title: Quantification of portal-bridging fibrosis area more accurately reflects fibrosis stage and liver stiffness than whole fibrosis or perisinusoidal fibrosis areas in chronic hepatitis C.
abstract: Morphometry provides an objective evaluation of fibrosis in liver diseases. We developed an image analysis algorithm using automated thresholding and segmentation to separately quantify the areas and the fractal dimensions of portal-bridging fibrosis and perisinusoidal fibrosis in chronic hepatitis C liver biopsies. We studied 427 digitized liver biopsies and compared the automated measures of the different fibrosis compartments with (1) the Metavir F (fibrosis) and A (activity) histological scores, (2) the digitally assessed area of steatosis, and (3) the liver stiffness measured by elastography (Fibroscan). The perisinusoidal fibrosis area was higher than that of portal fibrosis in stages ≤F2; it reached its highest value in F2 stage and stabilized thereafter. The F3 stage was characterized by equal proportions of portal-bridging and perisinusoidal fibrosis, whereas portal-bridging area was predominant in cirrhosis. Measurement of portal-bridging fibrosis showed highly significantly different values between contiguous F stages; the ratio of portal-bridging fibrosis/perisinusoidal fibrosis displayed less overlap between Metavir stages than did the whole fibrosis area values. Fractal dimension showed that portal-bridging fibrosis tended to display a homogeneous surface-like spatial organization, whereas perisinusoidal fibrosis appeared more heterogeneous according to stage and curvilinear. The portal-bridging fibrosis area was low in cases with low Metavir activity and little steatosis, and became predominant with increasing activity and steatosis. Using stepwise multiple linear regression analysis, the liver stiffness was independently correlated to the portal-bridging fibrosis area (first step, P<0.001), the steatosis area (second step, P<0.001), and the Metavir A grade (third step, P=0.001), but not to the perisinusoidal fibrosis area. Automated quantification in a large cohort of chronic hepatitis C showed that perisinusoidal fibrosis progressively grew in early fibrosis stages but did not increase in septal or cirrhotic stages and that the portal-bridging fibrosis area appeared as a more accurate tool to assess fibrosis progression than the whole fibrosis area.
authors.affiliation: Cellular and Tissue Pathology Department, University Hospital, CHU, Angers, France.
authors.forename: Jérémy
authors.initials: J
authors.lastname: Sandrini
authors.affiliation: 1] HIFIH Laboratory, UPRES 3859, SFR 4208, LUNAM University, Angers, France [2] Liver-Gastroenterology Department, University Hospital, CHU, Angers, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Boursier
authors.affiliation: HIFIH Laboratory, UPRES 3859, SFR 4208, LUNAM University, Angers, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Chaigneau
authors.affiliation: Pathology Department, University Hospital, Grenoble, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Sturm
authors.affiliation: 1] Liver-Gastroenterology Department, University Hospital, Grenoble, France [2] INSERM/UJF U823, IAPC, IAB, Grenoble, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Zarski
authors.affiliation: Pathology Department, University Hospital, Bordeaux, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Le Bail
authors.affiliation: 1] Liver-Gastroenterology Department, Haut-Lévêque University Hospital, Pessac, France [2] INSERM U1053, Bordeaux Segalen University, Bordeaux, France.
authors.forename: Victor
authors.initials: V
authors.lastname: de Ledinghen
authors.affiliation: 1] HIFIH Laboratory, UPRES 3859, SFR 4208, LUNAM University, Angers, France [2] Liver-Gastroenterology Department, University Hospital, CHU, Angers, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Calès
authors.affiliation: 1] Cellular and Tissue Pathology Department, University Hospital, CHU, Angers, France [2] HIFIH Laboratory, UPRES 3859, SFR 4208, LUNAM University, Angers, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Rousselet
mesh_terms: D000328:Adult; D000465:Algorithms; D018450:Disease Progression; D054459:Elasticity Imaging Techniques; D005234:Fatty Liver / Q000473:pathology*; D005260:Female; D019698:Hepatitis C, Chronic / Q000473:pathology*; D006801:Humans; D008099:Liver / Q000473:pathology*; D008103:Liver Cirrhosis / Q000473:pathology*; D008297:Male; D008875:Middle Aged