title: Objective ranking of fibrosis in standard histologic sections of human neonatal liver: applicability to alpha1-antitrypsin deficiency.
abstract: BACKGROUND
  The etiologic heterogeneity of fibrotic liver disease has resulted in the formulation of diverse, often disease-specific, classification systems for biopsy assessment, based on tissue morphology and staining. Their qualitative nature and observer dependency remain a concern, and no classification exists for several significant conditions--for example, alpha1-antitrypsin deficiency (alpha1-ATD). The authors propose a disease- and morphology-independent numeric ranking system to objectively quantify fibrosis in a standard histologic section, based on its content of protein amino acids. This PNC system is applied to two cases of alpha1-ATD liver fibrosis.
  
  
  METHODS
  High-performance liquid chromatography separation of the 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC)-labeled acid hydrolysate of an individual needle biopsy section, followed by the calculation of specific amino acid ratios to eliminate confounding variables.
  
  
  RESULTS
  As required by the PNC system, three numeric values were identified per tissue section, one increasing (P quotient), one decreasing (N quotient), one constant (C quotient) as fibrosis progresses, assessed by calibration against Knodell-staged samples. Generated for the alpha1-ATD sections, these three coordinates numerically referenced the degree of fibrosis in a manner that in each case was consistent with the histologic evaluation, the laboratory values, and the clinical course.
  
  
  CONCLUSIONS
  Numeric, objective referencing of the degree of fibrosis in routine liver biopsy sections, based on the PNC system, is technically possible.
authors.affiliation: Department of Pediatrics, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, New York 10021, USA.
authors.forename: E
authors.initials: E
authors.lastname: Moustafellos
authors.forename: M
authors.initials: M
authors.lastname: Illueca
authors.forename: H E
authors.initials: HE
authors.lastname: Remotti
authors.forename: P A
authors.initials: PA
authors.lastname: Auld
authors.forename: H M
authors.initials: HM
authors.lastname: Hanauske-Abel
mesh_terms: D001706:Biopsy; D005260:Female; D006801:Humans; D007223:Infant; D008099:Liver / Q000473:pathology*; D008103:Liver Cirrhosis / Q000145:classification* / Q000473:pathology; D008297:Male; D019896:alpha 1-Antitrypsin Deficiency / Q000473:pathology*