title: The inflammatory phenotype of the fibrous plate is distinct from the liver and correlates with clinical outcome in biliary atresia.
abstract: Biliary atresia is an inflammatory cholangiopathy of still undetermined etiology. Correlations between histologic findings and clinical outcome in this disease have largely been based on evaluation of liver parenchyma. This study aimed to characterize the pattern of inflammation within the biliary remnant and identify associations between the type and degree of inflammation and clinical outcome as reflected by the transplant-free interval. The inflammation within the fibrous plates and livers of 41 patients with biliary atresia was characterized using immunohistochemical markers and the cell populations were digitally quantified. The type and quantity of cells within the infiltrate were then correlated with length of time from Kasai portoenterostomy until transplant. Histologic and immunohistochemical features of the biliary remnant allowed stratification of patients into "inflammatory plate" and "fibrotic plate" groups. Overall there was no significant difference in transplant-free interval between the two cohorts; however, there was a trend towards a longer time to transplant among patients in the "fibrotic plate" group. In addition, the composition of the inflammatory infiltrate in the fibrous plate was distinctly different from that present in the liver and only the characteristics of the inflammation in the fibrous plate, in particular the number of Foxp3+ T regulatory lymphocytes correlated with clinical outcome. The results of this study support the view of the extra-hepatic biliary tree as the primary site of injury in BA with the changes seen in the liver as secondary manifestations of outflow obstruction. The association between specific inflammatory cell subtypes within the fibrous plate and the length of transplant-free interval also supports the role of the immune system in the initial process of bile duct damage in biliary atresia.
authors.affiliation: Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Nicoleta C
authors.initials: NC
authors.lastname: Arva
authors.affiliation: Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, USA; Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Pierre A
authors.initials: PA
authors.lastname: Russo
authors.affiliation: Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Jessi
authors.initials: J
authors.lastname: Erlichman
authors.affiliation: Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, USA; Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Wayne W
authors.initials: WW
authors.lastname: Hancock
authors.affiliation: Merck Sharp and Dohme Corporation, North Wales, PA, USA.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Haber
authors.affiliation: Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, USA. Electronic address: bhatti@chop.edu.
authors.forename: Tricia R
authors.initials: TR
authors.lastname: Bhatti
mesh_terms: D001652:Bile Ducts / Q000473:pathology*; D001656:Biliary Atresia / Q000473:pathology* / Q000601:surgery; D005260:Female; D005355:Fibrosis / Q000473:pathology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007249:Inflammation / Q000473:pathology; D008099:Liver / Q000473:pathology*; D016031:Liver Transplantation; D008297:Male; D011379:Prognosis
keywords: Cholangiopathy; Digital image analysis; Kasai procedure; Transplant-free interval