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Non-Invasive Biomarkers of Nonalcoholic Steatohepatitis: the FNIH NIMBLE project

Nature Medicine volume 28, pages 430–432 (2022)Cite this article

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To the Editor — Nonalcoholic fatty liver disease (NAFLD) affects approximately one-quarter of the global adult population1. A subset of affected individuals worldwide have nonalcoholic steatohepatitis (NASH), a more progressive form of the disease that has a higher risk of advancing to cirrhosis and end-stage liver disease (ESLD). Given the enormous number of afflicted patients, identification of the subset at risk of disease progression is critically important for efficient therapy allocation.

NASH patients with fibrosis stage 2 or higher have elevated all-cause and liver-related mortality2, and those with high disease activity scores are at greater risk of fibrosis progression3. These at-risk NASH patients are the target population for therapeutic intervention beyond lifestyle improvement. Histopathological assessment is the current reference standard for diagnosis, risk stratification and therapeutic efficacy evaluation for NAFLD. Unfortunately, liver biopsy for histological assessment carries risks, including even rare mortality. Histopathological assessment is also susceptible to sampling error and intra- and inter-reader variability. These drawbacks of liver biopsy have limited biopsy-based assessment in routine practice and pose challenges in clinical trial design and interpretation. There is therefore a need for reliable non-invasive tools for the diagnosis, risk stratification and monitoring of the course of NAFLD.

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Fig. 1: The FNIH NIMBLE project plan.

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Acknowledgements

We acknowledge support from the Global Liver Institute, USA, and the US FDA. The NIMBLE project is sponsored by the FNIH and is a public–private partnership supported by multiple entities including AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Echosens, GE Healthcare, Genentech, Gilead Sciences, Intercept Pharmaceuticals, Novo Nordisk, Pfizer and Takeda Development Center Americas. Key collaborators who provide in-kind support to NIMBLE include AMRA Medical, Canon Medical Systems USA, Echosens, GENFIT, GE Healthcare, Nordic Bioscience, OWL Metabolomics, Philips Ultrasound, P-Value, Hologic SuperSonic Imagine, Siemens Healthineers and Siemens Medical Solutions USA.

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Authors and Affiliations

  1. Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, VA, USA

    Arun J. Sanyal

  2. AstraZeneca, Gaithersburg, MD, USA

    Sudha S. Shankar

  3. Regeneron Pharmaceuticals, Tarrytown, NY, USA

    Roberto A. Calle

  4. Center for Ultrasound Research & Translation, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Anthony E. Samir

  5. Liver Imaging Group, Department of Radiology, , University of California, San Diego, San Diego, CA, USA

    Claude B. Sirlin & Kathryn J. Fowler

  6. Pfizer, Cambridge, MA, USA

    Sarah P. Sherlock

  7. NAFLD Research Center, Division of Gastroenterology, Department of Medicine, University of California at San Diego, La Jolla, CA, USA

    Rohit Loomba

  8. P-Value, Jamestown, NC, USA

    Clayton A. Dehn

  9. Foundation for the National Institutes of Health, North Bethesda, MD, USA

    Helen Heymann & Tania N. Kamphaus

Authors
  1. Arun J. Sanyal
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  2. Sudha S. Shankar
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  3. Roberto A. Calle
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  8. Kathryn J. Fowler
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  11. Tania N. Kamphaus
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Contributions

The manuscript was drafted by A.J.S. and was substantially revised and critiqued by all of the authors and approved by the authors prior to submission. The authors take full responsibility for the contents of this manuscript.

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Correspondence to Arun J. Sanyal.

