Hormonal Imbalance in Morbidly Obese Bariatric Patients with Liver Steatosis and Non-alcoholic Steatohepatitis (nash)

HORMONAL IMBALANCE IN MORBIDLY OBESE BARIATRIC PATIENTS WITH LIVER STEATOSIS AND NON-ALCOHOLIC STEATOHEPATITIS (NASH) Massih Abawi, Ph.D George Mason University, 2015 Dissertation Director: Dr. Ancha Baranova Non-alcoholic fatty liver disease (NAFLD) is an increasingly common condition affecting about 70% of obese individuals and is now considered a major cause of liver-related morbidity and mortality. NAFLD encompasses a spectrum of hepatic pathologies with excessive accumulation of fat in the liver in patients consuming less than 20 grams of alcohol per day. NAFLD related liver injury ranges from simple hepatic steatosis to more severe forms of the disease including NASH, which can progress to fibrosis, cirrhosis, and ultimately organ failure. There is evidence that causally links NAFLD with imbalance of various hormones, especially these also involved in the development of insulin resistance and obesity. The research presented herein involves quantitation of various soluble hormones in serum of morbidly obese bariatric patients with different confirmed stages of NAFLD. The first study explores the role of vitamin D deficiency in NAFLD/NASH patients. Serum samples of 210 morbidly obese bariatric patients were profiled for the following markers: 25(OH)D3; Vitamin D Binding protein (VDBP); Intact Parathyroid Hormone (1-84) and Cytokeratin 18 (M30) levels. The second study herein profiles three small gastric peptides, acylated ghrelin (AG), non-acylated ghrelin (DAG), and Obestatin, and a number of proinflammatory cytokines in circulation of patients with obesity related NAFLD. In both studies, correlation analysis was conducted to associate these biomarkers with clinical parameters routinely measured in NAFLD patients, including histological scores of inflammation and fibrosis of their liver biopsies, and predictive regression models were built. A third study reported herein investigates the interplay of circulatory melanogenesis-related hormones, αMelanocyte Stimulating Hormone (α-MSH) and Melanin Concentrating Hormone (MCH), with NAFLD and obesity-induced low grade chronic.