Amino Acids and Pediatric Hepatic Steatosis

7. Project Summary/Abstract Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in North America (1). Hepatic steatosis (HS) is the hallmark of NAFLD (2). NAFLD may transition in sub-groups to chronic inflammation (non- alcoholic steatohepatitis, NASH), and ultimately to cirrhosis. HS is prevalent in all stages of NAFLD. 3-10% of all children in the US and 40-70% of obese children have HS (3). There are approximately 15 million obese children in the US (4), meaning that as many as 10 million youths have HS. Pediatric HS is associated with premature mortality due to type 2 diabetes (T2D), cardiovascular disease (CVD) and progressive liver disease in early adulthood (5,6). Successful treatment of pediatric HS is therefore central to long-term metabolic and cardiovascular health. Recommended options are largely limited to behavioral modifications (i.e., weight loss and exercise) and nutritional supplement with Vitamin E (3,5-7). There is no FDA-approved drug for the treatment of NAFLD in individuals of any age. We propose to perform a randomized clinical trial (RCT) in youths with HS. We will expand our previous study in which treatment with our essential amino acid (EAA)-based composition called AMS2392 reduced liver fat in adolescent females with polycystic ovary syndrome (PCOS). Specific Aim 1. We will investigate the hypothesis that 8 weeks of treatment with AMS2392 will reduce liver fat in youths with HS. We will perform a double-blind RCT in 48 male and female youths 13 to 18 years of age (Tanner stage 4 or 5) with biopsy-documented HS. Liver fat content will be measured by magnetic resonance imaging (MRI) at the outset and after the eight-week intervention. Specific Aim 2. We propose that secondary end points of liver stiffness, body composition, insulin sensitivity, and plasma concentrations of very-low density triglycerides (VLDL-TG), alanine transaminase (ALT), ApoB100, creatinine and insulin sensitivity will be improved in the group receiving AMS2392 as compared to placebo. Specific Aim 3. Adherence to protocol will be greater than 90% and there will be no adverse events in those consuming AMS2392, including no change in plasma glutathione concentration. Completion of this RCT will provide information regarding efficacy, effect size, safety and tolerance that will position us to successfully market AMS2392 as a medical nutrition product.