title: Native liver histology after successful portoenterostomy in biliary atresia.
abstract: BACKGROUND
  Biliary atresia is the most common indication for childhood liver transplantation. The effects of successful portoenterostomy (PE) on native liver histology remain unclear.
  
  
  OBJECTIVE
  We assessed changes in native liver histology after a successful PE in relation to liver function and clinical outcomes.
  
  
  METHODS
  In total, 70 native liver biopsies of 44 biliary atresia patients were obtained at PE (n=30), 4.2 years after successful PE (n=23) and 1.1 years after failed PE (n=17), and reviewed for cholestasis, fibrosis, inflammation, and cytokeratin 7 (CK7) immunopositivity (chronic cholestasis). Ten transplant donor livers served as controls.
  
  
  RESULTS
  After a successful PE [serum bilirubin 11 (2 to 35) μmol/L at biopsy], histologic native liver cholestasis completely resolved in 83% of the patients and portal inflammation significantly decreased. Nevertheless, enhanced fibrosis [Metavir stage 2 (1-4) vs. 4 (1-4)], bile duct proliferation [grade 2 (1-2) vs. 1 (0-2)], and periportal CK7 immunostaining [grade 1 (0-2) vs. 1 (0-4)] persisted in 100%, 87%, and 61% of subjects, respectively. Metavir fibrosis stage corresponded cirrhosis (stage 4) in 52% of the patients, associated with the presence of portal hypertension, and correlated with serum-conjugated bilirubin (r=0.601, P=0.002), bile duct proliferation (r=0.657, P=0.001), and CK7 positivity (r=0.657, P=0.001). Aspartate transferase to platelet ratio index predicted native liver fibrosis and development of esophageal varices. The degree of fibrosis and portal inflammation at PE were unrelated to native liver survival.
  
  
  CONCLUSIONS
  Despite resolution of cholestasis and decreasing inflammation, bile duct proliferation, periportal CK7 immunostaining, and fibrosis persist after successful PE. Fibrosis is associated with biochemical cholestasis, bile duct proliferation, CK7 immunopositivity (chronic cholestasis), and development of portal hypertension.
authors.affiliation: Departments of *Pediatric Surgery §Pediatric Nephrology and Transplantation, Children's Hospital ‡Department of Pathology, HUSLAB, Helsinki University Central Hospital †National Graduate School of Clinical Investigation, Helsinki, Finland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Lampela
authors.forename: Silja
authors.initials: S
authors.lastname: Kosola
authors.forename: Päivi
authors.initials: P
authors.lastname: Heikkilä
authors.forename: Jouko
authors.initials: J
authors.lastname: Lohi
authors.forename: Hannu
authors.initials: H
authors.lastname: Jalanko
authors.forename: Mikko P
authors.initials: MP
authors.lastname: Pakarinen
mesh_terms: D000293:Adolescent; D001656:Biliary Atresia / Q000601:surgery*; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D002779:Cholestasis / Q000453:epidemiology / Q000473:pathology; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007249:Inflammation / Q000453:epidemiology / Q000473:pathology; D053552:Keratin-7 / Q000276:immunology; D008103:Liver Cirrhosis / Q000453:epidemiology / Q000473:pathology; D008107:Liver Diseases / Q000453:epidemiology / Q000473:pathology*; D008111:Liver Function Tests; D011171:Portoenterostomy, Hepatic / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D053552:Keratin-7