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Mark Davenport - One of the best experts on this subject based on the ideXlab platform.
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cytomegalovirus associated Biliary Atresia an aetiological and prognostic subgroup
Journal of Pediatric Surgery, 2015Co-Authors: Augusto Zani, Alberto Quaglia, Nedim Hadzic, Mark Zuckerman, Mark DavenportAbstract:Abstract Background and aims Perinatal cytomegalovirus (CMV) infection is a possible cause or trigger of Biliary Atresia though clinical evidence is scant. We hypothesised that CMV IgM+ve Biliary Atresia is a separate clinical entity compared to CMV IgM−ve Biliary Atresia. Methods Prospective single-centre study. 210 infants with histologically confirmed Biliary Atresia were treated in our institution (Jan. 2004 to Dec. 2011); of these 20 (9.5%) were CMV IgM+ve at presentation. We compared these with 111 infants who were CMV IgM−ve (controls) for clinical features, biochemistry at presentation and outcome following Kasai portoenterostomy (KPE). A blinded comparison of age-matched liver histology was also performed. Data are quoted as median (interquartile range). A P value ≤0.05 was regarded as significant. Results Infants with CMV IgM+ve Biliary Atresia were older at Kasai portoenterostomy (or laparotomy) [70 (60–80) days vs. 56 (44–75)days; P=0.003] and were more jaundiced [175 (147–224) vs. 140 (121–181) μmol/L; P=0.002+ with higher AST*287 (157–403) vs. 180 (133–254) IU/L; P=0.005] and aspartate aminotransferase-to-platelet ratio index [1.1 (0.79–3.0) vs. 0.63 (0.43–0.95)] levels. Liver histology : CMV IgM+ve Biliary Atresia was characterised by a greater degree of inflammation (P Outcome : CMV IgM+ve Biliary Atresia had a poorer outcome with a reduced clearance of jaundice (15% vs. 52.2%; P=0.002), native liver survival (P Conclusions CMV IgM+ve Biliary Atresia is a distinct clinical and pathological entity with a diminished response to Kasai portoenterostomy.
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E39 Biliary Atresia
Basic Techniques in Pediatric Surgery, 2013Co-Authors: Mark DavenportAbstract:Biliary Atresia (BA) is of essentially unknown origin, though there are several definable types. Most are isolated BA, but about 10 % will have features of Biliary Atresia splenic malformation syndrome (e.g. polysplenia, situs inversus, preduodenal portal vein, absence of the vena cava, malrotation, etc.). Other variants include cystic BA (which may contain bile or mucus and are not simply obstructed choledochal cysts) and Cytomegalovirus-associated BA.
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epidemiology of Biliary Atresia in england and wales 1999 2006
Archives of Disease in Childhood-fetal and Neonatal Edition, 2009Co-Authors: Emily Livesey, Nedim Hadzic, Deirdre Kelly, Khalid Sharif, Naved K. Alizai, Patricia Mcclean, Cortina M Borja, Mark DavenportAbstract:Objective: To identify the epidemiological characteristics of infants with Biliary Atresia in England and Wales, since centralisation of its management in 1999. Methods: The care of infants with Biliary Atresia (BA) in England and Wales is centralised to only three centres. All infants (treated from January 1999 to December 2006) were identified from a prospective national database; demographic details were ascertained from medical records and compared between two groups based on presumed aetiology (isolated Biliary Atresia (IBA) and developmental Biliary Atresia (DBA) (for example, syndromic infants, Biliary Atresia splenic malformation, cystic Biliary Atresia)). Results: There were 302 (133 male (44%)) infants with BA that could be divided into IBA (n = 219, 73%) and DBA (n = 76, 25%). The overall incidence was 0.58/10 000 (1 in 17 049) live births with marked regional differences along a north-west/south-east axis varying from 0.38 (north-west England) to 0.78 (south-east England)/10 000 live births (OR 2.05 (95% CI 1.26–3.41); p = 0.002). The commonest month of birth was September with December being the least common, although there was no evidence for significant seasonal variation (p = 0.2). Infants with DBA were more likely to be female (p Conclusions: There is a remarkable variation of incidence of Biliary Atresia within England and Wales, some of which may have been caused by factors related to a different aetiological and racial background.
