title: Hepatic steatosis estimated microscopically versus digital image analysis.
abstract: OBJECTIVE
  Evaluate in liver biopsies: (i) interobserver agreement of estimates of fat proportionate area (eFPA) and steatosis grading, (ii) the relationship between steatosis grades and measured fat proportionate area (mFPA, digital image analysis), (iii) the accuracy of eFPA, (iv) to present images to aid standardization and accuracy of eFPA.
  
  
  METHODS
  Twenty-one liver biopsies were selected from the Royal Free Hospital (RFH) histopathology archive to represent the full range of histopathological steatosis severity. As many non-overlapping fields of parenchyma as possible were photographed at ×20 objective magnification from the biopsies (n = 651). A total of 15 sample images were selected to represent the range of steatosis seen. Twelve hepatopathologists from 11 sites worldwide independently evaluated the sample images for steatosis grade [normal (none)/mild/moderate/severe], and eFPA (% area of liver parenchyma occupied by fat).
  
  
  RESULTS
  The hepatopathologists had good linear correlation between eFPA and mFPA for sample images (r = 0.924, P < .001) and excellent concordance (kappa = 0.91, P < 0.001). Interobserver concordance of steatosis grade showed 'substantial agreement' (kappa = 0.64). There was significant difference between eFPA and mFPA in the sample images for mild, moderate and severe steatosis (P = 0.024, P < 0.001, P < 0.001 respectively): the observers consistently over-estimated the eFPA.
  
  
  CONCLUSIONS
  Hepatopathologists showed 'excellent' interobserver agreement in eFPA and 'substantial' agreement in assigning steatosis grade (precision was high). However, compared with mFPA, eFPA was inaccurate. eFPA systematically exceeds mFPA; generally the overestimation increases with severity of steatosis. Considering that non-invasive technologies for estimating liver fat utilize histopathology as reference, such assessments would benefit from quantitative validation of visually estimated microscopic liver fat percentages.
authors.affiliation: Department of Cellular Pathology, Royal Free London NHS Foundation Trust, London, UK. andrewhall1@nhs.net
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Hall
authors.forename: Amar P
authors.initials: AP
authors.lastname: Dhillon
authors.forename: Anna C
authors.initials: AC
authors.lastname: Green
authors.forename: Linda
authors.initials: L
authors.lastname: Ferrell
authors.forename: James M
authors.initials: JM
authors.lastname: Crawford
authors.forename: Venancio
authors.initials: V
authors.lastname: Alves
authors.forename: Charles
authors.initials: C
authors.lastname: Balabaud
authors.forename: Prithi
authors.initials: P
authors.lastname: Bhathal
authors.forename: Paulette
authors.initials: P
authors.lastname: Bioulac-Sage
authors.forename: Maria
authors.initials: M
authors.lastname: Guido
authors.forename: Prodromos
authors.initials: P
authors.lastname: Hytiroglou
authors.forename: Yasuni
authors.initials: Y
authors.lastname: Nakanuma
authors.forename: Valerie
authors.initials: V
authors.lastname: Paradis
authors.forename: Alberto
authors.initials: A
authors.lastname: Quaglia
authors.forename: Dale
authors.initials: D
authors.lastname: Snover
authors.forename: Neil
authors.initials: N
authors.lastname: Theise
authors.forename: Swan
authors.initials: S
authors.lastname: Thung
authors.forename: Wilson
authors.initials: W
authors.lastname: Tsui
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: van Leeuwen
mesh_terms: D050154:Adiposity; D001208:Asia; D001706:Biopsy; D001938:Brazil; D032921:Consensus; D005060:Europe; D005234:Fatty Liver / Q000473:pathology*; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008099:Liver / Q000473:pathology*; D008853:Microscopy; D015588:Observer Variation; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D014481:United States