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EBioMedicine Dec 2021Biliary Atresia is a devastating pediatric cholangiopathy affecting the bile ducts of the liver. In this review, we describe recent progress in the understanding of... (Review)
Review
Biliary Atresia is a devastating pediatric cholangiopathy affecting the bile ducts of the liver. In this review, we describe recent progress in the understanding of liver development with a focus on cholangiocyte differentiation and how use of technical platforms, including rodent, zebrafish and organoid models, advances our understanding of Biliary Atresia. This is followed by a description of potential pathomechanisms, such as autoimmune responses, inflammation, disturbed apical-basal cell polarity, primary cilia dysfunction as well as beta-amyloid accumulation. Finally, we describe current and emerging diagnostic opportunities and recent translation breakthroughs for Biliary Atresia in the area of emerging therapy development, including immunomodulation and organoid-based systems for liver and bile duct repair.
Topics: Animals; Bile Ducts; Biliary Atresia; Cell Differentiation; Disease Models, Animal; Epithelial Cells; Humans; Organoids
PubMed: 34781099
DOI: 10.1016/j.ebiom.2021.103689 -
Clinics in Liver Disease Aug 2022Biliary atresia is a rare disease but remains the most common indication for pediatric liver transplantation as there are no effective medical therapies to slow... (Review)
Review
Biliary atresia is a rare disease but remains the most common indication for pediatric liver transplantation as there are no effective medical therapies to slow progression after diagnosis. Variable contribution of genetic, immune, and environmental factors contributes to disease heterogeneity among patients with biliary atresia. Developing a deeper understanding of the disease mechanism will help to develop targeted medical therapies and improve patient outcomes.
Topics: Biliary Atresia; Child; Humans; Infant; Liver Transplantation
PubMed: 35868678
DOI: 10.1016/j.cld.2022.03.001 -
Lancet (London, England) Nov 2009Biliary atresia is a rare disease of infancy, which has changed within 30 years from being fatal to being a disorder for which effective palliative surgery or curative... (Review)
Review
Biliary atresia is a rare disease of infancy, which has changed within 30 years from being fatal to being a disorder for which effective palliative surgery or curative liver transplantation, or both, are available. Good outcomes for infants depend on early referral and timely Kasai portoenterostomy, and thus a high index of suspicion is needed for investigation of infants with persistent jaundice. In centres with much experience of treating this disorder, up to 60% of children will achieve biliary drainage after Kasai portoenterostomy and will have serum bilirubin within the normal range within 6 months. 80% of children who attain satisfactory biliary drainage will reach adolescence with a good quality of life without undergoing liver transplantation. Although much is known about management of biliary atresia, many aspects are poorly understood, including its pathogenesis. Several hypotheses exist, implicating genetic predisposition and dysregulation of immunity, but the cause is probably multifactorial, with obliterative extrahepatic cholangiopathy as the common endpoint. Researchers are focused on identification of relevant genetic and immune factors and understanding serum and hepatic factors that drive liver fibrosis after Kasai portoenterostomy. These factors might become therapeutic targets to halt the inevitable development of cirrhosis and need for liver transplantation.
Topics: Abnormalities, Multiple; Algorithms; Biliary Atresia; Diagnosis, Differential; Disease Progression; Early Diagnosis; Genetic Predisposition to Disease; Humans; Infant, Newborn; Jaundice, Neonatal; Liver Transplantation; Neonatal Screening; Palliative Care; Patient Selection; Portoenterostomy, Hepatic; Prognosis; Rare Diseases; Referral and Consultation; Risk Factors; Treatment Outcome
PubMed: 19914515
DOI: 10.1016/S0140-6736(09)60946-6 -
Journal of Autoimmunity Sep 2016Biliary atresia presents as an obliterative cholangiopathy with neonatal jaundice and pale stools. The disease exhibits aetiological heterogeneity with a multiplicity of... (Review)
Review
Biliary atresia presents as an obliterative cholangiopathy with neonatal jaundice and pale stools. The disease exhibits aetiological heterogeneity with a multiplicity of potential causative factors, both developmental and environmental. A number of clinical variants making up a minority of all cases can be defined relatively precisely which match suggested aetiology better although in most it still remains speculative. These include the syndromic form (BASM), the cystic form and those associated with CMV IgM antibodies. We review not only the clinical evidence for a developmental or an immune-mediated aetiology perhaps triggered by perinatal viral exposure but also several other recently suggested concepts such as microchimerism, gene susceptibility and environmental toxins.
Topics: Bile Ducts; Biliary Atresia; Biopsy; Chimerism; Cytomegalovirus; Environmental Exposure; Genetic Predisposition to Disease; Humans; Immunity, Humoral; Immunoglobulin M; Incidence; Infant; Liver; Liver Function Tests; T-Lymphocytes; Ultrasonography
PubMed: 27346637
DOI: 10.1016/j.jaut.2016.06.005 -
Pediatric Radiology Apr 2022Biliary atresia is challenging to diagnose because many of the clinical and imaging features of this condition overlap with those of other causes of cholestasis in... (Review)
Review
Biliary atresia is challenging to diagnose because many of the clinical and imaging features of this condition overlap with those of other causes of cholestasis in newborns. When jaundice persists beyond 2 weeks of age, the neonate should be evaluated for cholestasis, and biliary atresia - the most common cause of neonatal cholestasis - should be considered. It is critical to diagnose biliary atresia early because failure to treat can result in hepatic fibrosis and death in less than 1 year. In this paper, we review the current diagnostic imaging methods, differential considerations and treatment options for biliary atresia.
