Progressive familial intrahepatic cholestasis (PFIC)

Quick summary - PFIC

• Progressive familial intrahepatic cholestasis (PFIC) is the name given to a group of conditions in which a digestive fluid, called bile, is not released properly from the liver.
• PFIC is rare and affects around 1 in 50,000 to 1 in 100,000 people.
• PFIC is a genetic condition. This means it is caused by changes (mutations) in a person’s genes.
• PFIC is usually diagnosed in infants and toddlers, but a diagnosis can take time.
• Blood tests, scans and biopsies may be used to help with diagnosis.
• There are different types of PFIC with different levels of severity.
• The main symptoms of PFIC are itching (pruritus) and yellowing of the whites of the eyes and skin (jaundice).
• Currently there is no cure for PFIC. However, dietary support, medicines and surgery can reduce the symptoms and complications.
• Many children with PFIC will need a liver transplant at some point in their life.
• Support services for children and young people with PFIC and their families are available from Children’s Liver Disease Foundation.

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What is progressive familial intrahepatic cholestasis?

Progressive familial intrahepatic cholestasis (PFIC) is the name given to a group of conditions in which a digestive fluid, called bile, is not released properly from the liver into the gut (gastrointestinal tract).

When the flow of bile reduces or stops, it builds up inside the liver. This is called cholestasis.

Cholestasis can damage the liver. The liver cells can start to die and are replaced with scar tissue (fibrosis). This may eventually lead to severe scarring of the liver, known as cirrhosis.

PFIC is a rare condition which affects around 1 in 50,000 to 1 in 100,000 people. It affects both males and females.

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What is bile and why is it important?

Bile is a green/yellow liquid made by the liver. The colour is due to bilirubin, a natural waste product made when old red blood cells break down in the spleen.

Bile is made up of:

• bile acids (which help to digest fat)
• bilirubin (a natural waste product)
• cholesterol (a type of fat made in the liver)
• other fats
• water
• other waste products

Bile is made by the liver and stored in the gallbladder. When you eat food, the gallbladder releases bile through the bile ducts. It moves into a part of the small intestine called the duodenum. The bile helps your body break down food and remove waste products.

Bile has several important jobs:

• It helps the body digest food by breaking down fats
• It helps the body absorb vitamins A, D, E & K
• It helps the body get rid of waste products such as bilirubin and leftover cholesterol. Both pass out in the poo (stool).

PFIC happens when there are problems in the system which makes and releases bile. Retention of bile in the liver or bile ducts causes waste products to remain in the body. This damages liver cells.

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What causes PFIC?

PFIC is a genetic condition. This means it is caused by changes (mutations) in a person’s genes.

Genes are sections of DNA that contain the instructions for making proteins. These proteins are the building blocks for everything in the body. They control how it grows and works.

Many of us will have some changes in our genes. Usually, these do not have any impact. Sometimes, however, these changes can cause diseases and other problems.

There are different types of PFIC. Each type is caused by changes in a different gene.

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What are the chances of a child inheriting PFIC from their parents?

PFIC usually only happens when both parents are carriers of the change (mutation) that causes PFIC.

A carrier of the condition has one copy of the mutated gene. They do not have the disease themselves and will probably not know they are at risk of passing on the mutated gene. This is why conditions like PFIC can come ‘out of the blue’ for families. It is only when a child receives two mutated genes (one from each parent) that they develop the disease.

If both parents are carriers, the chance of a child receiving a mutated gene from both parents (and therefore having PFIC) is one in four (25%). If the child only receives one copy of the mutated gene, they won’t have PFIC, but will be a carrier. This pattern is called “autosomal recessive”.

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How is PFIC diagnosed?

PFIC is usually diagnosed in infants and toddlers. It can take time for a PFIC diagnosis to be made because the condition is rare and your child may need different tests.

Tests used to help diagnose PFIC:

The first year after diagnosis was about finding our “new normal”. We adapted and realised our daughter was still our beautiful baby girl. She taught us so much about what is important in life.
– Parent

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What are the different types of PFIC?

here are three main types of PFIC:

• F1C1 deficiency (previously known as PFIC1)
• BSEP deficiency (previously known as PFIC2)
• MDR3 deficiency (previously known as PFIC3)

Other types of PFIC are also being discovered as we learn more about the gene mutations.

Each type of PFIC is caused by a change (mutation) in a different gene. These changes can be more or less severe in different children. This leads to differences in the disease, its severity, symptoms and the treatments available.

Other types of PFIC

Doctors have identified other types of PFIC, but they are very rare:

• TJP2 deficiency
• FXR deficiency
• MY05B deficiency
• USP53 deficiency
• FXR deficiency

Researchers think they will be able to identify more genetic causes of PFIC as testing gets better.

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What are the symptoms of PFIC?

Symptoms in children with PFIC often begin in infancy or early childhood. The severity of symptoms will vary from child to child and will depend on the type of PFIC they have.

I used to be jaundiced some days and I even came up with a yellow superhero called Banana Girl to describe myself!
– Child

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What are the possible complications of PFIC?

In children with PFIC, there are some possible complications. Bile trapped in the liver may cause damage that gets worse over time. This can cause the liver to become stiff and scarred (fibrosis). It may also lead to severe scarring, known as cirrhosis.

The effects of severe scarring (cirrhosis) of the liver include:

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How is PFIC treated

There is no cure for PFIC. However, dietary support and medicines can help reduce the symptoms and complications. Surgery may also be an option in a small number of cases.