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Epidemiology of Biliary Atresia in England and Wales (1999–2006)
Archives of disease in childhood. Fetal and neonatal edition, 2009Co-Authors: Emily Livesey, Nedim Hadzic, Deirdre Kelly, M Cortina Borja, Khalid Sharif, Naved K. Alizai, Patricia Mcclean, Mark DavenportAbstract:Objective: To identify the epidemiological characteristics of infants with Biliary Atresia in England and Wales, since centralisation of its management in 1999. Methods: The care of infants with Biliary Atresia (BA) in England and Wales is centralised to only three centres. All infants (treated from January 1999 to December 2006) were identified from a prospective national database; demographic details were ascertained from medical records and compared between two groups based on presumed aetiology (isolated Biliary Atresia (IBA) and developmental Biliary Atresia (DBA) (for example, syndromic infants, Biliary Atresia splenic malformation, cystic Biliary Atresia)). Results: There were 302 (133 male (44%)) infants with BA that could be divided into IBA (n = 219, 73%) and DBA (n = 76, 25%). The overall incidence was 0.58/10 000 (1 in 17 049) live births with marked regional differences along a north-west/south-east axis varying from 0.38 (north-west England) to 0.78 (south-east England)/10 000 live births (OR 2.05 (95% CI 1.26–3.41); p = 0.002). The commonest month of birth was September with December being the least common, although there was no evidence for significant seasonal variation (p = 0.2). Infants with DBA were more likely to be female (p Conclusions: There is a remarkable variation of incidence of Biliary Atresia within England and Wales, some of which may have been caused by factors related to a different aetiological and racial background.
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Acquired Biliary Atresia
Journal of pediatric surgery, 1996Co-Authors: Mark Davenport, R. Saxena, Edward R. HowardAbstract:Three infants are described in whom acquired Biliary Atresia developed during the perinatal period. In two cases this was related to a spontaneous perforation of the bile duct, and in the other it probably was related to previous surgery for duodenal and ileal Atresias. Clinically, the symptoms in these patients differed from the congenital forms of Biliary Atresia; two of the infants had dilated intrahepatic ducts on ultrasonography, and all had restriction of disease to the extrahepatic bile ducts and an excellent response to surgery.
Kasper S. Wang - One of the best experts on this subject based on the ideXlab platform.
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Newborn Screening for Biliary Atresia
Pediatrics, 2015Co-Authors: Kasper S. WangAbstract:Biliary Atresia is the most common cause of pediatric end-stage liver disease and the leading indication for pediatric liver transplantation. Affected infants exhibit evidence of Biliary obstruction within the first few weeks after birth. Early diagnosis and successful surgical drainage of bile are associated with greater survival with the child's native liver. Unfortunately, because noncholestatic jaundice is extremely common in early infancy, it is difficult to identify the rare infant with cholestatic jaundice who has Biliary Atresia. Hence, the need for timely diagnosis of this disease warrants a discussion of the feasibility of screening for Biliary Atresia to improve outcomes. Herein, newborn screening for Biliary Atresia in the United States is assessed by using criteria established by the Discretionary Advisory Committee on Heritable Disorders in Newborns and Children. Published analyses indicate that newborn screening for Biliary Atresia by using serum bilirubin concentrations or stool color cards is potentially life-saving and cost-effective. Further studies are necessary to evaluate the feasibility, effectiveness, and costs of potential screening strategies for early identification of Biliary Atresia in the United States.
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Recent Advances in the Pathogenesis and Management of Biliary Atresia
Current opinion in pediatrics, 2015Co-Authors: Jessica A. Zagory, Marie V. Nguyen, Kasper S. WangAbstract:The purpose of this study is to review advances in both the pathogenesis and clinical management of Biliary Atresia. Immunologic studies have further characterized roles of helper T-cells, B-cells, and natural killer cells in the immune dysregulation following viral replication within and damage of Biliary epithelium. Prominin-1-expressing portal fibroblasts may play an integral role in the Biliary fibrosis associated with Biliary Atresia. A number of genetic polymorphisms have been characterized as leading to susceptibility for Biliary Atresia. Postoperative corticosteroid therapy is not associated with greater transplant-free survival. Newborn screening may improve outcomes of infants with Biliary Atresia and may also provide a long-term cost benefit. Although recent advances have enhanced our understanding of pathogenesis and clinical management, Biliary Atresia remains a significant challenge requiring further investigation.
