title: Digital image analysis of collagen assessment of progression of fibrosis in recurrent HCV after liver transplantation.
abstract: OBJECTIVE
  Histological assessment of fibrosis progression is currently performed by staging systems which are not continuous quantitative measurements. We aimed at assessing a quantitative measurement of fibrosis collagen proportionate area (CPA), to evaluate fibrosis progression and compare it to Ishak stage progression.
  
  
  METHODS
  We studied a consecutive cohort of 155 patients with recurrent HCV hepatitis after liver transplantation (LT), who had liver biopsies at one year and were subsequently evaluated for progression of fibrosis using CPA and Ishak staging, and correlated with clinical decompensation. The upper quartile of distribution of fibrosis rates (difference in CPA or Ishak stage between paired biopsies) defined fast fibrosers.
  
  
  RESULTS
  Patients had 610 biopsies and a median follow-up of 116 (18-252) months. Decompensation occurred in 29 (18%) patients. Median Ishak stage progression rate was 0.42 units/year: (24 (15%) fast fibrosers). Median CPA fibrosis progression rate was 0.71%/year (36 (23%) fast fibrosers). Clinical decompensation was independently associated by Cox regression only with CPA (p=0.007), with AUROCs of 0.81 (95% CI 0.71-0.91) compared to 0.68 (95% CI 0.56-0.81) for Ishak stage. Fast fibrosis defined by CPA progression was independently associated with histological de novo hepatitis (OR: 3.77), older donor age (OR: 1.03) and non-use/discontinuation of azathioprine before 1 year post-LT (OR: 3.85), whereas when defined by Ishak progression, fast fibrosers was only associated with histological de novo hepatitis.
  
  
  CONCLUSIONS
  CPA fibrosis progression rate is a better predictor of clinical outcome than progression by Ishak stage. Histological de novo hepatitis, older donor age and non-use/discontinuation of azathioprine are associated with rapid fibrosis progression in recurrent HCV chronic hepatitis after liver transplantation.
authors.affiliation: The Royal Free Sheila Sherlock Liver Centre and Division of Surgery & Interventional Sciences, University College London, UK.
authors.forename: Pinelopi
authors.initials: P
authors.lastname: Manousou
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Burroughs
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Tsochatzis
authors.forename: Emmanuel T
authors.initials: ET
authors.lastname: Sochatzis
authors.forename: Grazia
authors.initials: G
authors.lastname: Isgro
authors.forename: Andrew
authors.initials: A
authors.lastname: Hall
authors.forename: Anna
authors.initials: A
authors.lastname: Green
authors.forename: Vincenza
authors.initials: V
authors.lastname: Calvaruso
authors.forename: Guang Li
authors.initials: GL
authors.lastname: Ma
authors.forename: Jeremy
authors.initials: J
authors.lastname: Gale
authors.forename: Gary
authors.initials: G
authors.lastname: Burgess
authors.forename: James
authors.initials: J
authors.lastname: O'Beirne
authors.forename: David
authors.initials: D
authors.lastname: Patch
authors.forename: Douglas
authors.initials: D
authors.lastname: Thorburn
authors.forename: Gioacchino
authors.initials: G
authors.lastname: Leandro
authors.forename: Amar Paul
authors.initials: AP
authors.lastname: Dhillon
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001379:Azathioprine / Q000627:therapeutic use; D001706:Biopsy; D015331:Cohort Studies; D003094:Collagen / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006526:Hepatitis C / Q000150:complications* / Q000453:epidemiology / Q000601:surgery*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008103:Liver Cirrhosis / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012044:Regression Analysis; D012307:Risk Factors; D012720:Severity of Illness Index; D028761:Withholding Treatment; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D003094:Collagen; D001379:Azathioprine