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

doi:10.3390/diagnostics10090643

. 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 Bedossa³, Feng Liu⁴, Lai Wei^{5

6}, Kiat-Hon Lim^{1

2}, Wei-Keat Wan¹, Yayun Ren⁷, Jason Pik-Eu Chang^{2

8}, Chee-Kiat Tan^{2

8}, Aileen Wee^{9

10}, George Boon-Bee Goh^{2

8}

Affiliations

¹ Department of Anatomical Pathology, Singapore General Hospital, Singapore 169856, Singapore.
² Duke-NUS Medical School, National University of Singapore, Singapore 169857, Singapore.
³ Department of Pathology, Beaujon Hospital Paris Diderot University, 92110 Clichy, France.
⁴ Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing International Cooperation Base for Science and Technology on NAFLD Diagnosis, Beijing 100044, China.
⁵ Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing 100084, China.
⁶ Institute for Precision Medicine, Tsinghua University, Beijing 100084, China.
⁷ HistoIndex Pte. Ltd., Singapore 139955, Singapore.
⁸ Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore 169608, Singapore.
⁹ Department of Pathology, National University Hospital, Singapore 119074, Singapore.
¹⁰ Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.

PMID: 32872090
PMCID: PMC7554942
DOI: 10.3390/diagnostics10090643

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

Wei-Qiang Leow et al. Diagnostics (Basel). 2020.

. 2020 Aug 28;10(9):643.

doi: 10.3390/diagnostics10090643.

Authors

Affiliations

¹ Department of Anatomical Pathology, Singapore General Hospital, Singapore 169856, Singapore.
² Duke-NUS Medical School, National University of Singapore, Singapore 169857, Singapore.
³ Department of Pathology, Beaujon Hospital Paris Diderot University, 92110 Clichy, France.
⁴ Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing International Cooperation Base for Science and Technology on NAFLD Diagnosis, Beijing 100044, China.
⁵ Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing 100084, China.
⁶ Institute for Precision Medicine, Tsinghua University, Beijing 100084, China.
⁷ HistoIndex Pte. Ltd., Singapore 139955, Singapore.
⁸ Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore 169608, Singapore.
⁹ Department of Pathology, National University Hospital, Singapore 119074, Singapore.
¹⁰ Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.

PMID: 32872090
PMCID: PMC7554942
DOI: 10.3390/diagnostics10090643

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**
(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.

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References

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1. Satapathy S.K., Sanyal A.J. Epidemiology and Natural History of Nonalcoholic Fatty Liver Disease. Semin. Liver Dis. 2015;35:221–235. doi: 10.1055/s-0035-1562943. - DOI - PubMed
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1. Chalasani N., Younossi Z.M., LaVine J.E., Charlton M., Cusi K., Rinella M., Harrison S.A., Brunt E.M., Sanyal A.J. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2017;67:328–357. doi: 10.1002/hep.29367. - DOI - PubMed

Grants and funding

2016YFE0116800, 2018ZX09201002-001-005, 81870407/National Key R&D Program of China (2016YFE0116800) and grants from the China National Science and Technology Major Project for Infectious Diseases Control during the 13th Five-Year Plan Period (2018ZX09201002-001-005) and National Natural Science Foundati

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[1] EASL–EASD–EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J. Hepatol. 2016;64:1388–1402. doi: 10.1016/j.jhep.2015.11.004. - DOI - PubMed

[2] EASL–EASD–EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J. Hepatol. 2016;64:1388–1402. doi: 10.1016/j.jhep.2015.11.004. - DOI - PubMed

[3] Satapathy S.K., Sanyal A.J. Epidemiology and Natural History of Nonalcoholic Fatty Liver Disease. Semin. Liver Dis. 2015;35:221–235. doi: 10.1055/s-0035-1562943. - DOI - PubMed

[4] Satapathy S.K., Sanyal A.J. Epidemiology and Natural History of Nonalcoholic Fatty Liver Disease. Semin. Liver Dis. 2015;35:221–235. doi: 10.1055/s-0035-1562943. - DOI - PubMed

[5] Zhu J.-Z., Dai Y.-N., Wang Y.-M., Zhou Q.-Y., Yu C.-H., Li Y.-M. Prevalence of Nonalcoholic Fatty Liver Disease and Economy. Dig. Dis. Sci. 2015;60:3194–3202. doi: 10.1007/s10620-015-3728-3. - DOI - PubMed

[6] Zhu J.-Z., Dai Y.-N., Wang Y.-M., Zhou Q.-Y., Yu C.-H., Li Y.-M. Prevalence of Nonalcoholic Fatty Liver Disease and Economy. Dig. Dis. Sci. 2015;60:3194–3202. doi: 10.1007/s10620-015-3728-3. - DOI - PubMed

[7] Goh G.B.B., McCullough A.J. Natural History of Nonalcoholic Fatty Liver Disease. Dig. Dis. Sci. 2016;61:1226–1233. doi: 10.1007/s10620-016-4095-4. - DOI - PMC - PubMed

[8] Goh G.B.B., McCullough A.J. Natural History of Nonalcoholic Fatty Liver Disease. Dig. Dis. Sci. 2016;61:1226–1233. doi: 10.1007/s10620-016-4095-4. - DOI - PMC - PubMed

[9] Chalasani N., Younossi Z.M., LaVine J.E., Charlton M., Cusi K., Rinella M., Harrison S.A., Brunt E.M., Sanyal A.J. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2017;67:328–357. doi: 10.1002/hep.29367. - DOI - PubMed

[10] Chalasani N., Younossi Z.M., LaVine J.E., Charlton M., Cusi K., Rinella M., Harrison S.A., Brunt E.M., Sanyal A.J. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2017;67:328–357. doi: 10.1002/hep.29367. - DOI - PubMed

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

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