Primary biliary cholangitis (PBC) is a condition that slowly damages the bile ducts in the liver. Bile is a liquid produced in the liver to aid digestion. The bile ducts are the tubes which carry the bile from the liver to the gallbladder where it is stored ready for use when you eat.
If the bile ducts become blocked then, in time, the flow of bile is restricted and bile builds up in the liver. This damages liver cells which in some cases leads to scarring of the liver (cirrhosis). Common early symptoms are itch and tiredness. Other symptoms develop as the disease progresses. Medicines which aim to ease symptoms and slow the progression of the disease may be used. A liver transplant may be needed if the liver becomes badly damaged.
What are bile and bile ducts?
Bile is a yellow-green liquid that contains various chemicals and bile salts. Bile helps you to digest food, particularly fatty foods. It also helps the body to absorb certain vitamins (A, D, E and K) from the food that you eat.
Bile is made by liver cells. Liver cells pass out bile into a network of tiny tubes called bile ducts. They join together (like tributaries of a river) to form the larger common bile duct. Bile constantly drips down the tiny bile ducts, into the common bile duct, and into the first part of the small intestine (which is called the duodenum).
The gallbladder lies under the liver. It is like a pouch off the common bile duct and fills with bile. It is like a reservoir that stores bile. The gallbladder squeezes (contracts) when we eat, as the bile is needed to aid digestion. This empties the stored bile back into the common bile duct and out into the duodenum.
What does the liver do?
The liver is in the upper right part of the tummy (abdomen). Its functions include:
- Storing glycogen (fuel for the body) which is a starch made from sugars. It acts as 'quick access' energy for the body. When required, glycogen can be quickly broken down into glucose which is released into the bloodstream.
- Helping to process fats and proteins from digested food.
- Making proteins that are essential for blood to clot (clotting factors).
- Processing many medicines which you may take.
- Helping to remove or process alcohol, poisons and toxins from the body.
- Making bile which passes from the liver to the gut and helps to digest fats.
What is primary biliary cholangitis (PBC)?
PBC is a condition that affects the bile ducts and that gradually closes them off. It is called:
- Primary - because the cause is not known. (That is, it is not secondary to any known cause such as alcohol or poisons.)
- Biliary - because it affects the bile ducts.
- Cholangitis - because there is inflammation of the bile ducts.
In PBC, inflammation develops around the small bile ducts within the liver. The inflammation can slowly damage the bile ducts. The bile ducts gradually become blocked due to the inflammation. Bile is not able to flow down any ducts that become blocked.
This process tends to get worse very slowly, and the number of damaged and blocked bile ducts gradually increases. If bile cannot flow down bile ducts, the bile builds up in the liver cells. In time, the liver cells also become damaged by the accumulation of bile, and the substances in bile may also spill over into the bloodstream.
As damage to the liver cells becomes worse, cirrhosis may gradually develop in the liver. The scarred liver is unable to function properly. In time, cirrhosis can cause liver failure and other serious problems.
In the early stages of the disease, the main problem caused by PBC is the build-up of substances in the liver and bloodstream. Normally, these substances would be drained into the first part of the intestine (the duodenum) as part of bile. Cirrhosis occurs only in the later stages of the disease. The rate of decline from early stages of the disease to the later, more serious, stages of the disease can vary from person to person.
Not all people with PBC develop cirrhosis. Moreover, if cirrhosis does occur, it typically develops several years after the disease first begins (that is, after several years of inflammation of the bile ducts).
What causes primary biliary cholangitis (PBC)?
The exact cause is not known. It is thought that PBC is an autoimmune disease. The immune system normally defends us by attacking bacteria, viruses, and other germs with antibodies, white blood cells, and other defence mechanisms. In people with autoimmune diseases, the immune system turns against and attacks tissues of the body. It is not clear why this happens. Some people seem to have a tendency to develop autoimmune diseases. Their immune systems are more readily triggered into attacking parts of their own body. In such people, something may trigger the immune system to attack the body's own tissues. The exact trigger is not known. Possible triggers that have been suggested are some kind of infection or some kind of poison (toxin). There may also be a genetic tendency to develop PBC, as it seems to run in some families.
In people with PBC, the immune system attacks the cells that line the small bile ducts in the liver. This causes inflammation and damage in and around these bile ducts. Gradually they become scarred and may block off.
People with PBC have an increased chance of developing other autoimmune diseases. For example, Sjögren's syndrome, two thyroid diseases called Graves' disease and Hashimoto's thyroiditis, Raynaud's phenomenon and scleroderma.
