Development and validation of an automated optical imaging system to differentiate severity of hepatitis B- and non-alcoholic steatohepatitis-related fibrosis in patients with concomitant disease
AASLD LiverLearning®. Chang J. Nov 11, 2016; 143305
Topic: Clinical and Translational Fibrosis Research
Dr. Jason Chang
Dr. Jason Chang
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TITLE: Development and validation of an automated optical imaging system to differentiate severity of hepatitis B- and non-alcoholic steatohepatitis-related fibrosis in patients with concomitant disease

This work received funding support from HistoIndex Pte Ltd, Singapore and Diagnostics Development Hub, Exploit Technologies Pte Ltd, Singapore

Current histological grading systems for hepatic fibrosis are based on disease-specific patterns of fibrosis distribution. Co-existence of chronic hepatitis B (CHB) and non-alcoholic steatohepatitis (NASH) is common. It is difficult to differentiate severity of fibrosis contributed by the individual diseases, which is important in guiding therapeutic decisions in the era of anti-fibrotic therapy. Second harmonic generation (SHG) microscopy is a novel optical tissue-imaging system that provides detailed 3D-characterisation of collagen fibres. We aim to develop and validate SHG microscopy for automated staging of fibrosis in CHB, NASH and in concomitant CHB-NASH.

SHG microscopy using GenesisTM(HistoIndex®, Singapore) was performed on liver biopsy specimens from patients with pure CHB (n=23) and pure NASH (n=43). Algorithms were developed to identify specific SHG collagen characteristics that predict fibrosis in CHB, and separately in NASH. Accuracy of SHG for staging of fibrosis in CHB (using METAVIR) and NASH (using Brunt fibrosis staging) was assessed by AUROC analysis. The algorithms were subsequently validated in 27 patients with concomitant CHB-NASH.

A fibrosis index (M-index) comprising 6 unique collagen parameters defined by SHG microscopy was developed in the CHB group. Similarly, a B-index comprising a separate set of SHG-defined collagen parameters was developed in the NASH group. Unique collagen features associated with CHB fibrosis included collagen string length and width which were predominant in the portal areas. In contrast, collagen features in NASH fibrosis included short collagen strings in the central and perisinusoidal regions. M-index correlated well with METAVIR stage (r=0.863, p<0.001), with AUROCs of 0.895, 0.962, 0.962 and 0.955 for prediction of F1, F2, F3 and F4, respectively. Similarly, B-index had excellent correlation with Brunt fibrosis stage (r=0.935, p<0.001) with AUROCs of 0.915, 0.991, 0.987 and 0.992 for B1, B2, B3 and B4, respectively. The ability to stage CHB and NASH-related fibrosis individually using the respective indexes was then validated in the group with concomitant CHB-NASH. AUROC of M-index and B-index for METAVIR and Brunt fibrosis stages in CHB-NASH ranged from 0.806-0.917 and 0.920-1.000 respectively. Sensitivity/specificity of M-index>1.5 for METAVIR F3/F4 was 84.6%/85.7%.while that of B-index>1.2 for Brunt stage 3/4 fibrosis was 85.7%/92.3% .

SHG optical microscopy is an automated system that is able to assess and classify the severity of individual components of CHB and NASH-related fibrosis in patients with concomitant CHB-NASH.
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