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  • Perspective
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Digital pathology for nonalcoholic steatohepatitis assessment

Nature Reviews Gastroenterology & Hepatology volume 21, pages 57–69 (2024)Cite this article

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Abstract

Histological assessment of nonalcoholic fatty liver disease (NAFLD) has anchored knowledge development about the phenotypes of the condition, their natural history and their clinical course. This fact has led to the use of histological assessment as a reference standard for the evaluation of efficacy of drug interventions for nonalcoholic steatohepatitis (NASH) — the more histologically active form of NAFLD. However, certain limitations of conventional histological assessment systems pose challenges in drug development. These limitations have spurred intense scientific and commercial development of machine learning and digital approaches towards the assessment of liver histology in patients with NAFLD. This research field remains an area in rapid evolution. In this Perspective article, we summarize the current conventional assessment of NASH and its limitations, the use of specific digital approaches for histological assessment, and their application to the study of NASH and its response to therapy. Although this is not a comprehensive review, the leading tools currently used to assess therapeutic efficacy in drug development are specifically discussed. The potential translation of these approaches to support routine clinical assessment of NAFLD and an agenda for future research are also discussed.

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Fig. 1: Typical histological changes of steatotic liver disease.
Fig. 2: Histological artefacts that might interfere with image analysis.
Fig. 3: Factors affecting the results of studies using digital approaches for pathology assessment of nonalcoholic steatohepatitis.
Fig. 4: Digital pathology platforms and the initial scanning of glass slide images.
Fig. 5: Fibrosis stages highlighted by second harmonic generation technology.
Fig. 6: Analysis of fibrosis regression.

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Acknowledgements

The authors thank the VCU Stravitz‐Sanyal Institute for Liver Disease and Metabolic Health, the RO1 DK129564 and the Intramural Research Program of the National Institutes of Health, National Cancer Institute.

Author information

Authors and Affiliations

  1. Stravitz‐Sanyal Institute for Liver Disease and Metabolic Health, Virginia Commonwealth University School of Medicine, Richmond, VA, USA

    Arun J. Sanyal

  2. Food and Drug Administration, Silver Spring, MD, USA

    Prakash Jha

  3. Post‐Mortem Section Laboratory of Pathology Center for Cancer Research National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    David E. Kleiner

Authors
  1. Arun J. Sanyal
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  2. Prakash Jha
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  3. David E. Kleiner
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Contributions

All authors researched data for the article. All authors contributed substantially to discussion of the content. A.J.S. wrote the article and reviewed and/or edited the manuscript before submission.

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Correspondence to Arun J. Sanyal.

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Competing interests

A.J.S. has served as a consultant to Path‐AI, HistoIndex, Fibronest, Biocellvia, Merck, Pfizer, Eli Lilly, Novo Nordisk, Boehringer Ingelheim, AstraZeneca, Akero, Intercept, Madrigal, Northsea, Takeda, Regeneron, Genentech, Alnylam, Roche, GlaxoSmithKline, Novartis, Tern, Fractyl, Inventiva, Gilead and Target Pharmasolutions, has stock options in Genfit, Tiziana, Durect, Inversago and Hemoshear, and receives royalties from Uptodate and Elsevier. His institution has received grants from Intercept, Pfizer, Merck, Bristol Myers Squibb, Eli Lilly, Novo Nordisk, Boehringer Ingelheim, AstraZeneca, Novartis and Madrigal. Virginia Commonwealth Univerisity has a collaborative agreement with Avant Sante. D.E.K. has uncompensated collaborative projects with HistoIndex and HighTide. P.J. declares no competing interests.

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Nature Reviews Gastroenterology & Hepatology thanks Michael Pavlides and Olivier Govaere for their contribution to the peer review of this work.

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Sanyal, A.J., Jha, P. & Kleiner, D.E. Digital pathology for nonalcoholic steatohepatitis assessment. Nat Rev Gastroenterol Hepatol 21, 57–69 (2024). https://doi.org/10.1038/s41575-023-00843-7

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