Who gets primary biliary cholangitis (PBC)?
PBC is an uncommon condition. It affects about 1 in 5,000 people in the UK. About 9 in 10 cases occur in women. It most commonly develops in women aged between 30 and 65.
What are the symptoms of primary biliary cholangitis (PBC)?
The most common early symptoms include the following:
- Tiredness (fatigue). This is often the earliest symptom. It can be quite a disabling type of tiredness. The reason PBC causes tiredness is not clear. However, this is not a specific symptom, as tiredness can have many causes.
- Itch (pruritus). This is a common symptom, but does not always occur. It is sometimes severe and distressing with the whole skin feeling itchy. The cause of the itch is not always clear. It may be due to a chemical from the bile, which builds up in the bloodstream.
- Discomfort over the liver - upper right of the tummy (abdomen). This occurs in about 1 in 5 cases.
- Red or pink blotchiness of the hands may develop.
- Some people develop a feeling of sickness (nausea), bloating or diarrhoea. Stools (faeces) may be pale, bulky and difficult to flush away (called steatorrhoea or fatty stools) because of the your body's difficulty with digesting fat when you have PBC.
- Some patients find they develop a distaste for alcohol. Patients who smoke may find they 'go off' smoking.
When a doctor examines you, he or she may be able to feel that your liver is enlarged. As the disease progresses, yellowing of the skin and the whites of the eyes (jaundice) develops. This is due to a build-up of a chemical in bile (bilirubin) in the bloodstream. If scarring of the liver (cirrhosis) develops, other liver-related symptoms are likely to develop.
Some people with PBC have no symptoms
PBC is sometimes diagnosed by chance when blood tests done for other reasons show abnormalities which are due to PBC. Some of these people never develop symptoms. However, many will develop symptoms at some point as the disease progresses.
Symptoms of related disorders
As mentioned, some people with PBC also have other autoimmune diseases. Therefore, symptoms related to these other diseases also occur in some cases. For example, a dry mouth and dry eyes are the main symptoms of Sjögren's syndrome.
Symptoms from complications
The risk of developing 'thinning' of the bones (osteoporosis) is increased in women with PBC. (See separate leaflet called Osteoporosis for more details.) Other complications related to the disordered function of the liver can develop in some cases. For example, problems with the kidneys and pancreas can occur. Liver cancer is a very uncommon complication.
How is primary biliary cholangitis (PBC) diagnosed?
If PBC is suspected from your symptoms, a blood test will usually confirm the diagnosis. Most people with PBC have:
- A high level of certain liver chemicals (enzymes) in the bloodstream. (See separate leaflet called Liver Function Tests for more details.)
- An antibody called antimitochondrial antibody. This antibody could possibly have something to do with causing the disease, as it attacks part of cells called mitochondria.
Many people with PBC also have a raised cholesterol level. However, this is usually mainly the good cholesterol which is called high-density lipoprotein (HDL) cholesterol. This means that despite having higher cholesterol, there is no increased risk of heart disease. (See separate leaflet called Cholesterol for more information.)
Your doctor may arrange for you to have an ultrasound scan of your liver. Gel is applied to the skin of your tummy (abdomen). The ultrasound probe is moved across your skin (similar to the scan that women have during pregnancy). This allows the doctor to look at your bile ducts for signs of scarring and blockage. The doctor can also check for any other possible causes of your symptoms.
A liver biopsy involves taking a small sample of tissue from a part of the liver. This involves a local anaesthetic and the passage of a hollow needle between two lower ribs on the right-hand side. This enables a tiny piece of liver tissue to be taken. The sample is then examined under the microscope to look for abnormal cells. If PBC is present then there are typical changes seen under the microscope. The biopsy can also give an indication of how severe the condition is. For example, whether liver scarring (cirrhosis) has developed, and if so, how badly. (See separate leaflet called Liver Biopsy for more details.)
What is the treatment for primary biliary cholangitis (PBC)?
There is no cure for PBC. Treatments aim to ease symptoms and to slow the progression of the disease. In cases where the liver progresses to severe scarring (cirrhosis) and liver failure, liver transplant can be life-saving.
Treatment to ease symptoms
Itch (pruritus) can be a distressing symptom and can be difficult to treat. Antihistamines may be used initially to help to relieve itch. However, colestyramine (trade name Questran®) is the most commonly used medicine for itch.
