Progressive Familial Intrahepatic Cholestasis (PFIC)

PFIC Type 1

• Presents in the first months of life with cholestasis (impaired bile flow/formation) and yellowing of the skin (jaundice). Jaundice is recurrent and becomes permanent later in life. Individuals will often suffer from severe itching (pruritus), which is often said to have the greatest impact on quality of life.  Other characteristics may include short stature, deafness, diarrhea, and pancreatitis.

PFIC Type 2

• Presents with a more rapid course to liver failure. Those with PFIC Type 2 will present with cholestasis and more severe and permanent jaundice in the first months of life. Liver failure often appears within the first years of life with the potential for early liver cancer (hepatocellular carcinoma) to appear before 1 year of age. These individuals will also often experience severe pruritus.

PFIC Type 3

• Cholestasis appears in the first year of life, later infancy, or childhood/young adulthood. Those who do not have symptoms until adolescence or young adulthood may initially present with gastrointestinal bleeding, portal hypertension, or cirrhosis (chronic liver disease). Other symptoms may include mild to moderate pruritus.

Since PFIC is a rare group of diseases, more common liver diseases must be excluded first.

Lab Tests

• Liver tests (e.g. GGT, serum bile acid concentrations) can assist in the diagnosis of PFIC but will not confirm the diagnosis
• Other tests may include: PT, INR, total bilirubin

Imaging/biopsy

• Ultrasound
• MRCP
• Liver biopsy

Genetic Testing

• Can confirm the diagnosis and subtype of PFIC

The goals for managing PFIC include managing the itching (since this symptom can greatly impact the individuals’ and their families’/caregivers’ quality of life), managing vitamin deficiency and diet, and delaying time to liver transplant.

Managing the itching (or pruritus) can include basic care or medication.  Basic care may include regular use of moisturizing and cooling creams/gels (e.g. products containing 1-2% menthol), showering with cold water, keeping fingernails shortened, wearing light clothes made from natural fibers (e.g. cotton), avoiding scented detergents, and ruling out other medications causing the itching (known as drug-induced pruritus). Medications can be used to treat the pruritus in cholestatic liver diseases. Cholestyramine is the only FDA-approved medication for cholestatic pruritus. There are several other medications used for pruritus but have not been approved by the FDA for that indication.

Improving the nutritional status in those with PFIC is important.  This may include use of medium chain triglycerides (MCT), which is a form of fat that is better absorbed in those with cholestasis, regular monitoring of vitamin A, D, E, and K levels, as well as supplementing those vitamins as directed by a physician.  Appropriate calcium intake and sunlight exposure are also important for the absorption of certain vitamins.

Surgical interventions for PFIC may include:

• Partial external biliary diversion (PEBD), partial internal biliary drainage (PIBD), ileal bypass (IB), or liver transplant

Until recently, there has been no FDA-approved treatment for PFIC.  Ursodeoxycholic acid has been used off-label in PFIC patients, but its FDA approved indications are for the treatment of gallstones and primary biliary cholangitis. A new therapeutic option, odevixibat, is an oral ileal bile acid transporter inhibitor (IBATi) indicated for the treatment of PFIC. Through this mechanism, odevixibat will be able to stop bile acids from being reabsorbed from the small intestine back to the liver and reduce symptoms of pruritus and slow the progression of liver damage.