No abstract

Magnetic Resonance Elastography (MRE) is promising for non-invasive assessment of fibrosis, a major determinant of outcome in nonalcoholic fatty liver disease (NAFLD). However, data in children are limited. Study aims were to determine accuracy of MRE for detection of fibrosis and advanced fibrosis in children with NAFLD, and to assess agreement between manual and novel automated reading methods. We performed a prospective, multi-center study of 2D-MRE in children with NAFLD. MR-elastograms were analyzed manually at 2 reading centers and using a new automated technique. Analysis using each approach was done independently. Correlations were determined between MRE analysis methods and fibrosis stage. Thresholds for classifying the presence of fibrosis and of advanced fibrosis were computed and cross-validated. In 90 children with mean age of 13.1 ± 2.4 years, median hepatic stiffness was 2.35 kPa. Stiffness values derived by each reading center were strongly correlated with each other (r=0.83). All three analyses were significantly correlated with fibrosis stage (center 1, ρ=0.53; center 2, ρ=0.55; and automated analysis, ρ=0.52; p<0.001). Overall cross-validated accuracy for detecting any fibrosis was the same for all methods: 72.2% (61.8 – 81.1). Overall cross-validated accuracy for assessing advanced fibrosis varied by method: 88.9% (80.5% – 94.5%) for center 1, 90.0% (81.9% – 95.3%) for center 2, and 86.7% (77.9 – 92.9) for automated analysis. Conclusions 2D-MRE can estimate hepatic stiffness in children with NAFLD. Further refinement and validation of automated analysis techniques will be an important step in standardizing MRE. How to best integrate MRE into clinical protocols for the assessment of NAFLD in children will need prospective evaluation.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease among children. Lifestyle interventions, such as diet and exercise, are frequently recommended. Children with NAFLD have a distinct physiology that is different from obesity alone and has the potential to influence lifestyle treatments. Studies of diet alone in the treatment of pediatric NAFLD have focused on sugar and carbohydrate, but did not indicate any one dietary approach that was superior to another. For children who are obese and have NAFLD, weight loss may have a beneficial effect regardless of the diet used. Exercise is widely believed to improve NAFLD because a sedentary lifestyle, poor aerobic fitness, and low muscle mass are all risk factors for NAFLD. However, there have been no randomized controlled trials of exercise as a treatment for children with NAFLD. Studies of the combination of diet and exercise suggest a potential for improvement in serum alanine aminotransferase activity and/or magnetic resonance imaging liver fat fraction with intervention. There is also enthusiasm for the use of dietary supplements, however, studies in children have shown inconsistent effects of vitamin E, fish oil, and probiotics. This review presents the available data from studies of lifestyle intervention and dietary supplements published to date, and highlights challenges that must be addressed in order to advance the evidence base for the treatment of pediatric NAFLD.

Children with zone 1 or zone 3 distribution of steatosis have an important subphenotype of pediatric NAFLD. Children with zone 1 steatosis are more likely to have advanced fibrosis and children with zone 3 steatosis are more likely to have steatohepatitis. To achieve a comprehensive understanding of pediatric NAFLD, studies of pathophysiology, natural history, and response to treatment should account for the zonality of steatosis.