Funding outcome

Progressive familial intra hepatic cholestasis type 2 (PFIC-2) is caused by mutations in a protein called ABCB11. This protein is only present in the liver and acts as a pump to help liver pump bile salts into the bile. Bile salts are made in the liver and pumped to the bile. After food intake, bile salts are released into the intestine to help digest fat in food. Mutations in ABCB11 damage the function of the protein, causing buildup of bile salts in the liver. Bile salts have detergent properties. Thus, accumulation of bile salts causes liver damage, leading to PFIC-2. PFIC-2 starts in infancy and often leads to liver failure or liver cancer before adulthood. Currently, PFIC2 is incurable. Certain treatments can relieve clinical symptoms and slow the progression of the disease. However, liver transplantation is ultimately needed for more than half of PFIC-2 patients. It has been reported that different mutations in ABCB11 damage different properties of the protein. Some mutations make ABCB11 unstable, while others make the protein stay in a wrong place in the liver cells. Different PFIC-2 patients normally carry different ABCB11 mutations. Several lines of evidence show that PFIC2 patients carrying specific mutations in ABCB11 respond well to specific treatment. Currently, we diagnose and treat PFCI patients in our clinic mainly based on symptoms. This approach cannot provide information essential for treatment of patients with PFIC2 in an accurate and effective way. Thus, to improve health outcomes of these patients and limit adverse effects of certain unnecessary approaches, the need for identification and characterization of ABCB11 mutation in patients with PFIC2 is clear and urgent.