of bile duct allografts, segments of the common bile duct from fetal day 18, postnatal day 7 and day 21, and adult (6-weeks) mice were grafted under the renal capsule of adult congenic mice. The progression of rejection injury in these bile duct allografts was then followed by histological evaluation at 1-week intervals. After 3 weeks there was a significant difference in the number of fetal congenic bile duct grafts that had maintained their luminal architecture compared with the more mature adult congenic grafts that had fibrosclerosed. The onset and progression of the rejection injury in the adult congenic bile duct grafts was associated with an induction of class I and class II histocompatibility antigen expression in the adult bile duct epithelium; the severity of this injury could be attenuated by treatment of the recipient mice with cyclosporin A. Thus, the fibrosclerosing lesion of extrahepatic ducts observed in this model of rejection injury is similar to the histopathology of neonatal biliary atresia or primary sclerosing cholangitis, and susceptibility to this injury is dependent on the age of the donor tissue. The immune nature of the injury and the ontogeny of expression of histocompatibility antigen in bile duct tissue indicate that the above factors may be important to the pathogenesis of these extrahepatic bile duct diseases. This experimental model may be used to test for novel factors that may modulate immune responses directed against extrahepatic bile duct epithelium.

Rapid isolation and identification of reovirus-3

Mammalian reoviruses are connected with a variety of humans diseases, including gastroenteritis, malabsorption and hepatitis. Recently, reovirus-3 was found to be associated with neonatal biliary atresia. We describe a technique for the rapid isolation and identification of reovirus-3. Mouse fibroblasts (L 929 cells) were grown in monolayers in a RPMI 1640 medium containing 10% calf serum. The cytopathic effects were visualized by the rounding of the L 929 cells and the appearance of fine granulation in the cytoplasm 48 h after the infection. Hematoxylin-eosin staining showed swelling and rounding of the infected cells, diminished chromatin in the nuclei, and the absence of mitoses. The immunohistochemical staining by the avidin-biotin-peroxidase technique was positive in the infected monolayers of the L 929 cells. The positive staining was limited to cytoplasmic inclusions, which were surrounded by a halo and sometimes by vacuoles. We conclude that the described technique is useful for the rapid isolation and identification of reovirus-3.

Biliary atresia and reovirus type 3 infection.

NEONATAL biliary atresia was originally thought to be a developmental malformation. However, microscopical examination of bile ducts resected during portoenterostomy has revealed inflammatory lesions suggesting an ongoing postnatal process such as infection.1 , 2 Viral isolation and serologic studies have usually been negative except for an occasional case associated with cytomegalovirus or congenital rubella infection.3 4 5 6 Our interest in reovirus type 3 (reo-3) as a potential cause of biliary atresia was stimulated by the observations of Stanley et al.7 They described chronic obstructive jaundice in mice, associated with choledochal obliteration that followed intraperitoneal injection of reo-3 into weanling animals.8 Although hepatic injury is . . .