The exact cause of primary biliary cirrhosis (PBC) is unknown, although it is thought a combination of genetic and environmental factors may play a part.

These are described below.

• genetic factors – the genes that you inherit make you susceptible to developing PBC
• environmental factors – something in the environment triggers PBC (see possible triggers, below)

Autoimmune condition

Most experts believe that PBC is an autoimmune condition. In these types of conditions, something goes wrong with the immune system (the body’s natural defence against infection and illness). Instead of fighting off infection, the immune system attacks healthy tissue. It is not known what causes the immune system to malfunction and attack the bile ducts.

In cases of PBC, the immune system sends specialised cells, known as T-cells, to the site of the bile ducts. T-cells usually kill bacteria and viruses.

The T-cells start to damage the surface of the bile ducts, which gradually become extensively scarred and disrupt the usual flow of bile. As the amount of bile in the liver increases, further scarring of the liver (cirrhosis) occurs.

Over time, high levels of cirrhosis cause the liver to lose some, and eventually all, of its function. As the liver plays a vital role in filtering out impurities from your blood, a loss of liver function is potentially fatal.

Other autoimmune conditions

Having one autoimmune condition such as PBC can make it more likely you will have other autoimmune conditions. For example, people with PBC may also have:

• autoimmune thyroid disease – a condition that affects the thyroid gland in your neck, which produces hormones
• an underactive thyroid (hypothyroidism) – a type of thyroid condition where the thyroid gland does not produce enough hormones; around a fifth of people with PBC also have an underactive thyroid gland, which may be responsible for the fatigue
• rheumatoid arthritis – a condition that causes pain and swelling in the joints 
• scleroderma – a condition that affects the connective tissue (the supporting tissues of the body), causing hard, puffy and itchy skin
• autoimmune hepatitis – a very rare cause of chronic (long-term) hepatitis, where the white blood cells attack the liver
• Sjogren’s syndrome – a disorder where the white blood cells attack the body’s tear and saliva glands
• Raynaud’s phenomenon – a common condition of the blood vessels that supply blood to the skin, causing them to narrow and reduce blood flow to the hands
• coeliac disease – a common digestive condition where a person is intolerant (has an adverse reaction) to the protein gluten

Increased risk

There is some evidence to suggest that certain things increase your chances of developing PBC. These risk factors are explained below.

Gender

PBC occurs mostly in women. Less than one in 10 cases of PBC occur in men.

One theory for this is that the immune system is upset by the female sex hormone, oestrogen.

Family history

Having a close relative with PBC means you are more likely to develop the condition yourself. For example, if you are female and your mother has or has had PBC, you are much more likely to develop PBC than someone who has no relatives with the condition. However, the risk is still low. More than 99% of people who have a first-degree relative with PBC will not develop the condition themselves.

This family connection has led researchers to speculate that certain genes (units of genetic material) inherited from your parents may make you more likely to develop PBC. 

Possible triggers

Certain things may trigger PBC in people with a genetic tendency. These include:

• infections, such as a urinary tract infection (UTI)
• hormone replacement therapy (HRT) – a treatment used to replace the female hormones that a woman’s body no longer produces because of the menopause
• using nail varnish or cosmetics 
• smoking cigarettes or having a past history of heavy smoking
• living near to where toxic waste has been dumped

However, none of these have been proven as definite triggers of PBC. Most people who are exposed to them will not develop the condition. At present, there is nothing to suggest you should reduce your exposure to these triggers to lower your risk of developing PBC.

If primary biliary cirrhosis (PBC) is not treated, it can lead to complications such as an increased chance of osteoporosis or liver cancer.

Osteoporosis

Damage to your liver caused by primary biliary cirrhosis (PBC) can affect its ability to absorb vitamin D and calcium, both of which are needed to keep bones strong and healthy. This could lead to your bones becoming weak and brittle, a condition known as osteoporosis.

