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. 2020 Aug 28;10(9):643.
doi: 10.3390/diagnostics10090643.

An Improved qFibrosis Algorithm for Precise Screening and Enrollment into Non-Alcoholic Steatohepatitis (NASH) Clinical Trials

Wei-Qiang Leow  1   2 , Pierre Bedossa  3 , Feng Liu  4 , Lai Wei  5   6 , Kiat-Hon Lim  1   2 , Wei-Keat Wan  1 , Yayun Ren  7 , Jason Pik-Eu Chang  2   8 , Chee-Kiat Tan  2   8 , Aileen Wee  9   10 , George Boon-Bee Goh  2   8
Affiliations

An Improved qFibrosis Algorithm for Precise Screening and Enrollment into Non-Alcoholic Steatohepatitis (NASH) Clinical Trials

Wei-Qiang Leow et al. Diagnostics (Basel). .

Abstract

Background: Many clinical trials with potential drug treatment options for non-alcoholic fatty liver disease (NAFLD) are focused on patients with non-alcoholic steatohepatitis (NASH) stages 2 and 3 fibrosis. As the histological features differentiating stage 1 (F1) from stage 2 (F2) NASH fibrosis are subtle, some patients may be wrongly staged by the in-house pathologist and miss the opportunity for enrollment into clinical trials. We hypothesized that our refined artificial intelligence (AI)-based algorithm (qFibrosis) can identify these subtle differences and serve as an assistive tool for in-house pathologists.

Methods: Liver tissue from 160 adult patients with biopsy-proven NASH from Singapore General Hospital (SGH) and Peking University People's Hospital (PKUH) were used. A consensus read by two expert hepatopathologists was organized. The refined qFibrosis algorithm incorporated the creation of a periportal region that allowed for the increased detection of periportal fibrosis. Consequently, an additional 28 periportal parameters were added, and 28 pre-existing perisinusoidal parameters had altered definitions.

Results: Twenty-eight parameters (20 periportal and 8 perisinusoidal) were significantly different between the F1 and F2 cases that prompted a change of stage after a careful consensus read. The discriminatory ability of these parameters was further demonstrated in a comparison between the true F1 and true F2 cases as 26 out of the 28 parameters showed significant differences. These 26 parameters constitute a novel sub-algorithm that could accurately stratify F1 and F2 cases.

Conclusion: The refined qFibrosis algorithm incorporated 26 novel parameters that showed a good discriminatory ability for NASH fibrosis stage 1 and 2 cases, representing an invaluable assistive tool for in-house pathologists when screening patients for NASH clinical trials.

Keywords: NAFLD; NASH fibrosis; qFibrosis.

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Conflict of interest statement

Lai Wei consults for and received grants from AbbVie and Bristol-Myers Squibb. Lai Wei consults for Gilead. Y.R. declares current employment with HistoIndex Pte Ltd., Singapore. The rest of the authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(A,B) Creation of a new periportal region with altered perisinusoidal (PS) collagen parameters. (C) Second-harmonic generation (SHG)/two-photon excited fluorescence (TPEF) image of the periportal region (in green) and portal tract (in orange). (D) Hematoxylin and eosin (H&E)-stained image of the periportal region.
See this image and copyright information in PMC

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