Diagnostic accuracy of magnetic resonance imaging hepatic proton density fat fraction in pediatric nonalcoholic fatty liver disease

• Type of Material: Article
• Authors: Michael S. Middleton, University of California San Diego; Mark L. Van Natta, Johns Hopkins Bloomberg School of Public Health; Elhamy R. Heba, University of California San Diego; Adina Alazraki, Emory University; Andrew T. Trout, Cincinnati Childrens Hospital Medical Center; Prakash Masand, Texas Children's Hospital; Elizabeth M. Brunt, Washington University; David E. Kleiner, National Cancer Institute; Edward Doo, National Institute of Diabetes and Digestive and Kidney Diseases; James Tonascia, Johns Hopkins Bloomberg School of Public Health; Joel E. Lavine, Columbia University; Wei Shen, Columbia University; Gavin Hamilton, University of California San Diego; Jeffrey B. Schwimmer, University of California San Diego; Claude B. Sirlin, University of California San Diego
• Language: English
• Date: 2018-03-01
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017 by the American Association for the Study of Liver Diseases. This article has been contributed to by US Government employees and their work is in the public domain in the USA.
• Final Published Version (URL): http://dx.doi.org/10.1002/hep.29596
• Title of Journal or Parent Work: Hepatology
• ISSN: 0270-9139
• Volume: 67
• Issue: 3
• Start Page: 858
• End Page: 872
• Grant/Funding Information: This study was supported in part by the Intramural Research Program of the NIH, National Cancer Institute.; We would like to acknowledge support from the following sources: NIDDK U01 DK061713; NIDDK U01 DK061718; NIDDK U01 DK061728; NIDDK U01 DK061730; NIDDK U01 DK061731; NIDDK U01 DK061732; NIDDK U01 DK061734; NIDDK U01 DK061737; NIDDK U01 DK061738; NCATS UL1 TR000004; NCATS UL1 TR000006; NCATS UL1 TR000040; NCATS UL1 TR000077; NCATS UL1 TR000100; NCATS UL1 TR000150; NCATS UL1 TR000423; NCATS UL1 TR000424; NCATS UL1 TR000448; NCATS UL1 TR000454
• Keywords: Life Sciences & Biomedicine; STEATOSIS GRADES; OBESE SUBJECTS; STEATOHEPATITIS; QUANTIFICATION; MAGNITUDE-BASED MRI; CHILDREN; Gastroenterology & Hepatology; CARDIOVASCULAR RISK-FACTORS; METABOLIC SYNDROME; Science & Technology; FLIP-ANGLE; TRANSIENT ELASTOGRAPHY
• Research Categories: Health Sciences, Pathology; Health Sciences, Nutrition

Abstract

We assessed the performance of magnetic resonance imaging (MRI) proton density fat fraction (PDFF) in children to stratify hepatic steatosis grade before and after treatment in the Cysteamine Bitartrate Delayed-Release for the Treatment of Nonalcoholic Fatty Liver Disease in Children (CyNCh) trial, using centrally scored histology as reference. Participants had multiecho 1.5 Tesla (T) or 3T MRI on scanners from three manufacturers. Of 169 enrolled children, 110 (65%) and 83 (49%) had MRI and liver biopsy at baseline and at end of treatment (EOT; 52 weeks), respectively. At baseline, 17% (19 of 110), 28% (31 of 110), and 55% (60 of 110) of liver biopsies showed grades 1, 2, and 3 histological steatosis; corresponding PDFF (mean ± SD) values were 10.9 ± 4.1%, 18.4 ± 6.2%, and 25.7 ± 9.7%, respectively. PDFF classified grade 1 versus 2-3 and 1-2 versus 3 steatosis with areas under receiving operator characteristic curves (AUROCs) of 0.87 (95% confidence interval [CI], 0.80, 0.94) and 0.79 (0.70, 0.87), respectively. PDFF cutoffs at 90% specificity were 17.5% for grades 2-3 steatosis and 23.3% for grade 3 steatosis. At EOT, 47% (39 of 83), 41% (34 of 83), and 12% (10 of 83) of biopsies showed improved, unchanged, and worsened steatosis grade, respectively, with corresponding PDFF (mean ± SD) changes of –7.8 ± 6.3%, –1.2 ± 7.8%, and 4.9 ± 5.0%, respectively. PDFF change classified steatosis grade improvement and worsening with AUROCs (95% CIs) of 0.76 (0.66, 0.87) and 0.83 (0.73, 0.92), respectively. PDFF change cut-off values at 90% specificity were –11.0% and +5.5% for improvement and worsening. Conclusion: MRI-estimated PDFF has high diagnostic accuracy to both classify and predict histological steatosis grade and change in histological steatosis grade in children with NAFLD. (Hepatology 2018;67:858–872).