This medicine works by binding to bile in the gut to stop it from making its way back to the liver. When bile gets into the gut, it travels down to the large intestine. Here, some of it is taken (absorbed) back into the bloodstream, and returns to the liver to be reused. As colestyramine binds to bile in the the large intestine, it stops this reabsorption and so more bile than usual is passed out with the stools (faeces). This helps to reduce the build-up of bile in the liver and bloodstream, which often eases itch. There may be a delay of 1-4 days after starting treatment before itch improves. Other bile-binding medicines are sometimes used.
Other medicines are sometimes used to ease itch if the above are not helpful. For example, rifampicin. It is not clear how these work, but they do help in some people. Ursodeoxycholic acid (UDCA, or urso) - see below - may also relieve itch. Plasmapheresis, which is like a plasma exchange, has been used in some cases of persistent, severe itch. This may need to be repeated.
Dry skin can make itch worse, so using liberal amounts of moisturiser is useful if you have dry skin. It can help to keep the moisturiser cool.
No medicines seem to ease tiredness (fatigue) which is often a main symptom.
Treatment to slow the progression of the disease
There is no medicine that stops or reverses the disease. However, some medicines may slow down the progression of the disease in some people. UDCA is the most common medicine used. It is used with the aim of slowing the progression of the disease. It works by changing the 'makeup' of bile in the liver. This may reduce the harmful effect of bile on the liver cells. However, its effectiveness is disputed and it may not work in everyone. Some studies have shown that it seems to work best in the early stages of PBC. Some evidence suggests that UDCA may help to delay the need for a liver transplant in some people with PBC. It may prolong the time for which they feel well, and may therefore help to keep them alive for longer. However, its effect in the later stages of PBC (in people who have developed scarring of the liver (cirrhosis)) does not seem to be as good. It may help to ease itch.
Immunosuppressive medicines are sometimes used. For example, penicillamine, azathioprine, methotrexate, ciclosporin and steroids. These work by suppressing the immune system. Unfortunately, again, there is little clear-cut evidence to say how effective these medicines are in treating PBC. They also all have a risk of causing significant side-effects.
There is a lot of interest in a new group of medicines called biologics, which look promising as treatments for autoimmune diseases. Research continues in this area so there may be further developments in the treatment of PBC in the next few years.
Your specialist will advise on the pros and cons of trying any particular medicine.
Treatment of associated diseases
As mentioned, various other autoimmune diseases are more common in people with PBC. This means that you may need treatment for these too.
'Thinning' of the bones (osteoporosis) is more common in women with PBC. The prevention and treatment of osteoporosis is the same as for any other woman and is discussed in the separate leaflet called Osteoporosis.
Treatment of cirrhosis and liver failure
See separate leaflet called Cirrhosis for more details about cirrhosis. A liver transplant is an option if the liver becomes badly damaged due to cirrhosis. This is a major operation and is not to be undertaken lightly. However, it can be a life-saving measure and the results are often very good. Some people with severe itch which has not responded to any other treatment have a liver transplant even if their liver is not too badly damaged. This is because severe itch is an extremely distressing symptom which can severely reduce their quality of life.
Sometimes, PBC can come back and affect the transplanted liver. However, this does not necessarily happen and, if it does, can take up to 15 years before it returns.
Do I need to take any other precautions?
If you have PBC, you may find that you are no longer able to cope with drinking alcohol. Some people just drink a small amount of alcohol on special occasions. The amount of alcohol that is sensible for you to drink will vary from person to person and will depend on the degree of damage to your liver. You should ask your doctor to advise about whether you can drink alcohol and how much alcohol is sensible for you.
You should always remember to tell a doctor or a pharmacist that you have PBC before you start taking any medication. (This includes any medicines, supplements or remedies that you may buy over the counter.) This is because a lot of medicines are processed in the liver. Because your liver may not be working so well if you have PBC, you may have some unwanted effects from certain medicines.
What is the outlook (prognosis)?
PBC is a progressive disease. However, in many cases, the disease progresses very slowly over a number of years. Many people have very few problems for as long as several decades. At the start of the disease it is difficult to predict if, or when, the disease will progress to scarring of the liver (cirrhosis) and liver failure.
Coping with the common symptoms of itch (pruritus) and tiredness (fatigue) can be difficult. Research continues to try to identify medicines that may be more effective at preventing the progression of the disease than those currently available.
Dr Tim Kenny
Dr Mary Lowth
Prof Cathy Jackson