Folkert O. Belzer - One of the best experts on this subject based on the ideXlab platform.
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Long-term results of liver transplantation for Biliary Atresia.
Surgery, 1993Co-Authors: Munci Kalayoglu, Angelo D'alessandro, Stuart J. Knechtle, Devin E. Eckhoff, John D. Pirsch, Robert H. Judd, H. W. Sollinger, Robert M. Hoffmann, Folkert O. BelzerAbstract:Biliary Atresia can be treated by portoenterostomy, which is primarily palliative, or by liver transplantation, which is primarily curative. The purpose of this study was to determine the long-term outcome of liver transplantation for the treatment of Biliary Atresia. During an 8-year period, 45 patients who underwent liver transplantation for Biliary Atresia and 10 patients who were referred to our center for portoenterostomy were retrospectively analyzed. No patient with Biliary Atresia died awaiting liver transplantation. The waiting time for all patients was 36.7 +/- 42.8 days. Thirty-four patients (75.6%) required one transplant, whereas 11 patients (24.4%) required 17 retransplants. Twenty-two patients (48.9%) required 39 reoperations (1.8 per patient). There were 4.9 infectious episodes, 2.2 rejection episodes, and 4.4 readmissions per patient. However, 91% of reoperations, 80% of infections, and 78% of rejections occurred within 6 months of transplantation. The overall 7-year actuarial patient and graft survival for patients with Biliary Atresia was 86.2% and 62.7%, respectively. Our results indicate that long-term patient survival after liver transplantation for Biliary Atresia is excellent. However, portoenterostomy continues to have an initial complementary but limited long-term role in the treatment of infants with Biliary Atresia.
Emily Livesey - One of the best experts on this subject based on the ideXlab platform.
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epidemiology of Biliary Atresia in england and wales 1999 2006
Archives of Disease in Childhood-fetal and Neonatal Edition, 2009Co-Authors: Emily Livesey, Nedim Hadzic, Deirdre Kelly, Khalid Sharif, Naved K. Alizai, Patricia Mcclean, Cortina M Borja, Mark DavenportAbstract:Objective: To identify the epidemiological characteristics of infants with Biliary Atresia in England and Wales, since centralisation of its management in 1999. Methods: The care of infants with Biliary Atresia (BA) in England and Wales is centralised to only three centres. All infants (treated from January 1999 to December 2006) were identified from a prospective national database; demographic details were ascertained from medical records and compared between two groups based on presumed aetiology (isolated Biliary Atresia (IBA) and developmental Biliary Atresia (DBA) (for example, syndromic infants, Biliary Atresia splenic malformation, cystic Biliary Atresia)). Results: There were 302 (133 male (44%)) infants with BA that could be divided into IBA (n = 219, 73%) and DBA (n = 76, 25%). The overall incidence was 0.58/10 000 (1 in 17 049) live births with marked regional differences along a north-west/south-east axis varying from 0.38 (north-west England) to 0.78 (south-east England)/10 000 live births (OR 2.05 (95% CI 1.26–3.41); p = 0.002). The commonest month of birth was September with December being the least common, although there was no evidence for significant seasonal variation (p = 0.2). Infants with DBA were more likely to be female (p Conclusions: There is a remarkable variation of incidence of Biliary Atresia within England and Wales, some of which may have been caused by factors related to a different aetiological and racial background.
