Mitochondrial Respiration in People with NAFLD and Cirrhosis

It is hypothesized that platelets of patients with advancing NAFLD (non alcoholic fatty liver) exhibit mitochondrial dysfunction which is associated with the severity of liver disease and with platelet activation. In this study we will specifically measure intact platelet mitochondrial respiration as a measure of mitochondrial dysfunction and compare results in matched patients with NAFLD at varying levels of disease severity (based on histology, liver stiffness, Child-Pugh score, and MELD score). To further test the novel and potentially disruptive hypothesis, we will examine if the platelet respiratory control ratio correlates with platelet activation: glycoprotein (GP) IIb/IIIa expression, PS externalization, and increased thrombin generation in response to adenosine diphosphate, arachidonic acid, and thrombin stimulation on thromboelastography in these patients. The research plan will examine the overall procoagulant profile, platelet mitochondrial respiration, platelet activation, and ROS generation, linked to results of thromboelastography in patients with NAFLD of varying severity, and results will be compared with age, gender, and BMI matched controls.