Progressive Familial Intrahepatic Cholestasis (PFIC)

Progressive familial intrahepatic cholestasis (PFIC) is a group of rare genetic diseases in which the flow of bile from the liver is disrupted. Bile is a digestive liquid made by the liver. In children with PFIC, bile builds up in liver cells over time and causes progressive liver disease.

There are three types of PFIC: PFIC 1, PFIC 2, and PFIC 3. Each type is caused by a mutation in a different gene: ATP8B1, ABCB11, and ABCB4. A child must inherit two copies of a mutated gene (one from each parent) to have the disease.

Symptoms of PFIC usually begin in infancy and may progress quickly. However, some patients develop symptoms later in childhood. Nearly all children need treatment by early adulthood.

Children with PFIC may experience severe itchiness (called pruritus), poor growth, yellowing of the skin and whites of the eyes (called jaundice), an enlarged liver and spleen, and fatigue. Patients also may have difficulty absorbing fats and fat-soluble vitamins.

Some children with PFIC 1 also may have short stature, deafness, diarrhea, or inflammation of the pancreas (called pancreatitis).

Complications of PFIC that may occur over time include gallstones, liver failure, and liver cancer (also called hepatocellular carcinoma).

A patient is usually tested for PFIC when their liver test shows an abnormal result, especially high levels of bilirubin or bile salts/acids. One particular liver test, gamma-glutamyl-transferase (GGT), shows low levels in patients with PFIC 1 and PFIC 2 but high levels in PFIC 3. After finding abnormal GGT levels, your doctor may order genetic testing to determine the specific type of PFIC.

A liver biopsy can also help make a diagnosis. A liver biopsy is when a small piece of liver tissue is removed for testing with a small needle. Your doctor will also test for other causes of liver disease, such as Alagille syndrome, biliary atresia, infections, and alpha-1 antitrypsin deficiency, to rule them out.

Children with PFIC should be under the care of a pediatric gastroenterologist with expertise in liver disease. Routine monitoring of the child’s overall health and growth, liver enzyme values, and signs of advancing liver disease are essential to keep patients healthy.

Medical treatments include drugs that treat symptoms such as itchiness and that try to reduce bile formation or increase bile flow. Because most children with chronic liver disease may have difficulty absorbing certain vitamins (specifically vitamins A,D, E, and K) from their intestines, high-dose vitamin supplements are often prescribed. 

Itchiness is a problematic symptom that affects a child’s quality of life. Treatment with anti-histamines is often tried first. Other medications such as rifampicin and cholestyramine are also used to treat itchiness. A newer class of medications called IBAT inhibitors prevents absorption of bile acids from the intestine and can help reduce itching in some patients. In 2021, the FDA approved the drug odevixibat to treat itchiness in PFIC.    

Patients who do not respond to therapy and have significant itchiness may require surgery. Surgeries for children with PFIC include a partial external biliary diversion (PEBD) and/or a liver transplant.

PEBD is a surgery in which a piece of intestine is used as a channel to remove bile from the gallbladder through an opening in the skin. This surgery decreases the amount of bile acids in the liver, which can decrease itching and may delay the need for liver transplant. PEBD may be used in a patient without liver failure who does not respond to treatment.

Liver transplant is needed if a patient does not respond to PEBD or has liver failure. Liver transplantation can also improve growth failure and itchiness. If necessary, your gastroenterologist may refer your child to a liver transplant center. 

Authored by Saeed Mohammad, MD and Alisha Mavis, MD
Editor: Athos Bousvaros, MD
June 2021