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Epidemiology of Biliary Atresia in England and Wales (1999–2006)
Archives of disease in childhood. Fetal and neonatal edition, 2009Co-Authors: Emily Livesey, Nedim Hadzic, Deirdre Kelly, M Cortina Borja, Khalid Sharif, Naved K. Alizai, Patricia Mcclean, Mark DavenportAbstract:Objective: To identify the epidemiological characteristics of infants with Biliary Atresia in England and Wales, since centralisation of its management in 1999. Methods: The care of infants with Biliary Atresia (BA) in England and Wales is centralised to only three centres. All infants (treated from January 1999 to December 2006) were identified from a prospective national database; demographic details were ascertained from medical records and compared between two groups based on presumed aetiology (isolated Biliary Atresia (IBA) and developmental Biliary Atresia (DBA) (for example, syndromic infants, Biliary Atresia splenic malformation, cystic Biliary Atresia)). Results: There were 302 (133 male (44%)) infants with BA that could be divided into IBA (n = 219, 73%) and DBA (n = 76, 25%). The overall incidence was 0.58/10 000 (1 in 17 049) live births with marked regional differences along a north-west/south-east axis varying from 0.38 (north-west England) to 0.78 (south-east England)/10 000 live births (OR 2.05 (95% CI 1.26–3.41); p = 0.002). The commonest month of birth was September with December being the least common, although there was no evidence for significant seasonal variation (p = 0.2). Infants with DBA were more likely to be female (p Conclusions: There is a remarkable variation of incidence of Biliary Atresia within England and Wales, some of which may have been caused by factors related to a different aetiological and racial background.
Cara L. Mack - One of the best experts on this subject based on the ideXlab platform.
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Update on investigations pertaining to the pathogenesis of Biliary Atresia.
Pediatric surgery international, 2017Co-Authors: Alexandra Kilgore, Cara L. MackAbstract:Biliary Atresia is a devastating Biliary disease of neonates that results in liver transplantation for the vast majority. The etiology of Biliary Atresia is unknown and is likely multifactorial, with components of genetic predisposition, environmental trigger and autoimmunity contributing to disease pathogenesis. This review highlights recent work related to investigations of disease pathogenesis in Biliary Atresia.
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Biliary Atresia: Clinical Lessons Learned.
Journal of pediatric gastroenterology and nutrition, 2015Co-Authors: Amy G. Feldman, Cara L. MackAbstract:Biliary Atresia is a rare disease of unclear etiology, in which obstruction of the Biliary tree causes severe cholestasis leading to cirrhosis and ultimately death if left untreated. Biliary Atresia is the leading cause of neonatal cholestasis and the most frequent indication for pediatric liver transplantation. Any infant with persistent jaundice beyond 2 weeks of life needs to be evaluated for Biliary Atresia with fractionation of the bilirubin into conjugated and unconjugated portions. Early performance of a hepatoportoenterostomy in the first 45 days of life to restore bile flow and lessen further damage to the liver is thought to optimize outcome. Despite surgery, progressive liver scarring occurs, and 80% of patients with Biliary Atresia will require liver transplantation during childhood.
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Expression of osteopontin correlates with portal Biliary proliferation and fibrosis in Biliary Atresia.
Pediatric research, 2005Co-Authors: Peter F Whitington, Cara L. Mack, Padmini Malladi, Hector Melin-aldana, Ruba Azzam, Atul SahaiAbstract:The acquired or perinatal form of Biliary Atresia is a Th1 fibro-inflammatory disease affecting both the extrahepatic and intrahepatic bile ducts. Osteopontin (OPN) is a Th1 cytokine implicated in several fibro-inflammatory and autoimmune diseases. We examined the expression of OPN in acquired Biliary Atresia in comparison to normal liver and several pediatric cholestatic liver diseases. We also assessed OPN expression by cultured human bile duct epithelial cells. We found that liver OPN mRNA and protein expression were significantly increased in Biliary Atresia versus normal and other cholestatic diseases. OPN expression in Biliary Atresia was localized to epithelium of proliferating Biliary structures (ductules and/or ducts) and bile plugs contained therein. No portal Biliary OPN expression could be demonstrated in normal liver, syndromic Biliary Atresia, Biliary obstruction not due to Biliary Atresia, and idiopathic neonatal hepatitis. OPN expression by human bile duct epithelial cells in culture was responsive to IL-2 and TNF-alpha. Our results demonstrate an up-regulation of OPN expression by interlobular Biliary epithelium in Biliary Atresia, which correlates with Biliary proliferation and portal fibrosis. These findings suggest a role for OPN in the pathogenesis of Biliary Atresia.
