Progressive familial intrahepatic cholestasis (PFIC)

What is PFIC?

Progressive familial intrahepatic cholestasis (PFIC) is the term given to a group of inherited conditions that cause cholestasis (reduced bile flow) in children and young people. PFIC causes progressive liver disease that can result in liver failure.

Cholestasis can occur for a number of reasons including damaged bile ducts, not being able to make bile properly in the liver or an inability to get the bile out of the liver cells (hepatocytes) into the bile ducts. The build up of bile in the liver causes liver damage and can lead to liver failure.

PFIC is a genetic condition where a gene is mutated (changed) so it cannot make the normal protein needed for the liver to function properly. The mutated gene is inherited (passed on) from parents to children, and the child must receive a mutated gene from both the mother and the father in order to develop PFIC. There are three known types of PFIC: PFIC1, PFIC2 and PFIC3, each with a different genetic cause.

PFIC is estimated to affect between 1 in 50,000 and 1 in 100,000 people worldwide. The Children's Liver Disease Foundation has useful insights from those affected by PFIC.

Symptoms

Signs and symptoms of PFIC vary in type and severity and typically begin in infancy as bile begins to build up in the liver. Symptoms may include jaundice (a yellow discolouration of the skin, whites of the eyes, and possibly teeth); darker urine; deficiencies of fat-soluble vitamins A, D, E and K, a failure to grow and thrive; or pruritus (severe itching of the skin). Pale, white or grey stools, which may be loose, can also be a sign of liver disease and The Children's Liver Disease Foundation (CLDF) have a stool chart that can be used to compare your babies stools with healthy and potentially unhealthy stools.

Each type of PFIC may present with different symptoms:

PFIC1

• In addition to the liver disease-related symptoms, PIFC1 can affect the intestines, lungs and ears with affected individuals experiencing deafness, diarrhoea, short stature or pancreatic inflammation. Affected individuals with PFIC typically develop liver failure before adulthood.

PFIC2

• Affected individuals usually have more severe liver disease-related symptoms and often develop liver failure within the first few years of life. PFIC2-affected individuals also have an increased likelihood of developing hepatocellular carcinoma (a type of liver cancer).

PFIC3

• Most individuals affected by PFIC3 only have symptoms relating to liver disease, and these usually present later in infancy or early childhood; or rarely in adulthood. Liver failure may occur in childhood or adulthood in PFIC3-affected individuals.

Diagnosis

A variety of tests are usually performed to diagnose PFIC including:

• Physical examination
• Blood tests
• Urine tests
• Liver biopsy
• Abdominal ultrasound to check for an enlarged liver
• MRI to scan internal organs including bile ducts

Other paediatric liver diseases have similar symptoms to PFIC, so once cholestasis is confirmed other tests such as genetic testing may be performed to help with the PFIC diagnosis.

Treatment

Dietary treatment:

• Cholestasis can cause incomplete absorption of normal fats and fat soluble vitamins contributing to poor growth and loose stools. Supplements of MCT (medium chain triglycerides), a form of fat that is absorbed easier in cholestasis, can be used in children, or as part of a special formula in infants. Monitoring and supplementation of fat-soluble vitamins is also important to combat deficiencies.

Medical therapy:

• Certain medications can assist in relieving symptoms of PFIC, such as ursodeoxycholic acid (a helpful bile acid) treatment which may improve some mild forms of PFIC, however severe disease does not usually improve with medical therapy.

Surgical procedures:

• Surgical procedures have had some success in reducing the effects of PFIC, and a medical team may recommend a surgical option after assessing the patient.

• A partial external/cutaneous biliary diversion is a type of surgery (only suitable for patients without cirrhosis) that diverts bile from the gallbladder into a bag outside the body. Another surgery, limited ileal exclusion, creates a surgical bypass of the last part  of the small intestine and diverts bile salts to the colon where they are not absorbed. These types of surgery have been shown to improve pruritus and slow the progression of liver disease.

• If the patient does not improve with surgical intervention, if liver failure develops or if there is evidence of liver cancer, then liver transplantation may be required. Following the surgery additional medication is required to prevent the immune system from rejecting the new liver along with other medications such as antibiotics or blood pressure medicines.