title: Staging of biliary atresia at diagnosis by molecular profiling of the liver.
abstract: BACKGROUND
  Young age at portoenterostomy has been linked to improved outcome in biliary atresia, but pre-existing biological factors may influence the rate of disease progression. In this study, we aimed to determine whether molecular profiling of the liver identifies stages of disease at diagnosis.
  
  
  METHODS
  We examined liver biopsies from 47 infants with biliary atresia enrolled in a prospective observational study. Biopsies were scored for inflammation and fibrosis, used for gene expression profiles, and tested for association with indicators of disease severity, response to surgery, and survival at 2 years.
  
  
  RESULTS
  Fourteen of 47 livers displayed predominant histological features of inflammation (N = 9) or fibrosis (N = 5), with the remainder showing similar levels of both simultaneously. By differential profiling of gene expression, the 14 livers had a unique molecular signature containing 150 gene probes. Applying prediction analysis models, the probes classified 29 of the remaining 33 livers into inflammation or fibrosis. Molecular classification into the two groups was validated by the findings of increased hepatic population of lymphocyte subsets or tissue accumulation of matrix substrates. The groups had no association with traditional markers of liver injury or function, response to surgery, or complications of cirrhosis. However, infants with an inflammation signature were younger, while those with a fibrosis signature had decreased transplant-free survival.
  
  
  CONCLUSIONS
  Molecular profiling at diagnosis of biliary atresia uncovers a signature of inflammation or fibrosis in most livers. This signature may relate to staging of disease at diagnosis and has implications to clinical outcomes.
authors.affiliation: Division of Pediatric Gastroenterology, Hepatology and Nutrition of Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA. katie.moyer@cchmc.org.
authors.forename: Katie
authors.initials: K
authors.lastname: Moyer
authors.forename: Vivek
authors.initials: V
authors.lastname: Kaimal
authors.forename: Cristina
authors.initials: C
authors.lastname: Pacheco
authors.forename: Reena
authors.initials: R
authors.lastname: Mourya
authors.forename: Huan
authors.initials: H
authors.lastname: Xu
authors.forename: Pranavkumar
authors.initials: P
authors.lastname: Shivakumar
authors.forename: Ranajit
authors.initials: R
authors.lastname: Chakraborty
authors.forename: Marepalli
authors.initials: M
authors.lastname: Rao
authors.forename: John C
authors.initials: JC
authors.lastname: Magee
authors.forename: Kevin
authors.initials: K
authors.lastname: Bove
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Aronow
authors.forename: Anil G
authors.initials: AG
authors.lastname: Jegga
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Bezerra
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