Advances in pediatric nonalcoholic fatty liver disease

Abstract

Nonalcoholic fatty liver disease (NAFLD) has emerged as the leading cause of chronic liver disease in children and adolescents in the United States. A two- to three-fold rise in the rates of obesity and overweight in children over the last two decades is probably responsible for the NAFLD epidemic. Emerging data suggest that children with nonalcoholic steatohepatitis (NASH) progress to cirrhosis, which may ultimately increase liver-related mortality. More worrisome is the recognition that cardiovascular risk and morbidity in children and adolescents are associated with fatty liver. Pediatric fatty liver disease often displays a histologic pattern distinct from that found in adults. Liver biopsy remains the gold standard for diagnosis of NASH. Noninvasive biomarkers are needed to identify individuals with progressive liver injury. Targeted therapies to improve liver histology and metabolic abnormalities associated with fatty liver are needed. Currently, randomized-controlled trials are underway in the pediatric population to define pharmacologic therapy for NAFLD.

Conclusion: Public health awareness and intervention are needed to promote healthy diet, exercise, and lifestyle modifications to prevent and reduce the burden of disease in the community.

Figure 1

Panel A-D represent typical histologic pattern seen in children with type 2 NASH. Panel A and B shows absence of ballooning degeneration and peri-sinusoidal fibrosis in the presence of steatosis and portal inflammation. Panel C demonstrates portal fibrotic expansion and marked steatosis. Panel D shows peri-portal inflammation without steatosis in zone 1 (around portal tract) and mild portal fibrosis in the absence of any fibrosis in zone 3 (around central vein). Reproduced with permission from Hepatology (Schwimmer JB, Behling C, Newbury R, Deutsch R, Nievergelt C, Schork NJ, Lavine JE. Hepatology. 2005 Sep;42(3):641-9)

Figure 2

Panel A. 15 year old boy with cirrhosis due to NASH. Shown are source images obtained at 3T with echo times of 1.15, 2.3, 3.45, 4.6, 5.75, and 6.9 msec; fat fraction map derived from the source images with T2* correction and spectrum modeling showing the percentage of fat in different portions of the liver; and double-contrast enhanced MR image depicting fibrotic reticulations throughout the liver, most pronounced in the periphery. Panel B. 16 year old boy with NASH. Shown are fat fraction maps from a 2-point Dixon technique (estimated fat fraction 6%) and from a T1-independent, T2*-corrected, spectrum-modeled 6-point technique (estimated fat fraction 11%). Also shown are spectra acquired using STEAM at multiple echo times from 10 to 30 msec. T2-corrected fat-fraction measured by spectroscopy = 11%.

Figure 2

Panel A. 15 year old boy with cirrhosis due to NASH. Shown are source images obtained at 3T with echo times of 1.15, 2.3, 3.45, 4.6, 5.75, and 6.9 msec; fat fraction map derived from the source images with T2* correction and spectrum modeling showing the percentage of fat in different portions of the liver; and double-contrast enhanced MR image depicting fibrotic reticulations throughout the liver, most pronounced in the periphery. Panel B. 16 year old boy with NASH. Shown are fat fraction maps from a 2-point Dixon technique (estimated fat fraction 6%) and from a T1-independent, T2*-corrected, spectrum-modeled 6-point technique (estimated fat fraction 11%). Also shown are spectra acquired using STEAM at multiple echo times from 10 to 30 msec. T2-corrected fat-fraction measured by spectroscopy = 11%.