Osteoporosis affects around one-third of people with primary biliary cirrhosis (PBC). Compared with someone of the same age and sex, a person with PBC is more than four times more likely to develop osteoporosis than someone who does not have PBC. 

A dual energy X-ray scan, usually referred to as a DEXA scan, is a type of X-ray that measures the amount of calcium in your bones. This measurement is often referred to as bone mineral density (BMD). Your BMD may be tested every two to four years to see if you are at risk of developing osteoporosis.

If you are, your GP may prescribe vitamin D and calcium supplements to help maintain your bone strength. In some cases, you may also need more specific treatment, such as bisphosphonates. This is a medicine that slows the rate at which the cells break down bone (osteoclasts). This maintains bone density and reduces the risk of fracture.

Read more information about how osteoporosis is treated.

Exercise

Osteoporosis can be prevented with regular exercise, particularly weight-bearing exercises (where your feet and legs support your weight). For example:

• running
• dancing
• aerobics

Read more information about preventing osteoporosis.

Liver cancer

If you have PBC, the progressive damage to your liver slightly increases your risk of developing liver cancer. Due to this slightly increased risk, you may be referred for regular check-ups for liver cancer.

In many cases, a suspected diagnosis of primary biliary cirrhosis (PBC) is made when carrying out a blood test for another, unrelated condition.

Blood tests

Damage to the bile ducts and liver leads to an increase in enzymes (proteins) produced by your liver. The high level of enzymes can be detected by having a blood test.

A diagnosis of PBC can usually be confirmed by checking your blood for a substance called anti-mitochondrial antibodies (AMAs). In PBC, AMAs are produced by the immune system (the body’s natural defence against infection and illness). They are present in 95% of people with PBC.

You may also have a high level of bilirubin in your blood. Bilirubin is a yellow substance produced when red blood cells are broken down. The liver usually “takes up” bilirubin from the blood and it is passed out of your body in urine.

If there is something wrong with your liver or bile ducts, bilirubin cannot be moved into the bowel and leaks back out into the blood. This shows up on a blood test.

Liver biopsy

You may also be referred for a liver biopsy. This involves a small sample of liver tissue being taken so it can be studied under a microscope.

Most liver biopsies can be carried out under local anaesthetic (painkilling medication). The sample is obtained using a long needle and is then examined for evidence of missing or inflamed (swollen) bile ducts.

A liver biopsy is not always necessary to diagnose PBC, which is usually confirmed by the presence of AMAs. However, it can be used to assess the extent of damage to your liver.

Primary biliary cirrhosis (PBC) is a long-term liver disease that damages the small bile ducts in the liver.

This gradually leads to a build-up of bile in the liver, which then damages the organ.

Symptoms of PBC often include:

• fatigue (extreme tiredness)
• itchiness of the skin
• dry eyes and mouth

Read more about the symptoms of PBC.

Bile and bile ducts

Bile is a liquid produced inside the liver that is used by the digestive system to help digest fats and remove waste from the body. It is transported out of the liver into the small bowel through a series of small tubes called bile ducts.

In PBC, for reasons not fully understood, the immune system (the body’s natural defence against infection and illness) gradually damages the bile ducts. Eventually, the damage leads to a blockage that obstructs the flow of bile. The amount of bile in the liver builds up to a dangerous level, causing scarring (cirrhosis).

Who is affected?

PBC is a rare liver condition. In England and Wales, PBC is estimated to affect one in every 3,000 people. However, the rates of PBC in England are higher than in some other parts of the world. The reason for this is unknown.

PBC mainly affects women (about 90% of all cases). The condition usually occurs in people aged 30-65, and is normally diagnosed after a person has reached 40.

The exact causes of PBC, and why it mainly affects women, are unknown.

Read more about the causes of PBC. 

Treating PBC

PBC is usually a progressive condition, which means damage to the liver can steadily get worse over time. The rate at which PBC progresses varies between individuals. It can take decades in many cases.

If not treated, the liver can become damaged to such an extent it no longer works. This is known as liver failure and can be fatal.

