Primary Biliary Cirrhosis

What does the liver do?

The liver is in the upper right part of the abdomen. It has many functions which include:

• Storing glycogen (fuel for the body) which is made from sugars. When required, glycogen is 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 are bile and bile ducts?

Bile is a yellow liquid that contains various chemicals and bile salts. Bile helps to digest food, particularly fatty foods.

Bile is made by cells in the liver. Liver cells pass out the bile into tiny tubes called bile ducts. There is a network of bile ducts throughout the liver. They join together (like the branches of a tree) to form the larger 'common bile duct'. Bile constantly drips down the tiny bile ducts, into the common bile duct, and into the duodenum (part of the gut - the first part of the small intestine).

The gallbladder lies under the liver. It is like a pouch that comes off the common bile duct, and fills with bile. It is like a reservoir that stores bile. The gallbladder squeezes when we eat. This empties the stored bile back into the common bile duct, and out into the duodenum.

What is primary biliary cirrhosis?

PBC is a condition that affects the bile ducts. It is called:

• Primary - because the cause is not known. (That is, it is not 'secondary' to any known cause such as alcohol or poison.)
• Biliary - because it affects the bile ducts.
• Cirrhosis - because as the disease progresses it can damage the liver cells and cause scarring of the liver. Cirrhosis means scarring of the liver and has various causes. PBC is an uncommon cause of cirrhosis.

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 and damage. 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. Bile may also spill into the bloodstream.

As damage to the liver cells becomes worse, scarring (cirrhosis) may gradually develop in the liver. In time, cirrhosis can cause liver failure and other serious problems. (There is a separate leaflet called 'Cirrhosis' which describes cirrhosis in more detail.)

In the early stages of the disease, the main problem is the build up of substances in the liver and bloodstream that are normally drained into 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 case to case.

In fact, the term PBC is controversial because not all people with PBC develop cirrhosis. Also, if cirrhosis does occur, it typically develops several years after the disease first begins (after several years of inflammation of the bile ducts).

What causes PBC?

The exact cause is not known. It is thought that PBC is an autoimmune disease. The immune system normally attacks bacteria, viruses, and other 'germs' with antibodies, white blood cells, etc. In people with autoimmune diseases, the immune system attacks tissues of the body. It is not clear why this happens. Some people seem to have a tendency to develop autoimmune diseases. In such people, something might trigger the immune system to attack the body's own tissues. The trigger is not known.

In people with PBC, the immune system attacks cells that line the small bile ducts in the liver. This causes inflammation and damage in and around the bile ducts in the liver.

People with PBC have an increased chance of developing other autoimmune diseases. For example, Sjogren's Syndrome, thyroid disease, Raynaud's Phenomenon, scleroderma.

Who gets PBC?

PBC is an uncommon condition. It affects about 1 in 1000 people in the UK. About 9 in 10 cases occur in women. It most commonly develops in women aged between 30 and 60.

What are the symptoms of PBC?

The most common early symptoms:

• Tiredness (fatigue) is often the first symptom to develop. It can be quite a disabling type of tiredness. The reason PBC causes tiredness is not clear.
• Itch 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 clear. It may be due to a chemical from the bile which builds up in the bloodstream.
• Discomfort over the liver (upper right of abdomen) occurs in about one in five cases.
• Red or pink blotchiness of the hands may develop.

When a doctor examines you, he or she may feel that your liver is enlarged. As the disease progresses jaundice (yellowing of the skin) develops. This is due to a build-up of bilirubin (a chemical in bile) which builds up in the bloodstream.

If cirrhosis develops, other liver-related symptoms are likely to develop. (See separate leaflet called 'Cirrhosis'.)

Some people with PBC have no symptoms
PBC is sometimes diagnosed by chance when blood tests that are done for other reasons show abnormalities which are due to PBC. Some of these people never develop symptoms. However, many of these people 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 Sjogren's syndrome.

Symptoms from complications
The risk of developing osteoporosis is increased in women with PBC. (See separate leaflet called 'Osteoporosis'.) Other complications related to disordered function of the liver develop in some cases. For example, problems with the kidneys and pancreas. Liver cancer is an uncommon complication.

