Tang, An
Dzyubak, Bogdan
Yin, Meng
Schlein, Alexandra
Henderson, Walter C.
Hooker, Jonathan C.
Delgado, Timoteo I.
Middleton, Michael S.
Zheng, Lin
Wolfson, Tanya
Gamst, Anthony
Loomba, Rohit
Ehman, Richard L.
Sirlin, Claude B. http://orcid.org/0000-0002-6639-9072
Funding for this research was provided by:
National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK075128, U01 DK061734)
National Center on Minority Health and Health Disparities (P60 MD00220)
National Center for Research Resources for the General Clinical Research Center at the University of California, San Diego grant (M01 RR000827)
National Institute of Biomedical Imaging and Bioengineering (NIBIB EB001981, NIBIB EB017197)
Fulbright Canada (N/A)
Institute of Nutrition, Metabolism and Diabetes (242199)
Fonds de Recherche du Québec - Santé (26993, 34939)
Article History
Received: 17 May 2021
Revised: 15 September 2021
Accepted: 4 October 2021
First Online: 20 December 2021
Declarations
:
: The scientific guarantor of this publication is Dr. Claude B. Sirlin.
: The authors of this manuscript declare relationships with the following companies:An Tang: Speaking honorarium from Eli Lilly. Equipment loan from Siemens Healthineers.Bogdan Dzyubak: The Mayo Clinic and Bogdan Dzyubak have intellectual property rights and a financial interest in magnetic resonance elastography technology. Bogdan Dzyubak is a part-time employee of Resoundant, Inc.Meng Yin: The Mayo Clinic and Meng Yin have intellectual property rights and a financial interest in magnetic resonance elastography technologyAlexandra Schlein: None to report.Walter C. Henderson: None to report.Jonathan C. Hooker: None to report.Timoteo I Delgado: None to report.Michael S. Middleton: Consultation to Arrowhead, Glympse, Kowa, Median, and Novo Nordisk; lab service agreements under auspices of UCSD from Alexion, AstraZeneca, Bristol-Myers Squibb, Celgene, Enanta, Galmed, Genzyme, Gilead, Guerbet, Intercept, Ionis, Janssen, Janssen, NuSirt, Organovo, Pfizer, Roche, Sanofi, Shire, Synageva, and Takeda; stockholder Pfizer; and co-founder Quantix Bio.Lin Zheng: None to report.Tanya Wolfson: None to report.Anthony Gamst: None to report.Rohit Loomba: Rohit Loomba serves as a consultant for Aardvark Therapeutics, Altimmune, Anylam/Regeneron, Amgen, Arrowhead Pharmaceuticals, AstraZeneca, Bristol-Myer Squibb, CohBar, Eli Lilly, Galmed, Gilead, Glympse bio, Hightide, Inipharm, Intercept, Inventiva, Ionis, Janssen Inc., Madrigal, Metacrine, Inc., NGM Biopharmaceuticals, Novartis, Novo Nordisk, Merck, Pfizer, Sagimet, Theratechnologies, 89 bio, and Viking Therapeutics. In addition, his institution 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 Sonic Incytes. He is also co-founder of Liponexus, Inc.Richard L. Ehman: The Mayo Clinic and Richard L Ehman have intellectual property rights and a financial interest in magnetic resonance elastography technologyClaude B. Sirlin: Dr. Sirlin reports grants from GE, Siemens, Philips, Bayer, Foundation of NIH, Gilead, and Pfizer (grant is to UW-Madison; 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, Takeda; royalties from Wolters Kluwer for educational material outside the submitted work; honoraria to the institution from Medscape for educational material outside the submitted work; ownership of stock options in Livivos; unpaid position in advisory board to Quantix Bio.
: Tanya Wolfson, Lin Zheng, and Anthony Gamst are biostatisticians. Tanya Wolfson and Lin Zheng performed statistical analysis of the data under the supervision of Anthony Gamst. Tanya Wolfson controlled the data. Tanya Wolfson, Lin Zheng, and Anthony Gamst are not employed by or are consultants for any company in the medical industry.
: This is a retrospective analysis of 2D MRE and liver biopsy data acquired prospectively in adults with known or suspected NAFLD at one clinical/imaging site and analyzed as part of this retrospective analysis at two analysis centers. Subjects in the parent studies provided written informed consent.
: Institutional Review Board approval was obtained at the University of California, San Diego, and was not required a Mayo Clinic, Rochester, for this retrospective study.
: The MRE and liver biopsy data for this retrospective analysis is compiled from three separate prior prospective, HIPAA-compliant, IRB-approved studies in adults with known or suspected NAFLD performed at UCSD between June 2011 and March 2015. Those studies were individually reported in 3 publications (references below and PDFs attached to the current submission).Park CC, Nguyen P, Hernandez C, Bettencourt R, Ramirez K, Fortney L, Hooker J, Sy E, Savides MT, Alquiraish MH, Valasek MA, Rizo E, Richards L, Brenner D, Sirlin CB, Loomba R. Magnetic resonance elastography vs transient elastography in detection of fibrosis and noninvasive measurement of steatosis in patients with biopsy-proven nonalcoholic fatty liver disease. <i>Gastroenterology</i>. 2017 Feb;152(3):598-607.e2. doi: 10.1053/j.gastro.2016.10.026. Epub 2016 Oct 27. PMID: 27911262; PMCID: PMC5285304.Loomba R, Sirlin CB, Ang B, Bettencourt R, Jain R, Salotti J, Soaft L, Hooker J, Kono Y, Bhatt A, Hernandez L, Nguyen P, Noureddin M, Haufe W, Hooker C, Yin M, Ehman R, Lin GY, Valasek MA, Brenner DA, Richards L; San Diego Integrated NAFLD Research Consortium (SINC). Ezetimibe for the treatment of nonalcoholic steatohepatitis: assessment by novel magnetic resonance imaging and magnetic resonance elastography in a randomized trial (MOZART trial). <i>Hepatology</i>. 2015 Apr;61(4):1239-50. doi: 10.1002/hep.27647. Epub 2015 Feb 27. PMID: 25482832; PMCID: PMC4407930.Doycheva I, Cui J, Nguyen P, Costa EA, Hooker J, Hofflich H, Bettencourt R, Brouha S, Sirlin CB, Loomba R. Non-invasive screening of diabetics in primary care for NAFLD and advanced fibrosis by MRI and MRE. <i>Aliment Pharmacol Ther.</i> 2016 Jan;43(1):83-95. doi: 10.1111/apt.13405. Epub 2015 Sep 15. PMID: 26369383; PMCID: PMC4673036.In this analysis, we address knowledge gaps in adults with NAFLD not investigated or reported in the parent studies: (1) 2D MRE stiffness measurement reproducibility between different centers and between manual and automated analysis methods; (2) comparison of diagnostic accuracy for distinguishing dichotomized fibrosis stages between different centers; and (3) comparison of diagnostic accuracy for distinguishing dichotomized fibrosis stages between manual analysis and automated analysis.
: • Retrospective• Cross-sectional study• Multicenter study