There is no cure for PBC, but there are medicines that help slow the progression of the condition and that help relieve the itchiness associated with it. In cases where there is extensive liver damage, a liver transplant may be required.

However, over the last 20 years, the need for liver transplants as a result of PBC has been decreasing. This may be due to the use of a medicine called ursodeoxycholic acid (UDCA).

Read more about how PBC is treated.

The Map of Medicine is used by doctors throughout the NHS to determine the best treatment options for their patients. NHS Choices offers everyone in England exclusive and free access to this cutting-edge internet resource, which lets you see exactly what your doctor sees.

The information in the Map has been approved by the UK’s leading clinical experts, is based on the best available clinical evidence, and is continually updated. To take advantage of this unique resource go to:

Map of Medicine: primary biliary cirrhosis

Around half of all cases of primary biliary cirrhosis (PBC) have no symptoms until extensive liver damage has already occurred. This type of PBC is known as asymptomatic PBC.

Early-stage PBC

In people with symptoms, the most commonly reported symptoms of PBC are:

• chronic fatigue (extreme tiredness) – this is the most common symptom, and many people feel sleepy during the day
• itchy skin (ranging from mild to severe) – this can be widespread or it can only affect a single area, and it may be worse at night when in bed, when in contact with fabrics, when warm, or if pregnant
• dry eyes and mouth

There is often no association between the severity of symptoms and the degree of underlying liver damage. For example, some people with PBC have severe symptoms of fatigue and itchy skin, yet further tests show their liver is not severely damaged. In other people with either no symptoms or mild symptoms, tests can reveal extensive liver damage. As with many aspects of PBC, the reasons for this are unclear.

Advanced PBC

After PBC has caused extensive damage to the liver, there will be additional symptoms as a result of the liver not working as well as it should. These symptoms include:

• jaundice – yellowing of the skin and the whites of your eyes
• build-up of fluid in the legs, ankles and feet (oedema)
• build-up of fluid in your abdomen that can make you look heavily pregnant (ascites) 
• the formation of small fatty deposits on the skin, usually around your eyes (xanthelasmata)
• diarrhoea – your stools may have a particularly unpleasant smell

Progression

Some studies have suggested that people with asymptomatic PBC may survive longer than those with symptoms. However, in general the progression of PBC varies between individuals. Medication can now help delay serious damage to the liver.

There is currently no cure for primary biliary cirrhosis (PBC), so the aim of treatment is to prevent liver damage as much as possible and relieve symptoms, such as itchiness.

Self-help

All types of liver disease, including PBC, can be helped by following some general health advice. You should: 

• quit smoking (if you smoke) 
• avoid obesity by maintaining a healthy weight 
• not drink more than the recommended daily limits of alcohol (3-4 units a day for men, and 2-3 units a day for women)

Not following this advice could speed up the progression of your condition. It may also affect whether or not you can have a liver transplant, if you need one. For example, you may not be offered a liver transplant if you misuse alcohol.

Ursodeoxycholic acid

Ursodeoxycholic acid (UDCA) is a widely used treatment for people with PBC. UDCA is thought to help prevent liver damage by changing the composition of the bile and reducing inflammation (swelling) of the liver. Studies have shown that UDCA can:

• reduce the levels of liver enzymes – these proteins are produced by the liver if the bile ducts and liver are damaged
• reduce the need for a liver transplant

UDCA is thought to work better in the early stages of PBC and is not effective for everyone.

UDCA is usually taken as a single dose at night. It does not improve the other symptoms of PBC, such as itchy skin or fatigue (extreme tiredness).

Once you start taking UDCA, it is likely you will need to take it for the rest of your life. Your liver function may be tested to monitor your condition and you will be assessed after a year to see if you need additional treatment. If you are responding well, it is likely the PBC will remain under control and will not shorten your life span.

