title: Automated morphometry provides accurate and reproducible virtual staging of liver fibrosis in chronic hepatitis C.
abstract: BACKGROUND
  Liver fibrosis staging provides prognostic value, although hampered by observer variability. We used digital analysis to develop diagnostic morphometric scores for significant fibrosis, cirrhosis and fibrosis staging in chronic hepatitis C.
  
  
  METHODS
  We automated the measurement of 44 classical and new morphometric descriptors. The reference was histological METAVIR fibrosis (F) staging (F0 to F4) on liver biopsies. The derivation population included 416 patients and liver biopsies ≥20 mm-length. Two validation population included 438 patients.
  
  
  RESULTS
  In the derivation population, the area under the receiver operating characteristic (AUROC) for clinically significant fibrosis (F stage ≥2) of a logistic score combining 5 new descriptors (stellar fibrosis area, edge linearity, bridge thickness, bridge number, nodularity) was 0.957. The AUROC for cirrhosis of 6 new descriptors (edge linearity, nodularity, portal stellar fibrosis area, portal distance, granularity, fragmentation) was 0.994. Predicted METAVIR F staging combining 8 morphometric descriptors agreed well with METAVIR F staging by pathologists: κ = 0.868. Morphometric score of clinically significant fibrosis had a higher correlation with porto-septal fibrosis area (r s = 0.835) than METAVIR F staging (r s = 0.756, P < 0.001) and the same correlations with fibrosis biomarkers, e.g., serum hyaluronate: r s = 0.484 versus r s = 0.476 for METAVIR F (P = 0.862). In the validation population, the AUROCs of clinically significant fibrosis and cirrhosis scores were, respectively: 0.893 and 0.993 in 153 patients (biopsy < 20 mm); 0.955 and 0.994 in 285 patients (biopsy ≥ 20 mm). The three morphometric diagnoses agreed with consensus expert reference as well as or better than diagnoses by first-line pathologists in 285 patients, respectively: significant fibrosis: 0.733 versus 0.733 (κ), cirrhosis: 0.900 versus 0.827, METAVIR F: 0.881 versus 0.865.
  
  
  CONCLUSIONS
  The new automated morphometric scores provide reproducible and accurate diagnoses of fibrosis stages via "virtual expert pathologist."
authors.affiliation: HIFIH Laboratory, Unité Propre de Recherche de l'Enseignement Supérieur 3859, Sructure Fédérative de Recherche 4208, LUNAM University, Angers, France ; Department of Liver-Gastroenterology, LUNAM University, Angers, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Calès
authors.affiliation: HIFIH Laboratory, Unité Propre de Recherche de l'Enseignement Supérieur 3859, Sructure Fédérative de Recherche 4208, LUNAM University, Angers, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Chaigneau
authors.affiliation: HIFIH Laboratory, Unité Propre de Recherche de l'Enseignement Supérieur 3859, Sructure Fédérative de Recherche 4208, LUNAM University, Angers, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Hunault
authors.affiliation: HIFIH Laboratory, Unité Propre de Recherche de l'Enseignement Supérieur 3859, Sructure Fédérative de Recherche 4208, LUNAM University, Angers, France ; Department of Cellular and Tissue Pathology, CHU Angers, LUNAM University, Angers, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Michalak
authors.affiliation: Department of LARIS Laboratory, Unité Propre de Recherche de l'Enseignement Supérieur 7315, LUNAM University, Angers, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Cavaro-Menard
authors.affiliation: Department of LARIS Laboratory, Unité Propre de Recherche de l'Enseignement Supérieur 7315, LUNAM University, Angers, France.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Fasquel
authors.affiliation: HIFIH Laboratory, Unité Propre de Recherche de l'Enseignement Supérieur 3859, Sructure Fédérative de Recherche 4208, LUNAM University, Angers, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Bertrais
authors.affiliation: HIFIH Laboratory, Unité Propre de Recherche de l'Enseignement Supérieur 3859, Sructure Fédérative de Recherche 4208, LUNAM University, Angers, France ; Department of Cellular and Tissue Pathology, CHU Angers, LUNAM University, Angers, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Rousselet
keywords: Cirrhosis; METAVIR staging; digital histopathology; image analysis; liver biopsy