Nonalcoholic fatty liver disease (NAFLD) is an obesity associated chronic liver disease that is the most common liver disease in adolescents today. It is closely associated with the metabolic syndrome and dyslipidemia. Research suggests that adolescents with NAFLD will be at substantial risk of increased morbidity in the future from both cardiovascular disease and end stage liver disease unless effective therapies are developed to change this trajectory. While lifestyle changes can improve histology and CVD risk, many patients are unsuccessful at sustained weight loss. Thus, medications to treat CVD risk and liver inflammation, steatosis and fibrosis in NAFLD are critically needed. We have been studying adolescents with NAFLD and have pilot data linking inflammatory mechanisms in NAFLD and increased CVD risk. Angiotensin receptor blockers (ARB) have been proposed as a novel treatment of NAFLD in part because they would treat both the factors increasing CVD risk as well as potentially improve steatosis, fibrosis and hepatic inflammation. Losartan, an established ARB has demonstrated significant potential in animal models and limited pilot studies in adults with NAFLD have been promising. However, no data exists on the effects of losartan in children with NAFLD. We propose a 26 week pilot study in adolescents with NAFLD to test if losartan will improve non-invasive markers of CVD risk and liver steatosis, inflammation and fibrosis. This proposal is highly innovative because an ARB has not previously been tested in adolescents with NAFLD and because novel markers of CVD risk will be tested in addition to the typical markers. This study is highly significant because NAFLD is the most common liver disease among children today and is associated with substantially increased risk of CVD and increased mortality as these adolescents age into adulthood.
Nonalcoholic fatty liver disease is estimated to affect up to 30% of overweight children in the US, making it the most common liver disease in children. Natural history studies demonstrate that NAFLD leads to increased mortality from both cardiovascular disease and end stage liver disease. This project will develop pilot data for a new potential therapy to target hepatic effects of NAFLD and to decrease the associated cardiovascular disease risk. If this therapy is effective, this will improve the long term health o millions of children and prevent this increased mortality.
|Jin, Ran; Banton, Sophia; Tran, ViLinh T et al. (2016) Amino Acid Metabolism is Altered in Adolescents with Nonalcoholic Fatty Liver Disease-An Untargeted, High Resolution Metabolomics Study. J Pediatr 172:14-19.e5|
|Holzberg, Jeffrey R; Jin, Ran; Le, Ngoc-Anh et al. (2016) Plasminogen Activator Inhibitor-1 Predicts Quantity of Hepatic Steatosis Independent of Insulin Resistance and Body Weight. J Pediatr Gastroenterol Nutr 62:819-23|
|Jin, Ran; Le, Ngoc-Anh; Cleeton, Rebecca et al. (2015) Amount of hepatic fat predicts cardiovascular risk independent of insulin resistance among Hispanic-American adolescents. Lipids Health Dis 14:39|
|Vos, Miriam B (2015) Is it time to advance pediatric NAFLD diagnosis to the magnetic resonance imaging era? Hepatology 61:1779-80|
|Jin, Ran; Welsh, Jean A; Le, Ngoc-Anh et al. (2014) Dietary fructose reduction improves markers of cardiovascular disease risk in Hispanic-American adolescents with NAFLD. Nutrients 6:3187-201|