title: APRi predicts native liver survival by reflecting portal fibrogenesis and hepatic neovascularization at the time of portoenterostomy in biliary atresia.
abstract: BACKGROUND
  Aspartate aminotransferase-to-platelet ratio index (APRi) may be useful noninvasive prognostic tool in biliary atresia (BA). We studied whether APRi predicts native liver survival and parallels biochemical and immunohistological signs of liver injury and fibrogenesis at the time of Kasai portoenterostomy (PE).
  
  
  METHODS
  Serum and liver specimens were obtained at PE from 29 BA patients for liver biochemistry including APRi, histology and immunohistochemical analysis of collagen 1, α-SMA and CD34. APRi values were related to native liver survival and other clinical data as well as serum liver biochemistry, liver histology and immunohistochemistry at PE.
  
  
  RESULTS
  Median age at PE was 63 (range 7-141) days and median APRi was 0.92 (0.13-6.39). APRi had strong positive correlations with patient age (r=0.684, p<0.001) and biochemical signs of hepatocyte injury and cholestasis. APRi showed no significant correlations with Metavir (r=0.336, p=0.223) or Ishak (r=0.289, p=0.262) global fibrosis scores nor with liver collagen 1 expression (r=0.260, p=0.222). In contrast, portal fibrosis score (r=0.515, p=0.013), predominantly portal α-SMA expression (r=0.519, p=0.015) and amount CD34-positive microvessels in the centrizonal region (r=0.604, p=0.004) correlated positively with APRi. Patients (n=10) who underwent liver transplantation had significantly higher APRi at presentation (1.34 vs. 0.77, p=0.017) compared to those who survived with native liver (n=19).
  
  
  CONCLUSIONS
  APRi correlates with portal fibrosis, expression of α-SMA and the amount of CD34-positive microvessels, suggesting that APRi predicts native liver survival by reflecting portal myofibroblastic cell activation, fibrogenesis and associated neovascularization.
authors.affiliation: Department of Pediatric Surgery, Pediatric Liver and Gut Research Group, Children's Hospital, Helsinki University Central Hospital, 00290 Helsinki, Finland. Electronic address: jasasu@yahoo.com.
authors.forename: Janne S
authors.initials: JS
authors.lastname: Suominen
authors.affiliation: Department of Pediatric Surgery, Pediatric Liver and Gut Research Group, Children's Hospital, Helsinki University Central Hospital, 00290 Helsinki, Finland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Lampela
authors.affiliation: Department of Pathology, HUSLAB, Helsinki University Central Hospital, 00290 Helsinki, Finland.
authors.forename: Päivi
authors.initials: P
authors.lastname: Heikkilä
authors.affiliation: Department of Pathology, HUSLAB, Helsinki University Central Hospital, 00290 Helsinki, Finland.
authors.forename: Jouko
authors.initials: J
authors.lastname: Lohi
authors.affiliation: Department of Pediatrics, Children's Hospital, Helsinki University Central Hospital, 00290 Helsinki, Finland.
authors.forename: Hannu
authors.initials: H
authors.lastname: Jalanko
authors.affiliation: Department of Pediatric Surgery, Pediatric Liver and Gut Research Group, Children's Hospital, Helsinki University Central Hospital, 00290 Helsinki, Finland.
authors.forename: Mikko P
authors.initials: MP
authors.lastname: Pakarinen
mesh_terms: D001219:Aspartate Aminotransferases / Q000378:metabolism*; D001656:Biliary Atresia / Q000097:blood / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D015415:Biomarkers / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism*; D003661:Decision Support Techniques; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D008099:Liver / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009389:Neovascularization, Pathologic; D010976:Platelet Count; D011171:Portoenterostomy, Hepatic; D011379:Prognosis
chemical_list: D015415:Biomarkers; D001219:Aspartate Aminotransferases
keywords: Biliary atresia; CD34; Collagen 1; Liver fibrosis; Neovascularization; α-SMA