PFIC is a rare genetic disorder that causes progressive liver disease that may start early after birth or at a young age and rapidly progress to end-stage liver disease.
The most prominent and problematic ongoing manifestation of PFIC is pruritus, which leads to a severely diminished quality of life. PFIC has been estimated to affect between one in every 50,000 to 100,000 births worldwide. Based on those estimated incidences, we project there are 3,000 children with PFIC in the United States and 10,000 in the European Union.
PFIC leads in many cases to cirrhosis and liver failure within the first 10 years of life, and nearly all children with PFIC will require treatment before age 30. There are no medicines currently approved for PFIC, only surgical options – including a procedure known as Partial External Biliary Diversion (PEBD) or liver transplantation. These options carry substantial risk of post-surgical complications, as well as psychological and social issues.
Three alternative gene defects have been identified that correlate to three separate PFIC subtypes known as PFIC, type 1, PFIC, type 2, and PFIC, type 3. There may also be other gene defects that give rise to additional PFIC subtypes.
- PFIC, type 1, which is sometimes referred to as “Byler disease,” is caused by impaired bile secretion due to mutations in the ATP8B1 gene, which codes for a protein that helps to maintain an appropriate balance of fats known as phospholipids in cell membranes in the bile ducts. An imbalance in these phospholipids is associated with cholestasis and elevated bile acids in the liver. Children affected by PFIC, type 1 usually develop cholestasis in the first months of life and, in the absence of surgical treatment, progress to cirrhosis and endstage liver disease before the end of the first decade of life.
- PFIC, type 2, which is sometimes referred to as “Byler syndrome,” is caused by impaired bile salt secretion due to mutations in the ABCB11 gene, which codes for a protein, known as the bile salt export pump, that moves bile acids out of the liver. Children with PFIC, type 2 often develop liver failure within the first few years of life and are at increased risk of developing a type of liver cancer known as hepatocellular carcinoma.
- PFIC, type 3, which typically presents in the first years of childhood with progressive cholestasis, is caused by mutations in the ABCB4 gene, which codes for a transporter that moves phospholipids across cell membranes.