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).