Other names: PFIC

Progressive familial intrahepatic cholestasis (PFIC) is a rare genetic disorder that worsens over time to cause liver disease, which can be life-threatening. Patients with PFIC have impaired bile flow (cholestasis), and the resulting bile build-up in liver cells causes liver disease and subsequent severe and debilitating itching (pruritus).

There are several different subtypes of PFIC involving different genetic mutations. The more common types of PFIC include:

• PFIC1 (FIC 1 deficiency) - mutations in the ATP8B1 gene, which causes deficiency of the FIC1 protein.
• PFIC2 (BSEP deficiency) - mutations in the ABCB11 gene, which causes deficiency of the Bile Salt Export Pump (BSEP) protein.
• PFIC3 (MDR3 deficiency) - mutations in the ABCB4 gene, which causes deficiency of the MDR3 protein.

PFIC1 and PFIC2 usually appear in the first months of life. PFIC3 may occur later in infancy, childhood, or young adulthood.

Symptoms of progressive familial intrahepatic cholestasis include intense itching, jaundice, poor weight gain, and slowed growth. PFIC can lead to cirrhosis and liver failure within the first 10 years of life.

Progressive familial intrahepatic cholestasis is diagnosed using several different tests including liver function tests, bile acid tests, liver biopsy, and genetic testing.

Some treatments may help, depending on the severity and types of symptoms, and the subtype of PFIC. Some mild forms of MDR3 deficiency (PFIC3) may respond well to ursodeoxycholic acid (ursodiol). Bylvay (odevixibat) is approved for the treatment of pruritus in patients aged 3 months of age and older with PFIC, but may not be effective in patients with BSEP deficiency (PFIC2).

Surgical treatments include partial external biliary diversion (PEBD), partial internal biliary diversion (PIBD), and liver transplantation.

Children with PFIC may need to receive infant formulas or supplements containing MCT (medium-chain triglycerides), a type of fat that is better absorbed in cholestasis. Levels of fat-soluble vitamins (A, E, D, and K) should also be monitored and supplements should be taken if needed.

Drugs used to treat Progressive Familial Intrahepatic Cholestasis