This project uses a cross-sectional design with a single testing period without a formal intervention (e.g., diet, drug, exercise) or natural follow-up period. Participants with nonalcoholic fatty liver disease (NAFLD), and age-matched control groups classified as either obese (Ob control) or normal weight (NW control) will complete all metabolic and descriptive tests, including blood analyses.~The NAFLD group will also have a liver biopsy as part of their standard clinical care; a portion of the biopsy will be used for the research testing. The Ob and NW control groups will not undergo liver biopsy. To provide a set of reference liver samples to compare with the NAFLD group, we will enroll a liver control group, consisting of age-matched patients who are scheduled to have a cholecystectomy with liver biopsy or are undergoing liver resection for tumor removal.
Nonalcoholic fatty liver disease (NAFLD) is now the most common liver disease worldwide and affects nearly 40% of obese youth and up to 10% of the general pediatric population. Some features of NAFLD are similar in children and adults, yet fibrosis and inflammation are more common in the portal zone and occur earlier in pediatric NAFLD patients than adults. This portends a rapid progression to end-stage liver disease in early adulthood. For the majority of children with NAFLD, mechanisms driving the origin and rapid progression of disease remain unknown. Thus, there is a critical, unmet need to study the specific underlying patterns of metabolic and molecular changes in the liver underlying the development and progression unique to children with NAFLD.~This proposal will test the hypotheses that children with NAFLD have excess glucose and lipid produced by the liver, that those events are regulated by specific variations in the amount and location of RNAs and proteins in liver, and that the concentration of specific micro-RNAs in the blood can be used as a biomarker for NAFLD in pediatric patients.