Side effects

One possible side effect of UDCA is weight gain. People gain an average of 2.3kg (5lbs) during the first year of taking the medication. After this initial weight gain, most people do not gain any more weight from the drug. Other side effects include:

• loose stools
• thinning hair
• nausea (feeling sick)
• vomiting

Corticosteroids 

PBC sometimes occurs alongside autoimmune hepatitis. This is a very rare cause of chronic (long-term) hepatitis, where the white blood cells attack the liver.

If you have autoimmune hepatitis, you may be treated with corticosteroids as well as UDCA. Corticosteroids are medicines that contain steroids, a type of hormone. They work by suppressing your immune system (the body’s natural defence system) and reducing inflammation.

You will usually be treated with a type of corticosteroid called prednisolone. For more information, see the British Liver Trust: autoimmune hepatitis.

Treating itchiness

Colestyramine, which used to be called cholestyramine, is a medicine widely used to treat the itchiness associated with PBC.

Colestyramine reduces the amount of bile in the blood, which is thought to be the main cause of the itchiness. It usually comes in sachets of a powder that can be dissolved in water or fruit juice. It is a good idea to take the powder with fruit juice, because it has an unpleasant taste.

You may need to take colestyramine for several days before your symptoms begin to improve.

If you are taking UDCA as well as colestyramine, you should avoid taking them at the same time because colestyramine will affect how your body absorbs UDCA. You may need to take UDCA at least one hour before colestyramine, or four to six hours afterwards.

This also applies to any other medicines you are taking. Take them at least one hour before colestyramine, or four to six hours afterwards. Your GP should be able to give you further advice about this.

Constipation is a common side effect of colestyramine. This usually improves once your body gets used to the medicine. Other side effects of colestyramine include:

• diarrhoea
• nausea 
• vomiting 
• bloating

If you are taking colestyramine on a long-term basis, the medicine may affect your body’s ability to absorb vitamins A, D and K from food. In such circumstances, taking additional vitamin supplements may prove beneficial. Your GP can advise you about whether you would benefit from taking vitamin supplements.

Alternative medicines for itching

See your GP if your itchiness does not improve after taking colestyramine. Alternative medicines are available.

For example, rifampicin, which is usually used as an antibiotic, has been used to treat itching in some people. However, it can cause serious side effects, such as liver failure. For this reason, rifampicin is usually only prescribed by a specialist, such as a hepatologist (liver specialist), not your GP.

It is thought that the female hormone oestrogen may make itching worse. Oestrogen is found in some types of hormonal contraceptives, such as the combined contraceptive pill. Therefore, you may wish to consider using a different type of contraceptive, such as condoms.

Oestrogen levels are also increased during pregnancy, so your itching may be worse when you are pregnant.

Managing fatigue

At the moment, no medicines are specifically recommended for treating the fatigue caused by PBC. Your GP may rule out other causes for your fatigue, such as anaemia (a lack of red blood cells) or depression, but fatigue is a difficult symptom to treat. 

Although you should exercise whenever possible, you may need to pace yourself and limit your daily activities to a manageable level in order to cope with your fatigue.

Liver transplant

A liver transplant may be recommended if it is thought that the liver damage may reach the stage where your life is at risk.

Planning for a liver transplant often begins before significant damage to the liver has taken place. There are two reasons for this:

• the average waiting time for a liver transplant is 142 days, so it is important to start searching for a suitable donor as soon as possible
• the better your general state of health, the greater the chance of a successful transplant, so a transplant should ideally be carried out while you are still relatively healthy

Like all organ transplants, liver transplants carry the risk of complications. The most serious complication is that your immune system may reject the donated liver, which could be fatal. You may need to take immunosuppressants (medicine to suppress your immune system) for the rest of your life.

Success rates

The success rates of liver transplants for people with PBC are favourable. For example, one study of 121 people who had a liver transplant for PBC found that:

• 90% were still alive after five years
• 87% were still alive after 10 years
• 80% were still alive after 15 years

In this study, PBC recurred in 15% of people, although some estimates suggest that the condition may recur in up to a quarter of people after a liver transplant.

The itchiness always improves after having a liver transplant, but the fatigue often does not improve.