title: Pathogenesis of biliary atresia: defining biology to understand clinical phenotypes.
abstract: Biliary atresia is a severe cholangiopathy of early infancy that destroys extrahepatic bile ducts and disrupts bile flow. With a poorly defined disease pathogenesis, treatment consists of the surgical removal of duct remnants followed by hepatoportoenterostomy. Although this approach can improve the short-term outcome, the liver disease progresses to end-stage cirrhosis in most children. Further improvement in outcome will require a greater understanding of the mechanisms of biliary injury and fibrosis. Here, we review progress in the field, which has been fuelled by collaborative studies in larger patient cohorts and the development of cell culture and animal model systems to directly test hypotheses. Advances include the identification of phenotypic subgroups and stages of disease based on clinical, pathological and molecular features. Stronger evidence exists for viruses, toxins and gene sequence variations in the aetiology of biliary atresia, triggering a proinflammatory response that injures the duct epithelium and produces a rapidly progressive cholangiopathy. The immune response also activates the expression of type 2 cytokines that promote epithelial cell proliferation and extracellular matrix production by nonparenchymal cells. These advances provide insight into phenotype variability and might be relevant to the design of personalized trials to block progression of liver disease.
authors.affiliation: Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Asai
authors.affiliation: Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Miethke
authors.affiliation: Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA.
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Bezerra
mesh_terms: D000818:Animals; D001656:Biliary Atresia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D007223:Infant; D007231:Infant, Newborn
chemical_list: D016207:Cytokines