What is PFIC?

The name PFIC was coined in the early 1980’s to describe a form of liver disease that primarily affects children. Taken word for word, it means: Progressive: tending to get worse over time; Familial: passed down to a child from the parents by way of the genes; Intrahepatic: involves disease inside the liver and not the bile ducts outside the liver; Cholestasis: means poor bile flow and build-up of substances in the liver that would normally be carried out of the liver into bile.  

A number of medical terms have been used to describe PFIC patients. “Byler’s disease” was used for Amish children with PFIC, in whom “PFIC” was first identified. Three types of PFIC have been labeled as PFIC-1, PFIC-2 and PFIC-3, although since we now understand these conditions at a genetic level, these terms are being used less and less. In recent years, it has been discovered that many patients with PFIC have mutations in one of three genes named ATP8B1, ABCB11, and ABCB4 

Mutations in these genes lead to a failure to make normal versions of these proteins and thereby cause PFIC in many patients. As a result, we think of PFIC as a family of diseases that look very similar but have different genetic causes. Thus PFIC-1 is referred to as FIC1 (familial intrahepatic cholestasis 1) deficiency or ATP8B1 deficiency, PFIC-2 is referred to as BSEP (bile salt export pump) deficiency or ABCB11 deficiency, and PFIC-3 as MDR3 (multidrug resistance-associated protein 3) deficiency or ABCB4 deficiency. Recently, a new gene, TJP2, has been implicated in patients with PFIC, and other “PFIC genes” are suspected to exist, because in some patients with clinical PFIC no mutations in ATP8B1, ABCB11, ABCB4, or TJP2 can be identified. 

Many individual specific genetic mutations lead to these diseases. Mutations that lead to a protein that is not formed or does not function result in severe disease. Some mutations lead to partially functional proteins. In general the disease associated with these mutations is milder and can even be intermittent in nature. However, even siblings with the same set of “PFIC gene” mutations can have widely differing clinical courses, probably because other parts of their genetic backgrounds are not identical. The intermittent forms of these diseases are often referred to as BRIC, which stands for benign recurrent intrahepatic cholestasis. (Of course it is not truly “benign”. During bouts of jaundice and itching, BRIC patients are miserable.) In addition, a child with BRIC may, as time passes, become a child with PFIC, whose cholestasis-free periods grow shorter and at last disappear. In short, even with genetic information in hand, to predict in detail how these deficiencies will evolve in a particular child is not really possible.