Health Library

Progressive Familial Intrahepatic Cholestasis (PFIC)

Normally, bile flows from liver cells into small tubes called bile ducts, and then into the intestine. But in PFIC, this flow is blocked or slowed down. When bile can’t drain properly, it builds up inside the liver. This buildup is toxic—it irritates and damages liver cells over time. Think of it like a clogged drain: if the waste can’t leave, it starts harming the system. That’s why PFIC can lead to serious liver damage and, in some cases, liver failure.

When doctors first discovered PFIC, they noticed that many children had similar symptoms—mainly problems with bile flow. As scientists learned more, they found that different genes were causing these problems. They named the types in the order they were discovered:

• PFIC1 is linked to the ATP8B1 gene (affects protein FIC1)
• PFIC2 is linked to the ABCB11 gene (affects protein BSEP)
• PFIC3 is linked to the ABCB4 gene (affects protein MDR3)

As genetic testing has improved, more PFIC types have been found in the past 10 years. Today, there are 13 known PFIC subtypes. The actual list of genes that have been connected to PFIC-like symptoms is even longer.

What Causes PFIC?

PFIC is caused by changes (mutations) in the part of DNA that codes genes. The altered (mutated) genes work to produce proteins needed to make and get rid of bile from the liver. The patient may have a form of PFIC if they inherited a mutation from one or both of their parents, or if a spontaneous mutation happened when the embryo was formed.

Each form of PFIC involves a specific gene, which affects a different protein, and then causes a different problem with bile formation or flow.

PFIC is a rare disorder that can be caused by a growing number of rare mutations, and patients often wait a long time to receive a diagnosis or remain undiagnosed. Our center for Undiagnosed and Rare Liver Disease has created the most comprehensive gene panel for genetic cholestatic liver disease that looks at 1447 genes to find new and very rare mutations.

What Are the Signs and Symptoms of PFIC?

The signs and symptoms of PFIC include:

• Severe itching (pruritus)
• Poor weight gain (due to a lack of bile needed to digest and absorb fat) and poor growth
• Jaundice (yellowing of the skin)
• Bleeding caused by vitamin K deficiency
• Poor bone growth caused by vitamin D deficiency
• Gallstones at a young age
• Intrahepatic cholestasis of pregnancy (ICP)

Other symptoms may include:

• Enlargement of the liver and spleen that is not normal
• Fatigue (tired all of the time)
• Poor feeding, upset belly and throwing up

Problems that may happen include:

• Problems absorbing fats and fat-soluble vitamins (A, D, E, K)
• Failure to thrive
• Cirrhosis within five to 10 years, with liver failure
• Liver cancer
• Gallstones in the gallbladder
• Intrahepatic chloestasis of pregnancy (ICP)

How is PFIC Diagnosed?

PFIC is usually diagnosed through a series of tests, including:

• Blood tests to look for injury of the liver or biliary system
• Ultrasound, CT scan or MRI to check the anatomy/structure of the liver or biliary system
• A liver biopsy to evaluate the pattern of injury to liver tissue
• Gene tests to determine if the patient has a mutation known to cause one of the forms of PFIC

If the genetic test is inconclusive and there is a strong suspicion for PFIC, a research study may be available to look more deeply at the patient’s DNA. A new gene mutation may be causing the symptoms, but is not yet known to cause PFIC. Scientists can study this in the lab and help determine if a genetic mutation is the cause of the liver disease. When your child is diagnosed with one of the sub-groups of PFIC, your healthcare provider will explain what is known about the disease course and how it may affect the body.

How is PFIC Treated?

Treatment focuses on helping children grow and develop as expected and decreasing discomfort.

Supplemental nutrition and fat-soluble vitamins are recommended. However, there are no drugs specifically approved to treat the persistent itching associated with cholestasis. Some patients may respond to non-specific (“off-label”) medical therapy.

Medical treatment focuses on symptom relief by using medications that can increase bile flow. A liver transplant may be needed for long-term survival.

Medicines to treat symptoms of PFIC

In most cases of PFIC, the biggest issue is pruritus (itching). Medicines may be used to relieve the most severe itching and to improve bile flow.

Vitamin Supplements

Reduced bile flow can lead to problems digesting fat and vitamins from a child's diet. Fat-soluble vitamin supplements (A, D, E and K) may be used.

Liver Transplant

A liver transplant may be needed if medications are not helping or if the patient has cirrhosis or complications of liver injury.

PFIC disorders may progress to end-stage liver disease and require a liver transplant. Survival rates for liver transplant to treat PFIC are excellent.