Hepatic steatosis estimated microscopically versus digital image analysis

Andrew R. Hall, Amar P. Dhillon, Anna C. Green, Linda Ferrell, James M. Crawford, Venancio Alves, Charles Balabaud, Prithi Bhathal, Paulette Bioulac-Sage, Maria Guido, Prodromos Hytiroglou, Yasuni Nakanuma, Valerie Paradis, Alberto Quaglia, Dale Snover, Neil Theise, Swan Thung, Wilson Tsui, Dirk J. Van Leeuwen

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42 Scopus citations


Background & Aims: 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)926-935
Number of pages10
JournalLiver International
Issue number6
StatePublished - Jul 2013


  • Alcoholic liver disease
  • Digital image analysis
  • Estimated fat proportionate area
  • Fat proportionate area
  • Fat quantification
  • Measured fat proportionate area
  • Non-alcoholic fatty liver disease
  • Steatosis


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