Background: Serial surveillance biopsies demonstrate post-transplant inflammation and fibrosis in long-surviving pediatric liver allografts. These changes can ultimately lead to cirrhosis and graft failure. However, the histologic grading of biopsies with respect to fibrosis is a subjective process and could lead to over- or under-reporting the degree of fibrosis. Inaccurate assessments may lead to delays in needed treatment interventions. Our group sought to compare standard fibrosis assessments of serial allograft biopsies with digital image analysis (DIA) of trichrome stains.

Methods: The records and stored biopsies of patients who received liver transplants at our institution between 2007 and 2010 were retrospectively identified. Patient demographics, pathology reports and histologic specimens through June 2015 were collected. Biopsies were analyzed for rejection according to the Rejection Activity Index (RAI) and for fibrosis using the METAVIR scoring system. Representative trichrome stains of each biopsy sample were subject to DIA. The slides were digitally scanned by Aperio's automated digital scanner at 40X magnification. Red/magenta staining of hepatocytes was designated as “positive”, and areas of fibrosis (blue) were designated as “negative”. The selected image was analyzed by Aperio's Positive Pixel Count Algorithm V 9.1 installed with ImageScope. The analysis output included number of the total “positive” & “negative” pixels and positive/negative rations for the total biopsy surface. Spearman's correlation and ANOVA were used to assess DIA fibrosis ratio in relation to METAVIR staging and RAI.

Results: Twenty patients and 131 biopsies were analyzed. The mean DIA fibrosis ratio differed significantly among all METAVIR stages with the exception of stage 0 to stage 1. No stage 4 biopsies were available from the patient samples. Mean DIA fibrosis ratios increased with each fibrosis stage (Stage 0: 0.029; Stage 1: 0.034; Stage 2: 0.060; Stage 3: 0.098). Spearman correlation was 0.43 (p value 0.001). DIA fibrosis ratios did not correlate significantly with RAI scores.

Conclusions: DIA of biopsy specimens was demonstrated to be a reliable assessment of fibrosis in pediatric liver allografts. Long-term assessments of serial biopsies digitally may be a unique tool to better identify subtle yet significant fibrosis progression.

CITATION INFORMATION: Fischer R, Foster S, Daniel J, Hendrickson R, Andrews W, Kats A. Digital Image Analysis of Pediatric Liver Allograft Biopsies Correlates with METAVIR Fibrosis Score. Am J Transplant. 2017;17 (suppl 3).

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