Health Topics

Progressive familial intrahepatic cholestasis is caused by defects in several genes that produce proteins needed for bile formation and the "transportation" or flow of bile throughout the body.

Bile is a liquid produced in the liver that removes toxins from the body and helps break down fat in food. The bile ducts are important 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, damaging liver cells and causing a dangerous buildup of waste in the blood stream. Decreased bile flow also prevents the body from being able to properly absorb fats and vitamins.

Every person is born with many genes that make up the body and that are passed on to them (inherited) from their parents. Progressive familial intrahepatic cholestasis is an inherited condition and does not appear unless a person receives the same defective gene from both parents. If both parents carry an abnormal gene for progressive familial intrahepatic cholestasis there is: 

• A 25% chance their child will develop the disorder 
• A 50% chance their child will receive one defective gene from one of the parents, which means the child will not show symptoms of the disorder but is a "carrier" 
• A 25% chance their child will receive both normal genes, one from each parent, and will be unaffected

• 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: 

• Abnormal enlargement of the liver and spleen 
• Fatigue (tired all of the time) 
• Poor feeding, nausea and vomiting
• Complications that may arise include: 
• Difficulty absorbing fats and fat-soluble vitamins (D, E, A, K) 
• Failure to thrive 
• Cirrhosis within 5 to 10 years, with liver failure 
• Liver cancer 
• Gallstones in the gallbladder

In order to tell if a patient has progressive familial intrahepatic cholestasis, some tests need to be completed. 

• Liver function tests are blood tests used to assess the general state of the liver or biliary system 
• A nuclear scan may be done to show how much bile is flowing from the liver 
• A highly specialized test measuring bile salt levels may be done to pinpoint progressive familial intrahepatic cholestasis (The total bile salt concentration in individuals with progressive familial intrahepatic cholestasis 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 laboratory 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 have a more rapid progression to fibrosis, the forming of scar tissue 
• About three-fourths 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 3 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.

Some patients may respond to medical therapy, although surgical treatment is usually necessary for survival.

Surgical treatment used in children with progressive familial intrahepatic cholestasis includes liver transplantation for cirrhosis and partial external biliary diversion (PEBD).

Liver Transplantation

Liver transplantation may be used if partial external biliary diversion is ineffective or if the patient has liver cirrhosis. It is the only effective treatment of high-GGT PFIC.

Most progressive familial intrahepatic cholestasis disorders progress to end-stage liver disease and require liver transplantation. Treatment focuses on minimizing growth failure and decreasing discomfort as the child awaits liver transplantation. Survival rates for liver transplantation to treat progressive familial intrahepatic cholestasis are excellent.

Partial External Biliary Diversion (PEBD)

Partial external biliary diversion may be used as the first choice of treatment for patients who have not yet developed cirrhosis. This treatment helps reduce the circulation of bile acids in the liver in order to reduce complications and prevent the need for early transplantation in many patients.

This surgical technique involves isolating a segment 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 and the other end is brought out to the skin to form a stoma (a surgically constructed opening to permit the passage of waste).

Partial external biliary diversion is used for patients who are unresponsive to all medical therapy, especially older, larger patients. This procedure may not be of help to young patients such as infants. Partial external biliary diversion may decrease the intensity of the itching and abnormally low levels of cholesterol in the blood.

Medications to Treat Symptoms of Progressive Familial Intrahepatic Cholestasis

In most cases of progressive familial intrahepatic cholestasis, the biggest issue is pruritis (itching). Medicine may be used to to relieve the severe itching caused by a buildup of bile in the blood and skin and to improve bile flow.

Vitamin Supplements

Reduced bile flow can lead to difficulty digesting fat and vitamins from a child's diet. Fat-soluble vitamin supplements (A, D, E, and K) may be used.