title: Computer-assisted image analysis of liver collagen: relationship to Ishak scoring and hepatic venous pressure gradient.
abstract: Histopathological scoring of disease stage uses descriptive categories without measuring the amount of fibrosis. Collagen, the major component of fibrous tissue, can be quantified by computer-assisted digital image analysis (DIA) using histological sections. We determined relationships between DIA, Ishak stage, and hepatic venous pressure gradient (HVPG) reflecting severity of fibrosis. One hundred fifteen patients with hepatitis C virus (HCV) who had undergone transplantation had 250 consecutive transjugular liver biopsies combined with HVPG (median length, 22 mm; median total portal tracts, 12), evaluated using the Ishak system and stained with Sirus red for DIA. Liver collagen was expressed as collagen proportionate area (CPA). Median CPA was 6% (0.2-45), correlating with Ishak stage (stage 6 range, 13%-45%), and with HVPG (r = 0.62; P < 0.001). Median CPA was 4.1% when HVPG was less than 6 mm Hg and 13.8% when HVPG was 6 mm Hg or more (P < 0.0001) and 6% when HVPG was less than 10 mm Hg and 17.3% when HVPG was 10 mm Hg or higher (P < 0.0001). Only CPA, not Ishak stage/grade, was independently associated by logistic regression, with HVPG of 6 mm Hg or more [odds ratio, 1.206; 95% confidence interval (CI), 1.094-1.331; P < 0.001], or HVPG of 10 mm Hg or more (odds ratio, 1.105; 95% CI, 1.026-1.191; P = 0.009). CPA increased by 50% (3.6%) compared with 20% in HVPG (1 mm Hg) in 38 patients with repeated biopsies.
  
  
  CONCLUSIONS
  CPA assessed by DIA correlated with Ishak stage scores and HVPG measured contemporaneously. CPA was a better histological correlate with HVPG than Ishak stage, had a greater numerical change when HVPG was low, and resulted in further quantitation of fibrosis in cirrhosis.
authors.affiliation: The Royal Free Sheila Sherlock Liver Centre and Department of Surgery, Royal Free Hospital, London, UK.
authors.forename: Vincenza
authors.initials: V
authors.lastname: Calvaruso
authors.forename: Andrew Kenneth
authors.initials: AK
authors.lastname: Burroughs
authors.forename: Richard
authors.initials: R
authors.lastname: Standish
authors.forename: Pinelopi
authors.initials: P
authors.lastname: Manousou
authors.forename: Federica
authors.initials: F
authors.lastname: Grillo
authors.forename: Gioacchino
authors.initials: G
authors.lastname: Leandro
authors.forename: Sergio
authors.initials: S
authors.lastname: Maimone
authors.forename: Maria
authors.initials: M
authors.lastname: Pleguezuelo
authors.forename: Ilias
authors.initials: I
authors.lastname: Xirouchakis
authors.forename: Gian Piero
authors.initials: GP
authors.lastname: Guerrini
authors.forename: David
authors.initials: D
authors.lastname: Patch
authors.forename: Dominic
authors.initials: D
authors.lastname: Yu
authors.forename: James
authors.initials: J
authors.lastname: O'Beirne
authors.forename: Amar Paul
authors.initials: AP
authors.lastname: Dhillon
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D003094:Collagen / Q000032:analysis*; D005260:Female; D006503:Hepatic Veins / Q000503:physiopathology*; D006526:Hepatitis C / Q000150:complications; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008099:Liver / Q000473:pathology*; D008103:Liver Cirrhosis / Q000175:diagnosis* / Q000503:physiopathology / Q000821:virology; D016031:Liver Transplantation; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D014690:Venous Pressure
chemical_list: D003094:Collagen