The role of the unfolded protein response (UPR) in pediatric cholestatic liver diseases

Study need/problem statement/Hypothesis: Cholestasis refers to any impairment to the flow of bile out of the liver into the digestive tract. Cholestasis can result from a blockage of bile flow by bile duct obstruction, but also may result from genetic diseases that affect the way that bile (including bile acids) is transported through liver cells. Several cholestatic liver diseases are more common in children than adults including biliary atresia, progressive familial intrahepatic cholestasis (PFIC), and Alagille syndrome. These cholestatic liver diseases cause liver failure and are the most common reason that children require liver transplants. Currently there are no effective medical treatments for these diseases and therefore liver transplant remains the only therapy for many children. In addition to the burden of transplantation, children with chronic cholestasis frequently suffer from many severe complications including malnutrition, poor growth, intense itching, severe vitamin deficiencies and fractured bones.