Combined computational fluid dynamic and metabolic model of liver defatting under flow

Macrosteatotic livers have become endemic in our nation as obesity continues to rise, consequently leading to a decrease in the number of viable transplantable livers in the donor pool. Considering orthotopic liver transplantation has been proven to be the most effective cure for liver failure caused by macrosteatotic livers, it is imperative a method be developed in order to recondition livers into their lean, fully functioning form for transplant. Prior research groups have shown that metabolic preconditioning is a viable option for liver defatting. Others used computational work to explain the importance of oxygen and an accurate liver geometry. In our laboratory, we have experimentally shown that we can reduce the degree of macrosteatosis in the liver. However this approach is limited because the kinetics of defatting currently exceed the therapeutic window in terms of liver transplantation. We wish to develop a novel computational fluid dynamic model coupled with a kinetic model of hepatocyte metabolism to identify key rate limiting pathways inherent in lipid droplet breakdown and removal within hepatocytes. Currently, our model includes key physiological aspects of the liver such as flow rate, oxygen concentration and distribution, and robust metabolic and cellular-transport models. This model, upon experimental validation, will provide a screening tool to optimize defatting protocols and reagents to develop a clinical protocol which will reduce macrosteatosis in marginal donor organs to allow for pre-conditioning within a therapeutic time-frame.