PFIC (Progressive Familial Intrahepatic Cholestasis)
What is Progressive Familial Intrahepatic Cholestasis (PFIC)
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 should be put into bile.
The symptoms of PFIC
FIC1 and BSEP disease cause similar symptoms; together they are called low-GGT PFIC because of a blood test (GGT) that is low rather than high as in most other forms of cholestasis.
These diseases cause cholestasis that begins in early childhood, with the average age at onset being 3 months. However, some patients do not get symptoms of cholestasis until they are teenagers or young adults. These diseases can progress quickly to bad scarring of the liver (cirrhosis) in the first year of life or more slowly with minimal scarring well into the teenage years. Few patients have survived beyond 20 years without treatment.
Itching (pruritus) is the main symptom of cholestasis in many patients. Pruritus is often out of proportion to the level of jaundice (yellow eyes or skin), which is often low-grade and can wax and wane. Scratching starts as digging at the ears and eyes, which are the first areas to show bleeding and scarring. The itching may be very disabling and does not usually respond to medications. The scratching interferes with normal activities and sleep and may interfere with learning and schoolwork.
Problems with growth are another major feature of PFIC. Almost all patients are short for their age, but they may not be thin. Delayed puberty and sexual development is common. Patients who are treated can have normal sexual development and several have given birth to normal children.
Other common problems include frequent nosebleeds and wheezing. Fat-soluble vitamin (A, E, D and K) deficiencies are common in untreated patients.
Vitamin A deficiency can lead to problems with vision.
Vitamin E deficiency can lead to problems with balance, strength and coordination. Vitamin D deficiency can lead to poor bone formation.
Vitamin K deficiency can lead to bleeding problems. For these reasons, most patients need extra vitamins. Up to a third of patients have gallstones. Most patients have an enlarged liver or enlarged spleen.
Although similar, there are differences between patients with BSEP disease and those with FIC1 disease. For example, patients with FIC1 disease are more likely to have watery diarrhea, which can be severe, especially after liver transplantation. However, there is much that we do not yet know about these differences and this will only become clear as more patients are studied.
Patients with PFIC but with high serum GGT have been called PFIC3, and are now called MDR3 disease. These patients have very bad cholestasis in the first year of life, which may progress in the first few years of life toward failure of the liver to do its normal functions. However, there are probably less severe forms of MDR3 disease that cause milder disease. The child and his family may first become aware that there is something wrong during school age or adolescence. Sometimes, problems may not appear until adulthood. The full spectrum of liver problems caused by MDR3 disease is just now becoming known.