How is PBC diagnosed?

Blood tests
If PBC is suspected from the symptoms, a blood test will usually confirm the diagnosis. Most people with PBC have:

• A high level of certain liver enzymes (chemicals) in the bloodstream. (See separate leaflet called Liver Function Tests'), and...
• An antibody called antimitochondrial antibody. This antibody may have something to do with causing the disease as it 'attacks' part of cells called mitochondria.

Liver biopsy
A liver biopsy is when a small sample of tissue is removed from a part of the liver. The sample is then examined under the microscope to look for abnormal cells. Typical changes seen under the microscope from the biopsy sample can confirm the diagnosis of PBC. The biopsy can also give an indication of the severity. For example, if cirrhosis is present, and if so, how badly. (See separate leaflet called 'Liver Biopsy'.)

What is the treatment for PBC?

There is no cure for PBC. Treatments aim to ease symptoms and to slow the progression of the disease. A liver transplant can be life-saving in the later stages of the disease.

Treatments to ease symptoms
Itch can be a distressing symptom and can be difficult to treat.

Cholestyramine (trade name Questran) is the most commonly used medicine for itch. It works by 'binding' to bile in the gut. (When bile gets into the gut, it travels down to the large intestine where some of it is absorbed back into the bloodstream, and goes back to the liver to be reused. As cholestyramine binds to bile in the the large intestine, it stops this 'reabsorption' and so more bile than usual is passed out with the faeces (stools). This helps to reduce a 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, rifampacin, naloxone or phenobarbitone. It is not clear how these work, but they do in some cases. UDCA (see below) may also relieve itch. Plasmapheresis (like a plasma exchange) has been used in some severe cases of persistent, severe itch.

Dry skin can make itch worse, so using liberal amounts of moisturiser is useful if you have dry skin.

No medicines seem to ease tiredness which is often a main symptom.

Treatments 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 cases.

Ursodeoxycholic acid (UDCA) is the most common medicine used with the aim of slowing the progression of the disease. However, research trials indicate that, at best, it only has a modest effect of slowing the disease in some people, and may not help at all in others. However, it may ease itch. It works by changing the make-up of bile in the liver which may reduce the harmful effect of bile on the liver cells.

Immunosuppressive medicines are sometimes used. For example, penicillamine, azathioprine, methotrexate, cyclosporin, and steroids. These work by suppressing the immune system. But again, there is little clear cut evidence to say how effective they are in treating PBC. They all have a risk of causing significant side-effects.

Your specialist will advise on the pros and cons of trying any particular medicine.

Treatments of associated diseases
As mentioned, various other autoimmune diseases are more common in people with PBC. So, you may need treatment for these too.

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 a separate leaflet called Osteoporosis.

Treatment of cirrhosis and liver failure
See separate leaflet called Cirrhosis for details of cirrhosis.

A liver transplant is an option if the liver becomes badly damaged and fails. This is a major operation and not to be undertaken lightly. However, it can 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.

What is the outlook (prognosis)?

PBC is a progressive disease. However, in many cases, the disease progresses very slowly over a number of years. At the outset of the disease it is difficult to predict if, and when, the disease will progress to cirrhosis and liver failure. Coping with the common symptoms of itch and tiredness can be difficult. Research continues to identify medicines that will be more effective at preventing the progression of the disease than those currently available.

Further information and advice

Primary Biliary Cirrhosis Foundation
54 Queen Street, Edinburgh, EH2 3NS
Tel: 0131 225 8586    Web: www.pbcfoundation.org.uk
A charity established to provide help, support and information for sufferers of PBC, their families and friends.

British Liver Trust
2 Southampton Road Ringwood BH24 1HY
Tel: 0870 770 8028   Web: www.britishlivertrust.org.uk
A national organisation devoted to the prevention, treatment and cure of all liver diseases. Has an extensive range of publications on individual liver conditions

© EMIS and PIP 2005   Updated: October 2006