title: Image analysis of liver biopsy samples measures fibrosis and predicts clinical outcome.
abstract: OBJECTIVE
  Histopathological scoring of liver fibrosis mainly measures architectural abnormalities and requires a minimum biopsy size (⩾ 10 mm). Liver collagen quantification may allow use of small size biopsies and improve the prediction of clinical outcomes. This study evaluated the ability of the collagen proportional area (CPA) measurement to predict clinical outcomes.
  
  
  METHODS
  Clinical outcomes were determined using population based data-linkage for chronic hepatitis C (CHC) patients from 1992 to 2012. Quantitative digital image analysis of liver biopsies was used for CPA measurement.
  
  
  RESULTS
  533 patients with a biopsy size ⩾ 5 mm were included. Median follow up was 10.5 years. 26 developed hepatocellular carcinoma (HCC), 39 developed liver decompensation and 33 had liver related death. 453 had Metavir F0-F2 and 80 had F3-F4. CPA ranged from 1.3% to 44.6%. CPA and Metavir stage were independently associated with liver related death. Metavir stage, CPA stage and age were independently associated with HCC. CPA stage (C1: 0%-5%, C2: 5%-10%, C3: 10%-20%, C4: >20%) stratified risk and a significant difference in outcomes was present between all CPA stages for HCC and between C2-C3 and C3-C4 for decompensation and liver related death. The 15 year composite endpoint-free survival was 97% for C1, 89% for C2, 60% for C3, 7% for C4. C4 had significantly worse survival than ⩽ C3 (p<0.001) in cirrhotic patients.
  
  
  CONCLUSIONS
  CPA stage gave additional information regarding risk stratification for adverse clinical outcomes independent of Metavir stage.
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Perth, Australia; Department of Gastroenterology and Hepatology, Sir Charles Gairdner Hospital, Perth, Australia.
authors.forename: Yi
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Anatomical Pathology, PathWest, QEII Medical Centre, Perth, Australia.
authors.forename: W Bastiaan
authors.initials: WB
authors.lastname: de Boer
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Perth, Australia; Department of Gastroenterology and Hepatology, Sir Charles Gairdner Hospital, Perth, Australia.
authors.forename: Leon A
authors.initials: LA
authors.lastname: Adams
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Perth, Australia; Department of Gastroenterology and Hepatology, Sir Charles Gairdner Hospital, Perth, Australia.
authors.forename: Gerry
authors.initials: G
authors.lastname: MacQuillan
authors.affiliation: Institute of Health and Rehabilitation Research, University of Notre Dame, Perth, Australia.
authors.forename: Max K
authors.initials: MK
authors.lastname: Bulsara
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Perth, Australia; Department of Gastroenterology and Hepatology, Sir Charles Gairdner Hospital, Perth, Australia. Electronic address: gary.jeffrey@uwa.edu.au.
authors.forename: Gary P
authors.initials: GP
authors.lastname: Jeffrey
mesh_terms: D000328:Adult; D001706:Biopsy; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D003094:Collagen / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D019698:Hepatitis C, Chronic / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008103:Liver Cirrhosis / Q000378:metabolism / Q000473:pathology*; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis
chemical_list: D003094:Collagen
keywords: Chronic hepatitis C; Collagen proportional area; Histological stage; Liver complication; Liver related death