Progressive familial intrahepatic cholestasis (PFIC) is a rare inherited condition. In PFIC children are not able to drain bile from the liver even though the large bile ducts are open (cholestasis). Bile acid builds up in liver cells. This can lead to jaundice, severe itching and malabsorption. This gets worse over time.

PFIC is the result of a gene change (mutation). There are a few different type of gene mutations that can cause PFIC. Each change has different effects on the body. In some of the changes, the liver, lung, intestine and ears can be affected.

Most children with PFIC end up with cirrhosis (scarring) of the liver and end-stage liver failure. They need to have a liver transplant. When performed by an experienced team of specialists, liver transplantation for PFIC can improve a child’s quality of life and lessen their symptoms.

Children with PFIC who need a liver transplant can receive a whole liver from a deceased donor. Or they may receive a segment of a liver from a living donor. Both types of transplants are available from the expert liver transplant team at Cincinnati Children’s.

Causes

PFIC is a term used to designate a group of inherited diseases, caused by changes (mutations) or 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 develop a form of PFIC if they have an altered gene.

Bile is a liquid made in the liver that removes toxins and waste from the body. Bile is also important in digesting fat in foods in the intestine.

A blockage of bile in the liver or bile ducts causes toxins in bile remain in the body. This damages liver cells. It causes a harmful buildup of waste in the blood stream. Decreased bile flow also prevents the body from being able to properly digest fats and vitamins.

As mentioned above, the term PFIC refers to a group of inherited diseases. This means that it happens due to genes that are passed on (inherited) from parents. PFIC does not develop unless a person receives the same type of mutated gene from both parents. If both parents carry a gene for PFIC, there is:

• A 25% chance their child will develop the disorder.
• A 50% chance their child will receive one mutated gene from one of the parents. This means the child will not show symptoms of the disorder but is a "carrier".
• A 25% chance their child will receive both non-mutated genes, one from each parent. They will not be affected.

Signs and Symptoms

• 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

Other symptoms may include:

• Enlargement of the liver and spleen
• Fatigue
• Poor feeding, throwing up, diarrhea

Problems that may arise include:

• Problems absorbing fats and fat-soluble vitamins (D, E, A, K)
• Failure to grow
• Cirrhosis within five to 10 years, with liver failure
• Liver cancer
• Gallstones

Diagnosis

The typical series of tests to be done include:

• Blood tests to look for injury of the liver or biliary system
• Ultrasound, CT scan or MRI to assess 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

There are several types of PFIC. Different genes have been found to cause slightly different types of PFIC. When your child is diagnosed with one of the types of PFIC, your doctor will explain what is known about disease course of PFIC and how it affects the body.

Treatment

Treatment focuses on minimizing growth failure and decreasing discomfort.

Supplemental nutrition and fat-soluble vitamins are recommended. However, there are no drugs specifically approved for the management of the persistent itching associated with cholestasis. Some patients may respond to non-specific medical therapy.

Medical treatment strategies target symptomatic relief with use of medications that can increase bile flow. These medications can also give some relief of symptoms. A liver transplant may be needed for a long-term survival.

Medicines to Treat Symptoms of Progressive Familial Intrahepatic Cholestasis

In most cases of PFIC, the biggest issue is pruritus (itching). Medicine may be used to relieve the 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 used if medications are not effective 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.

Cincinnati Children’s has one of the largest and oldest pediatric liver transplant programs in the United States. The team offers an improved survival rate compared to the national average for transplant centers. Cincinnati Children’s patients experience shorter average times on the transplant waitlist.

• The median wait time for a new liver at Cincinnati Children’s is 3.7 months, compared to the national median wait time of 8.7 months.
• 66.2% of our patients receive a transplant within one year of wait listing, compared to 48.5% nationally.