The medical team will recommend treatments. These may differ from child to child depending on the severity of the symptoms.

Dietary support

Children who have liver disease are likely to need extra calories and nutrition. Eating and drinking normally doesn’t always provide this. Extra support for your child may include:

• MCT (medium chain triglyceride) formulas and diets

MCT is a type of fat. It is more easily absorbed and is a good source of energy. Your child’s dietitian will prescribe special milk formulas and supplements containing MCT. They will also provide a list of suitable foods for older children.

• Fat soluble vitamins (vitamins A, D, E and K)

These vitamins are usually given by mouth (orally). In some cases, they have to be given by injection.

• Nasogastric feeding

Nasogastric feeding may be used if your child needs more calories or is not growing well. This involves passing a very thin, soft tube up the nose, down the back of the throat and into the stomach. A special milk formula will be given overnight using a pump. Parents/carers can be taught how to do this at home.

Find more information in CLDF’s leaflet: Nutrition.

I was petrified of needing an NG tube for feeding but was really well supported when that day came. It gave her the energy to enjoy things again.
– Parent

I remember the itch felt like it was under the skin. Having to scratch myself felt like a reflex and I just couldn’t ignore it. It was worse at night because I had nothing to distract me.

– Child

Medicines

The choice of medication for children with PFIC will depend on the PFIC type and the severity. The main purpose of the medicines is to reduce symptoms. In particular, doctors try to reduce the severe itching (pruritus). Medicines are also used to try and help slow down the disease.

• Ileal bile acid transporter (IBAT) inhibitors

This type of drug works by blocking a protein called the ileal bile acid transporter (IBAT). This protein is present in the intestines and transports bile acids back into the liver. By blocking the protein, the drug reduces the amount of bile acids that build up in the liver. Clinical trials show that this may help limit liver damage and reduce pruritus (itching).

• Cholestyramine

This drug mixes with bile acids in the small intestine. It then stops them being reabsorbed into the blood stream. In some cases, it may help to reduce itching (pruritus), but the results vary. It will not be given at the same time as vitamin supplements as it can stop them being absorbed properly.

• Ursodeoxycholic acid

This is a bile salt that occurs naturally in small amounts in bile. Taking it as a medicine can help improve bile flow out of the liver. This can reduce jaundice and/or itching (pruritus) and can help improve liver function. It has been found to be particularly useful in MDR3 deficiency.

• Rifampicin

This is an antibiotic used to treat various conditions. It is not licensed to treat itch (pruritus) but is often used by liver doctors to help with this symptom. It is used very carefully in severe liver disease because it can cause a rise in liver function tests. Rifampicin is a red colour and it can make wee (urine), spit (saliva) and tears turn orange/red. This side-effect is harmless.

Other medicines which have been used to treat itch (pruritus) in some children include:

• Phenobarbital
• Naltrexone
• Ondansetron

Some medicines in PFIC are used “off-label”. This means they were developed for other diseases, but sometimes work in PFIC. The response to off-label medicines can vary. There is currently no strong evidence to show that they are effective in children with PFIC.

I used to love some of my medications when I was little. I used to give it to myself from when I was a baby. I actually miss the taste of some of them now!
– Child

Potential operations

Not all children and young people respond well to dietary support and medicines. Sometimes they do not give enough relief from itching (pruritus). In a small number of children, the medical team may consider surgery. They will carefully assess your child’s condition before recommending any of these operations. Not all operations will be suitable for all children.

• Partial external biliary diversion (PEBD)

This is only suitable for children who do not have advanced liver disease. During the operation, the surgeon opens the end of the gallbladder. They bring it out through the skin to form an opening known as a stoma. This sits on the surface of the tummy (abdomen). Your child would need to wear a bag over the stoma to collect bile. In some cases, the surgeon uses a short section of small intestine to connect the gallbladder to the surface of the tummy (abdomen).

• Partial internal biliary diversion (PIBD)

During this operation the surgeon connects the gallbladder to the large intestine. This is done using a piece of small intestine. There is no need for a bag on the outside of the body.

• Ileal exclusion (IE)

During this operation the surgeon creates a bypass around a part of the bowel called the distal ileum. The aim is to reduce the amount of bile salts re-entering the bloodstream. There is no need for a bag on the outside of the body.

Liver transplant

Many children with PFIC will need a liver transplant at some point in their life. This may be during childhood or when they are an adult. This is because the treatments available may only give some relief from symptoms. They are not a cure and can only slow down liver disease.

A liver transplant is an operation to remove a liver that does not work. It is replaced with a healthy liver from another person (donor). Children with PFIC may receive a whole, split or reduced liver from a deceased donor. It is also possible that they may receive part of a liver from a living donor.

A successful liver transplant will help a child survive when the liver is failing. It will also significantly improve a child’s quality of life. It is currently the only definitive treatment for PFIC.

It is important to remember that a liver transplant is a major operation. It will only be done after the benefits and risks have been carefully weighed up. Following a successful liver transplant children will need lifelong medication and follow up.

Find more information in CLDF’s leaflet: Liver Transplantation.

The year before transplant was tough but we never felt alone and the incredible medical team around our child literally carried us through.
– Parent

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Special thanks

Information reviewed: March 2024

Next review date: March 2027

We would like to thank staff at each of the specialist paediatric liver centres: Birmingham Children’s Hospital, King’s College Hospital and Leeds Children’s Hospital. We would also like to thank the families who helped us produce this information.

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