Progressive Familial Intrahepatic Cholestasis (PFIC) comprises a group of rare, severe liver diseases in children. Different types of PFIC have been identified, based on loss-of-function mutations in several genes involved in bile formation, leading to bile acid-induced liver damage. Patients with PFIC develop progressive deterioration of liver function that frequently evolves in the need for liver transplantation. The treatment of patients with PFIC diseases has long been largely symptomatic, but more recently major progress has been made. Medical therapies have been developed that target bile acid homeostasis, such as via interruption of the enterohepatic circulation (Apical Sodium-dependent Bile acid Transporter inhibitors, or ASBTi). In 2017, the NAtural course and Prognosis of PFIC and Effect of biliary Diversion (NAPPED) registry was launched, and in 2023 the TreatFIC registry. These registries have created the opportunity to investigate rare liver diseases in a large patient population. Since their start, these registries have become global networks focusing on increasing our understanding the pathophysiology and improving the treatment strategies of PFIC diseases. The registries are still expanding in number of global centers that contribute to the registries and in number of patients included in the registries.
Within the present PhD project you will address further personalization on predictability of disease course and responsiveness to treatments, including ASBTi, in different types of PFIC. You will maintain and expand the NAPPED and TreatFIC registries and will apply epidemiological methods to determine detailed genotype-phenotype relationships and responses of ASBTi treatment on disease course. Within this PhD project you have a major contribution towards personalized treatments for PFIC diseases. You will work in a team consisting of PhD-students, post-docs and technicians that are supervised by principal investigators, in collaboration with Prof. Bettina Hansen (Epidemiology, Erasmus Medical Center, Rotterdam).