Article

Hepatic steatosis estimated microscopically versus digital image analysis

Department of Cellular Pathology, Royal Free London NHS Foundation Trust, London, UK.
Liver international: official journal of the International Association for the Study of the Liver (Impact Factor: 4.41). 03/2013; 33(6). DOI: 10.1111/liv.12162
Source: PubMed

ABSTRACT 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.
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).
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.
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.

Download full-text

Full-text

Available from: Andrew R Hall, Oct 21, 2014
2 Followers
 · 
136 Views
 · 
59 Downloads
  • [Show abstract] [Hide abstract]
    ABSTRACT: Computer-assisted automatic quantification (CAQ) was developed as an alternative method for diagnosis of hepatic steatosis in order to compensate for observer-dependent bias Here we aim to demonstrate that CAQ can provide an accurate and precise result in analysis of fatty content, but that it is inappropriate to validate CAQ by comparison with a conventional pathologist estimation (PE). Male rats were fed with a methionine-choline-deficient plus high-fat (MCD+HF) diet for 3days, 1week or 2weeks to induce mild, moderate or severe steatosis. Samples were collected from all liver lobes. Severity of hepatic steatosis was assessed by an experienced pathologist who estimated the percentage of hepatocytes containing lipid droplets. Fatty content was quantified by PE, CAQ, and biochemical analysis (BA). CAQ, PE and BA can correctly reflect severe fatty change. However, in the case of mild and moderate steatosis, PE could not reflect the true fatty content (r between PE and BA was <0). The result of CAQ correlated well with that of BA amongst the various degrees of severity of hepatic steatosis. In conclusion, due to a difference between event-based and surface-based analysis, it is inappropriate to validate the CAQ of hepatic steatosis by comparison with PE.
    11/2013; 18(4). DOI:10.1109/JBHI.2013.2282999
  • [Show abstract] [Hide abstract]
    ABSTRACT: Obesity and insulin resistance produce alterations in the liver's normal role in lipid metabolism resulting in a sequence of changes recognizable on liver biopsy. Hepatocellular fat vacuoles increase with BMI, producing steatosis. Steatohepatitis occurs when there is also cytoskeletal damage with loss of keratin filaments, ballooning of affected liver cells and formation of Mallory-Denk bodies. Activation of hepatic stellate cells produces fibrosis in the perisinusoidal spaces. With continuing fibrogenesis there is progression to bridging fibrosis and cirrhosis. Hepatocellular carcinoma may develop in the cirrhotic liver, but both hepatocellular adenoma and hepatocellular carcinoma may occur in pre-cirrhotic fatty liver disease.
    Clinics in liver disease 02/2014; 18(1):33-40. DOI:10.1016/j.cld.2013.09.010 · 2.70 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background & AimsGuideline images of specific fat proportionate area (FPA) percentages have recently been published to aid the histological assessment of liver steatosis as subjective estimates of FPA are usually overestimated. To assess, (i) the effect of guideline images on accuracy and concordance of estimated FPA (eFPA), (ii) experience of steatosis grading systems on eFPA, (iii) the effect of magnification on assessment of FPA (iv) and produce a range of guideline images at x4 objective magnification (OM). Methods Two circulations of sample images (C1 and C2) were circulated to UK liver external quality assessment histopathology scheme members who were asked to independently evaluate steatosis. Each circulation consisted of 15 images taken at both x20 and x4OM representing the full range of steatosis. C1 was distributed first, then C2 with guideline images of FPA 6weeks later. ResultsParticipants overestimated FPA in C1. In C2, there was significant improvement in accuracy (P<0.001) of eFPA for sample images with mFPA >5%. Concordance of x4OM eFPA was substantial in both circulations (C1K=0.878, C2K=0.724). Conclusion The tendency to overestimate eFPA has been corroborated and can be largely corrected with the use of guideline images (without needing digital image analysis). There is a need to redefine steatosis grades that are clinically significant and validated using an accurate quantification of steatosis.
    Liver international: official journal of the International Association for the Study of the Liver 06/2014; 34(9). DOI:10.1111/liv.12614 · 4.41 Impact Factor
Show more