Topics: Biliary Atresia; Cholestasis; Diagnosis, Differential; Humans; Infant; Infant, Newborn
PubMed: 34331566
DOI: 10.1007/s00247-021-05148-y -
Hepatology (Baltimore, Md.) Sep 2018Biliary atresia (BA) is a fibroinflammatory disease of the intrahepatic and extrahepatic biliary tree. Surgical hepatic portoenterostomy (HPE) may restore bile drainage,... (Review)
Review
Biliary atresia (BA) is a fibroinflammatory disease of the intrahepatic and extrahepatic biliary tree. Surgical hepatic portoenterostomy (HPE) may restore bile drainage, but progression of the intrahepatic disease results in complications of portal hypertension and advanced cirrhosis in most children. Recognizing that further progress in the field is unlikely without a better understanding of the underlying cause(s) and pathogenesis of the disease, the National Institutes of Diabetes and Digestive and Kidney Diseases (NIDDK) sponsored a research workshop focused on innovative and promising approaches and on identifying future areas of research. Investigators discussed recent advances using gestational ultrasound and results of newborn BA screening with serum direct (conjugated) bilirubin that support a prenatal onset of biliary injury. Experimental and human studies implicate the toxic properties of environmental toxins (e.g., biliatresone) and of viruses (e.g., cytomegalovirus) to the biliary system. Among host factors, sequence variants in genes related to biliary development and ciliopathies, a notable lack of a cholangiocyte glycocalyx and of submucosal collagen bundles in the neonatal extrahepatic bile ducts, and an innate proinflammatory bias of the neonatal immune system contribute to an increased susceptibility to damage and obstruction following epithelial injury. These advances form the foundation for a future research agenda focused on identifying the environmental and host factor(s) that cause BA, the potential use of population screening, studies of the mechanisms of prominent fibrosis in young infants, determinations of clinical surrogates of disease progression, and the design of clinical trials that target subgroups of patients with initial drainage following HPE. (Hepatology 2018; 00:000-000).
Topics: Biliary Atresia; Humans; Infant, Newborn
PubMed: 29604222
DOI: 10.1002/hep.29905 -
Seminars in Pediatric Surgery Aug 2020Biliary atresia (BA) is a common cause of surgical jaundice during the neonatal period. It is currently considered as a spectrum of diseases with a common final... (Review)
Review
Biliary atresia (BA) is a common cause of surgical jaundice during the neonatal period. It is currently considered as a spectrum of diseases with a common final pathology characterized by obliteration of the extrahepatic biliary tract and the absence of normally branching intrahepatic ducts. Though it is a global disease that can be found in all ethnicities there are some clear differences between BA arising in the East and the West. This is likely to be related to different genetic, environmental and cultural factors. BA is more frequently found in Far Eastern infants (both Chinese and Japanese) though the syndromic associations are much less common. Many Eastern countries have national screening programmes not seen in the West possibly due to debate over its cost effectiveness in countries where incidence is low. Kasai portoenterostomy (KPE) is considered as the primary treatment of BA but its outcome still remains unsatisfactory across the region. Given the complexity of BA, it is unlikely that strategic advances could be made by the sole effort of individual countries and we believe that collaboration between the East and West is the way forward.
Topics: Biliary Atresia; Humans; Infant, Newborn; Infant, Newborn, Diseases; Liver Transplantation; Portoenterostomy, Hepatic
PubMed: 32861448
DOI: 10.1016/j.sempedsurg.2020.150950 -
Pediatrics in Review Nov 2022
Topics: Humans; Infant; Biliary Atresia
PubMed: 36316259
DOI: 10.1542/pir.2021-005287 -
Mayo Clinic Proceedings Jan 1998Extrahepatic biliary atresia is an obliterative cholangiopathy that involves all or part of the extrahepatic biliary tree and, in many cases, the intrahepatic bile... (Review)
Review
Extrahepatic biliary atresia is an obliterative cholangiopathy that involves all or part of the extrahepatic biliary tree and, in many cases, the intrahepatic bile ducts. In the United States, from 400 to 600 new cases of biliary atresia are encountered annually. The diagnosis is usually suggested by the persistence of jaundice for 6 weeks or more after birth. Several factors have been considered for the pathogenesis of extrahepatic biliary atresia, including viral infection, metabolic insults, and abnormalities in bile duct morphogenesis. Although selected patients benefit from prompt diagnosis and Kasai portoenterostomy surgical intervention within the first 60 days of life, many ultimately require liver transplantation because of portal hypertension, recurrent cholangitis, and cirrhosis.
Topics: Bile Ducts, Extrahepatic; Biliary Atresia; Diagnosis, Differential; Humans; Liver
PubMed: 9443685
DOI: 10.1016/S0025-6196(11)63625-2 -
Seminars in Pediatric Surgery May 1992Although biliary atresia is characterized by luminal obstruction of the extrahepatic bile ducts, the etiology and the pathophysiology of the liver are still... (Review)
Review
Although biliary atresia is characterized by luminal obstruction of the extrahepatic bile ducts, the etiology and the pathophysiology of the liver are still controversial. The prognosis of biliary atresia has been improved after the introduction of Kasai's hepatic portoenterostomy, but there are still many problems to be solved in the treatment of this disease. Successful results of hepatic portoenterostomy depend on early diagnosis and operation, adequate operative technique, prevention of postoperative cholangitis, and precise postoperative management. However, we are on the verge of a new era in the therapy of biliary atresia combining portoenterostomy with liver transplantation.
Topics: Biliary Atresia; Child; Child, Preschool; Humans; Infant; Infant, Newborn; Portoenterostomy, Hepatic
PubMed: 1345477
DOI: No ID Found