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Competing interests

A.J.S. is President of Sanyal Biotechnology, has stock options in Genfit, Akarna, Tiziana, Indalo, Exhalenz and Durect; receives royalties from Elsevier and UptoDate; and has served as a consultant to Astra Zeneca, Janssen, Gilead, Terns, Histoindex, Path-AI, Inventiva, Amgen, Regeneron, Genentech, Merck, Valeant, Boehringer-Ingelheim, Bristol Myers Squibb, Fractyl, Lilly, Hemoshear, Novartis, Novo Nordisk, Pfizer, Intercept and Genfit. Virginia Commonwealth University has received grant support from Gilead, Salix, Tobira, Eli Lilly, Novo Nordisk, Celgene, Viking, Madrigal, Galmed, Pfizer, Bristol Myers, Intercept, Merck, Astra Zeneca, Mallinckrodt and Novartis. S.S.S. is an employee of Astra Zeneca. R.A.C. is employed by Regeneron Pharmaceuticals and is owner of restricted stock units from Regeneron and Pfizer. A.E.S. has served as a compensated consultant for Astra Zeneca, Bracco Diagnostics, Bristol Myers Squibb, General Electric, Gerson Lehman Group, Guidepoint Global Advisors, Supersonic Imagine, Novartis, Pfizer, Philips, Parexel Informatics and WorldCare Clinical; holds stock options in Remedy Medical, Rhino Healthtech and Ochre Bio; is a co-founder of, and holds equity in, Avira, Autonomus, Evidence Based Psychology, Klea, Katharos Laboratories, Quantix Bio and Sonoluminous; receives royalties from Elsevier and Katharos Laboratories; holds advisory board or committee memberships for General Electric, the FNIH and the Sano Center for Computational Personalized Medicine; and is a member of the Board of Governors of the American Institute for Ultrasound in Medicine. Massachusetts General Hospital has received research grant support and/or equipment for projects that A.E.S. has led from the Analogic Corporation, Canon, Echosens, General Electric, Hitachi, Philips, Siemens, Supersonic Imagine/Hologic, Toshiba Medical Systems, the US Department of Defense, Fujifilm Healthcare, the Foundation for the National Institutes of Health, Partners Healthcare, Toshiba Medical Systems and Siemens Medical Systems. C.B.S. reports grants from General Electric, Siemens, Philips, Bayer, the FNIH, Gilead and Pfizer (grant is to University of Wisconsin–Madison (UW-Madison); the University of California, San Diego (UCSD), is a subcontract to UW-Madison); personal consultation fees from Blade, Boehringer and Epigenomics; consultation under the auspices of the University to AMRA, BMS, Exact Sciences, GE Digital, IBM-Watson, and Pfizer; lab service agreements from Enanta, Gilead, ICON, Intercept, Nusirt, Shire, Synageva and Takeda; royalties from Wolters Kluwer for educational material outside the submitted work; honoraria to his institution, UCSD, from Medscape for educational material outside the submitted work; ownership of stock options in Livivos; and an unpaid position on an advisory board to Quantix Bio. S.P.S. is employed by Pfizer and is owner of restricted stock units from Pfizer. R.L. is co-founder of Liponexus, and serves as a consultant for Alnylam/Regeneron, Amgen, Arrowhead Pharmaceuticals, Astra Zeneca, Bristol-Myer Squibb, CohBar, Eli Lilly, Galmed, Gilead, Glympse bio, Inipharm, Intercept, Ionis, Janssen, Madrigal, Metacrine, NGM Biopharmaceuticals, Novartis, Novo Nordisk, Pfizer, Sagimet, 89 bio and Viking Therapeutics. UCSD has received grant support from Allergan, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, Galectin Therapeutics, Galmed Pharmaceuticals, Genfit, Gilead, Intercept, Inventiva, Janssen, Madrigal Pharmaceuticals, Merck, NGM Biopharmaceuticals, Pfizer and Siemens. K.J.F. reports grant support from General Electric, Bayer, Pfizer and Median; institutional consulting with General Electric; personal consulting with Bayer; an unpaid position on the advisory board of Quantix Bio; and lab service agreements from Enanta, Gilead, ICON, Intercept, Nusirt, Shire, Synageva and Takeda.

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Sanyal, A.J., Shankar, S.S., Calle, R.A. et al. Non-Invasive Biomarkers of Nonalcoholic Steatohepatitis: the FNIH NIMBLE project. Nat Med 28, 430–432 (2022). https://doi.org/10.1038/s41591-021-01652-8

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