Progressive Familial Intrahepatic Cholestasis (PFIC)

Progressive Familial Intrahepatic Cholestasis (PFIC)

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). This gets worse over time. In recent years it was found that patients with PFIC have mutations in three genes, ATP8B1, ABCB11 and ABCB4. In some of the mutations, the liver, lung, intestine and ears can be affected.

This most often begins in infants less than 6 months of age and may get worse very quickly. But, some children start showing signs later, even as late as the teen years, and it progresses more slowly. Nearly all children with PFIC will need treatment before age 30.

Causes

PFIC is caused by defects in several genes. These genes produce proteins needed to form bile and to "transport" or keep the flow of bile throughout the body.

Bile is a liquid made in the liver that removes toxins from the body. It also helps break down fat in food. The bile ducts are vital because they carry bile out of the liver.

A blockage of bile in the liver or bile ducts means that toxins in bile remain in the body. This damages liver cells and causes a harmful buildup of waste in the blood stream. Decreased bile flow also prevents the body from being able to absorb fats and vitamins as it should.

Each person is born with many genes that make up their body. These genes are passed on to them (inherited) from their parents. PFIC is an inherited condition and does not appear unless a person receives the same flawed gene from both parents. If both parents carry a flawed gene for PFIC, there is: 

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

Signs and Symptoms

  • Severe itching caused by the buildup of bile salt in the body (pruritus) 
  • Poor weight gain (due to a lack of bile needed to digest and absorb fat) and poor growth 
  • Jaundice (yellowing of the skin)

Other symptoms may include: 

  • Enlargement of the liver and spleen that is not normal
  • Fatigue (tired all of the time) 
  • Poor feeding, upset belly, and throwing up

Problems that may arise include: 

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

Diagnosis

To tell if a patient has PFIC, some tests need to be done. 

  • Liver function tests are blood tests used to check the state of the liver or biliary system. 
  • Ultrasound, CT Scan or MRI may be done to check the liver or biliary system. 
  • A liver biopsy may be done to check the liver tissue.
  • A highly specialized test measuring bile salt levels may be done to pinpoint PFIC. The total bile salt concentration in people with PFIC is 10 to 20 times higher than the normal level.

Low-GGT PFIC (PFIC-1 and PFIC-2) is the term given to cases of PFIC in which lab tests show high levels of bilirubin and bile acids, but normal to low levels of the serum gamma-glutamyl-transferase (GGT).

PFIC-1 and PFIC-2 are two subgroups of low-GGT PFIC that have some differences: 

  • A different gene has been found to cause these slightly different forms of PFIC. 
  • The coarse, grainy bile found in PFIC-1 differs from the fine, threadlike bile in PFIC-2. 
  • Hepatitis (inflammation of the liver) in infants under 28 days old is more common in PFIC-2 patients. 
  • Patients with PFIC-2 lack one of the proteins which removes bile acids from liver cells and seem to progress quicker to fibrosis (the forming of scar tissue). 
  • About 75 percent of PFIC-2 patients develop fibrosis by age 2.

High-GGT PFIC (also called PFIC-3) refers to patients with high levels of bilirubin and bile acids and high levels of serum GGT (about three to 10 times what it should be). These patients tend to have more severe cholestasis in the first year and progress toward liver failure within the first few years of life.

Patients with PFIC-3 have a defect in one of the proteins which helps to remove phospholipids (a type of fat) from liver cells.

Treatment

Some patients may respond to medical therapy, but surgery is most often needed for survival.

Surgery methods used in children with PFIC includes liver transplant for cirrhosis and partial external biliary diversion (PEBD).

Liver Transplant

A liver transplant may be used if PEBD is not effective or if the patient has liver cirrhosis. It is the only effective treatment of high-GGT PFIC.

Most PFIC disorders progress to end-stage liver disease and require a liver transplant. Treatment focuses on minimizing growth failure and decreasing discomfort as the child waits for a liver transplant. Survival rates for liver transplant to treat PFIC are excellent.

Partial External Biliary Diversion (PEBD)

PEBD may be used as the first choice of treatment for patients who have not yet developed cirrhosis. This treatment helps reduce circulation of bile acids in the liver. This reduces problems and prevents the need for early transplant in many patients.

This surgery involves isolating part of intestine (10 cm long) for use as a biliary conduit (a channel for the passage of bile) from the rest of the intestine. One end of the conduit is attached to the gallbladder. The other end is brought out to the skin to form a stoma. A stoma is an opening made through surgery that allows waste to pass out of the body.

PEBP is used for patients who do not respond to all medical therapy, especially older, larger patients. This procedure may not be of help to young patients, such as infants. PEBP may decrease how intense the itching is and the abnormal, low levels of cholesterol in the blood.

Medicines to Treat Symptoms of Progressive Familial Intrahepatic Cholestasis

In most cases of PFIC, the biggest issue is pruritus (itching). This itching is caused by the buildup of bile in the blood and skin. 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.

Last Updated 12/2018