title: Liver collagen proportionate area predicts decompensation in patients with recurrent hepatitis C virus cirrhosis after liver transplantation.
abstract: OBJECTIVE
  Current histological scoring systems do not subclassify cirrhosis. Computer-assisted digital image analysis (DIA) of Sirius Red-stained sections measures fibrosis morphologically producing a fibrosis ratio (collagen proportionate area [CPA]). CPA could have prognostic value within a disease stage, such as cirrhosis. The aim of the present study was to evaluate CPA in patients with recurrent hepatitis C virus (HCV) allograft cirrhosis and assess its relationship with hepatic venous pressure gradient (HVPG).
  
  
  METHODS
  In 121 consecutively-transplanted HCV patients with HVPG, measured contemporaneously with transjugular liver biopsies, 65 had Ishak stage 5 or 6 disease (43 with HVPG measurement). Biopsies were stained with Sirius Red for DIA, and the collagen content was expressed as a CPA. In three cases, a tissue for Sirius Red staining was not obtained, and the patients were excluded.
  
  
  RESULTS
  Sixty-two patients were analyzed. The median HVPG was 8 mmHg (interquartile range [IQR]: 5-10). Portal hypertension (HVPG ≥ 6 < 10 mmHg) was present in 30 (69.8%), and HVPG ≥ 10 mmHg in 13 (30.2%). The median CPA was 16% (IQR 10.75-23.25). Median Child-Pugh score and HVPG were not significantly different between Ishak fibrosis stage 5 or 6, whereas CPA was statistically different: 13% in stage 5 (IQR 8.3-12.4) versus 23% in stage 6 (IQR 17-33.7, P < 0.001). In the multivariate analysis, CPA was the only variable significantly associated with clinically-significant portal hypertension (HVPG ≥ 10 mmHg, odds ratio: 1.085, confidence interval: 1.004-1.172, P = 0.040). A CPA of 14% was the best cut-off value for clinically-significant portal hypertension (CSPH) and liver decompensation, which occurred in 24 patients. Event-free survival was significantly shorter in patients with CSPH or with a CPA value ≥ 14%, or with a combination of both.
  
  
  CONCLUSIONS
  In Ishak stages 5 and 6, CPA correlated with HVPG, but had a wider range of values, suggesting a greater sensitivity for distinguishing "early" from "late" severe fibrosis/cirrhosis. CPA was a unique, independent predictor of HVPG ≥ 10 mmHg. CPA can be used to subclassify cirrhosis and for prognostic stratification.
authors.affiliation: The Royal Free Sheila Sherlock Liver Centre and University Department of Surgery, UCL and Royal Free Hospital, London, UK. vcalvaruso@libero.it
authors.forename: Vincenza
authors.initials: V
authors.lastname: Calvaruso
authors.forename: Amar Paul
authors.initials: AP
authors.lastname: Dhillon
authors.forename: Emanuel
authors.initials: E
authors.lastname: Tsochatzis
authors.forename: Pinelopi
authors.initials: P
authors.lastname: Manousou
authors.forename: Federica
authors.initials: F
authors.lastname: Grillo
authors.forename: Giacomo
authors.initials: G
authors.lastname: Germani
authors.forename: David
authors.initials: D
authors.lastname: Patch
authors.forename: James
authors.initials: J
authors.lastname: O'Beirne
authors.forename: Andrew Kenneth
authors.initials: AK
authors.lastname: Burroughs
mesh_terms: D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D003094:Collagen / Q000032:analysis*; D006503:Hepatic Veins / Q000503:physiopathology; D019698:Hepatitis C, Chronic / Q000150:complications*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008099:Liver / Q000737:chemistry* / Q000473:pathology; D008103:Liver Cirrhosis / Q000378:metabolism / Q000473:pathology / Q000601:surgery / Q000821:virology*; D016031:Liver Transplantation / Q000473:pathology*; D011379:Prognosis; D011446:Prospective Studies; D012008:Recurrence; D012720:Severity of Illness Index; D014690:Venous Pressure / Q000502:physiology
chemical_list: D015415:Biomarkers; D003094:Collagen