Progressive Familial Intrahepatic Cholestasis

Progressive familial intrahepatic cholestasis (PFIC) is a rare inherited condition caused by a mutation in a gene affecting the ability of bile to drain from the liver.

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symptoms: Learn about the symptoms of progressive familial Intrahepatic cholestasis, how to recognize them, and what to do if you experience them.
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what is progressive familial intrahepatic cholestasis?

Progressive familial intrahepatic cholestasis (PFIC) is a rare inherited condition that affects how the liver produces and secretes bile. In people with PFIC, liver cells are unable to move bile out of the liver effectively. As a result, bile builds up in the liver instead of reaching the small intestine, causing damage to liver cells and leading to progressive liver disease that can eventually result in liver failure. The buildup of bile may also enter the bloodstream, which can cause severe itching.

There are three main types of PFIC: PFIC1, PFIC2 and PFIC3. Each type of PFIC is caused by different genetic changes that affect bile transport in the liver. Over time, many people with PFIC develop significant liver scarring (fibrosis) and may progress to end-stage liver disease by adulthood. Because the disease is progressive, some individuals may ultimately require a liver transplant.

symptoms

PFIC symptoms begin in infancy
Failure to gain weight and grow at the expected rate
High blood pressure in the vein that supplies blood to the liver (portal hypertension)
Enlarged liver and spleen (hepatosplenomegaly)
Symptoms related to fat-soluble vitamin deficiencies such as fractures, dry skin, easy bleeding or bruising, and even nocturnal blindness.

Specific to PFIC1:

Short stature
Deafness
Diarrhea
Inflammation of the pancreas (pancreatitis)
Low levels of fat-soluble vitamins (A, D, E and K) in the blood
Affected individuals typically develop liver failure before adulthood

Specific to PFIC2:

Signs and symptoms are typically related to liver disease only, but tend to be more severe than those experienced by people with PFIC1
Develop liver failure within the first few years of life
Affected individuals are at increased risk of developing a type of liver cancer HCC

Specific to PFIC3:

Signs and symptoms are typically related to liver disease only
Signs and symptoms of PFIC3 usually do not appear until later in infancy or early childhood; rarely, people are diagnosed in early adulthood
Liver failure can occur in childhood or adulthood in people with PFIC3

Severe itching (cholestatic pruritus) is one of the main symptoms experienced by patients with PFIC. Pruritus, or itching, often follows a cycle: the urge to scratch provides temporary relief, but this is often followed by an intensification of itching in the same area, leading to more scratching. This cycle can become focused in specific areas and can be difficult to break.

lifestyle impacts

Progressive familial intrahepatic cholestasis generally affects infants and children causing patients to have difficulties growing and gaining weight, also known as failure to thrive. This can result in developmental delays, learning disabilities, and behavioral issues later in life.

what can I do?

prevention

Progressive familial intrahepatic cholestasis is an inherited disease and therefore cannot be prevented.

diagnosis

Diagnostic methods for progressive familial intrahepatic cholestasis include:

Clinical evaluation: detailed medical history, physical examination, and symptoms related to liver disease are important for diagnosis. Early symptoms often include jaundice, pruritus, and failure to thrive.
Clinical assessment: Diagnosis of PFIC has traditionally been made through clinical assessments (including symptoms, family history, laboratory investigation, liver ultrasound and liver biopsy).

treatment

Medical Treatment

Dietary supplements: Fat-soluble vitamins, lipids, and caloric supplements are first-line treatment choices for patients with all types of PFIC to prevent the side effects of chronic cholestasis.
Ursodeoxycholic acid (UDCA): UDCAs are the most commonly used off-label medication for people living with PFIC to improve bile flow and reduce symptoms. While it is generally well tolerated and has few side effects, its benefits are often limited. Some individuals may see early improvement in symptoms, but these effects are not always lasting.
Rifampicin: Rifampicin is another commonly prescribed, off-label, antipruritic drug, often used in combination with UDCA, which has demonstrated little success in terms of sustained symptomatic responses.
Ileal bile acid transporter (IBAT) inhibitors: IBAT inhibitors are medications that provide a non-surgical way to interrupt the normal recycling of bile acids in the body (enterohepatic circulation).
- Maralixibat (IBAT) is a medication that targets bile acid transport in the intestine (IBAT). It is approved to treat cholestatic pruritus (itching) in adults and children with PFIC who are 12 months of age and older. However, it is not recommended for a subgroup of people with PFIC type 2 who have certain changes in the ABCB11 gene that result in little or no function of the bile salt export pump (BSEP) protein. Maralixibat is available as both a tablet and an oral solution.
- Odevixibat (IBAT) is the first oral treatment approved for pruritus in people with PFIC aged 3 months and older. Similar to maralixibat, it is not recommended for some individuals with PFIC type 2 who have specific ABCB11 gene changes. Odevixibat comes in capsule form as well as pellets that can be taken by mouth.

Surgical Treatment

Biliary diversion: Biliary diversion is a surgical procedure that reduces the buildup of bile acids by interrupting their circulation between the liver and intestines. This can help relieve severe itching. The procedure may be done using external drainage, which involves creating a small opening (stoma) on the abdomen, or internal drainage, which creates a new pathway between the gallbladder and the intestine. Many people experience improvement in itching and a slower progression of disease, although not everyone responds. Possible complications can include infection, issues with the stoma, rectal bleeding, or diarrhea.
Ileal bypass procedures: A procedure that reroutes the last part of the small intestine, where most bile acids are normally reabsorbed. It may be considered for some individuals, including those who have had their gallbladder removed. However, long-term benefits are uncertain, and symptoms may return over time.
Liver transplantation: Liver transplantation is often the most effective treatment for people with PFIC, particularly in advanced stages of liver disease. It can greatly improve quality of life and long-term outcomes. Similar to any major surgery, there are risks to be mindful of, including organ rejection, possible disease recurrence in some cases, and side effects from lifelong medications used to prevent rejection.

Nutritional Management

Supplemental fats and vitamins as nutritional therapy for PFIC. These can include:

Infant and pediatric formulas that are rich in medium-chain triglycerides, a type of fat that people with PFIC generally can absorb.
Liquid vitamin supplements to prevent against deficiencies.

Lifestyle Management

Warm temperatures, whether from air or water, may make itching feel worse. To help prevent overheating, bathe children in lukewarm water rather than hot water. During warmer weather, try to keep cool by using air conditioning, taking cool showers or baths, or applying cold compresses to the skin.
Keeping the skin well hydrated is also important. When the skin’s protective barrier is weakened, it becomes easier for irritants to reach nerve endings and immune cells, which can increase itching. Regular use of emollients, such as creams and ointments, can help restore this barrier and lock in moisture.

additional resources

Here are a few questions to ask your doctor or medical team:

What is the status of my liver?
What treatments are available to manage my symptoms?
What lifestyle changes should I make to improve my liver condition?
Is my child at risk of having progressive familial intrahepatic cholestasis?