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Biliary Atresia is associated with cd4 th1 cell mediated portal tract inflammation
Pediatric Research, 2004Co-Authors: Cara L. Mack, Ronald J. Sokol, Frederick M Karrer, Rebecca M Tucker, Brian L Kotzin, Peter F Whitington, Stephen D MillerAbstract:A proposed mechanism in the pathogenesis of Biliary Atresia involves an initial virus-induced, progressive T cell–mediated inflammatory obliteration of bile ducts. The aim of this study was to characterize the inflammatory environment present within the liver of infants with Biliary Atresia to gain insight into the role of a primary immune-mediated process versus a nonspecific secondary response to Biliary obstruction. Frozen liver tissue obtained from patients with Biliary Atresia, neonatal giant cell hepatitis, total parenteral nutrition (TPN)–related cholestasis, choledochal cysts, and normal control subjects was used for fluorescent immunohistochemistry studies of cellular infiltrates, cytokine mRNA expression, and in situ hybridization for localization of cytokine-producing cells. Immunohistochemistry revealed increases in CD8+ and CD4+ T cells and Kupffer cells (CD68+) in the portal tracts of Biliary Atresia. Reverse transcription–PCR analysis of Biliary Atresia tissue showed a Th1-type cytokine profile with expression of IL-2, interferon-γ, tumor necrosis factor-α, and IL-12. This profile was not seen in normal, neonatal hepatitis or choledochal cyst livers but was present in TPN-related cholestasis. In situ hybridization revealed that the Th1 cytokine–producing cells were located in the portal tracts in Biliary Atresia and in the parenchyma of TPN-related cholestasis. A distinctive portal tract inflammatory environment is present in Biliary Atresia, involving CD4+ Th1 cell–mediated immunity. The absence of similar inflammation in other pediatric cholestatic conditions suggests that the portal tract inflammation in Biliary Atresia is not a secondary response to cholestasis but rather indicates a specific immune response involved in the pathogenesis of Biliary Atresia.
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pathogenesis and outcome of Biliary Atresia current concepts
Journal of Pediatric Gastroenterology and Nutrition, 2003Co-Authors: Ronald J. Sokol, Cara L. Mack, Michael R Narkewicz, Frederick M KarrerAbstract:Neonatal cholestatic disorders are a group of hepatoBiliary diseases occurring within the first 3 months of life. Bile flow is impaired, and patients have conjugated hyperbilirubinemia, acholic stools, and hepatomegaly. Overall, 1 in 2,500 live births is affected with a neonatal cholestatic disorder (1). The two most common causes of neonatal cholestasis are Biliary Atresia and idiopathic neonatal hepatitis, accounting for up to 50% to 70% of cases. Other causes include a variety of neonatal infections (viral, toxoplasmosis, syphilis, bacterial), metabolic and genetic diseases, progressive familial intrahepatic cholestatic disorders (PFIC), paucity of interlobular bile duct disorders (e.g., Alagille syndrome), choledochal cyst, ischemia–reperfusion injury, association with parenteral nutrition administration, and other conditions (Table 1). Despite clinical improvement after the portoenterostomy procedure, approximately 70% to 80% of children with Biliary Atresia will eventually require liver transplantation; thus, Biliary Atresia alone accounts for almost 50% of all liver transplants performed in children (1). It should be noted that $77 million is spent each year in the United States on liver transplantation for children and the ensuing hospitalizations (2). This sum of money covers 0.2% of total health care expenditures related to children, even though these children represent 0.0006% of the total pediatric population. Importantly, this disproportionate expenditure for liver transplantation in children could be cut in half if improved therapies for Biliary Atresia were developed that could abrogate or further delay the need for liver transplantation. Remarkably, little is known about the etiopathogenesis of Biliary Atresia; consequently, there has been slow progress in developing improved therapies or preventative strategies during the past decade. The purpose of this review is to summarize recent advances in the diagnosis and management of Biliary Atresia, examine the clinical outcome, describe the evolving theories of the etiology and pathogenesis of this disorder, and highlight gaps in our current knowledge.