Primary Biliary Cirrhosis (PBC)

The liver which is the largest, solid, internal organ consists mainly of hepatocytes (liver cells) and bile ducts. Primary biliary cirrhosis (PBC) is a slowly progressive and therefore chronic form of liver disease which attacks the bile ducts within the liver. Bile ducts are channels through which bile produced in the liver flows. PBC is an autoimmune condition – the body’s own immune system attacks the bile ducts. Specifically, it is the cells which line these ducts which are targeted by the immune system. This causes the flow of bile within these ducts to be disrupted (this is called cholestasis). As a result, this forces the bile acid to leak from the ducts into the surrounding liver tissue. This causes inflammation and further damage to the liver, resulting eventually in scar tissue formation and therefore cirrhosis. Compounding this situation is the fact that the elimination of many toxins by the liver through bile is also reduced. These toxins build up inside the liver causing further problems. The whole process to the stage of cirrhosis usually takes several years.

However, not everyone who has PBC will go on to develop cirrhosis. This is because the liver is usually able to regenerate itself without scarring. But if the process of cholestasis and therefore liver damage is continuous, scarring may develop leading to cirrhosis.

What Is Bile?

Bile is a greenish acidic fluid produced by liver cells. It is then excreted by these cells into a system of tiny vessels within the structure of the liver. These are bile ducts. The smaller ducts merge to form larger ducts within the liver (intrahepatic bile ducts) which also merge to form the common bile duct. This leads to the gallbladder which stores bile. This fluid is excreted into the small intestines to help digest fatty foods and also aids in the absorption of vitamins A, D, E and K from the gut. Because bile is acidic, it is irritating to tissues which are not designed to be in contact with it. The process of cholestasis which causes leakage of bile into liver tissues therefore causes an inflammatory response in the liver.

The Causes of Primary Biliary Cirrhosis

The exact cause for why the immune system targets and destroys its own cells is still not understood. But there does seem to be a genetic link, i.e. autoimmune disorders can run in families and therefore be inherited. The trigger for such autoimmune disease has been speculated to be viral infections, drugs, chemicals, stress or other unknown factors. PBC can be associated with pregnancy, starting either during or shortly after pregnancy. PBC may also be associated with smoking. It does not seem to be related to excessive alcohol consumption.

PBC like many autoimmune conditions is more prevalent in women than men. If one family member has this condition, others are then also more likely to develop it. This applies especially to female members of the family. Women are also most likely to be aged between 30 and 55 years old at the onset of this disease.

For reasons which remain elusive, there seem to be parts of the world where PBC is more common. Scandinavia, Scotland and North England seem to have the highest prevalence, although PBC suffers can be found anywhere in the world.

Symptoms And Signs Of Primary Biliary Cirrhosis

Many patients with PBC have no symptoms and in fact, many individuals will never become aware that they even have this condition. Others however can go on to develop many of the symptoms of liver disease. The possible symptoms and signs include;

• none: liver disease may be found incidentally,
• a feeling of being unwell,
• fatigue,
• nausea,
• vomiting,
• diarrhoea,
• weight loss,
• dry eyes and mouth,
• red or pink, blotchy, mottled patches on the palms of hands (palmer erythema),
• abnormal small blood vessels on the surface of the skin, mainly on the face, chest and arms (spider naevi),
• abdominal pain or discomfort,
• itching of skin,
• enlargement of the liver (hepatomegaly),
• jaundice: yellowing of the skin and whites of the eyes,
• passing dark urine: associated with jaundice,
• passing pale or clay coloured stools: associated with jaundice,
• bruising,
• bleeding from any site e.g. gums, nose, wounds, rectum, vagina,
• abdominal distension from fluid collecting in the abdomen (ascites),
• vomiting of blood (haematemesis), from oesophageal varices,
• confusion and an altered level of consciousness (hepatic encephalopathy),
• coma,
• death.

The two commonest symptoms tend to be itching and lethargy.

Diagnosing Primary Biliary Cirrhosis

Initially, testing is carried out in the same way as described for the many other liver conditions in this guide. This includes blood tests for liver function tests (LFT), clotting (INR) and several other blood tests. These may be followed by ultrasound scanning to visualise the liver and bile ducts. More specialised blood tests may be required that may suggest an autoimmune cause. These include an “auto-antibody” screen. Specific examples of this include; anti-nuclear antibodies (ANA) and smooth muscle antibodies (SMA). If these are present and elevated, then the possibility of an autoimmune cause for the liver damage has to be considered. PBC sufferers are often noted to have the presence of a specific antibody called anti-mitochondrial antibody (AMA). If patients test positive for AMA, PBC should be suspected.

But the main method used to make sure of the diagnosis is liver biopsy. This can be done in the following ways;

1. Percutaneous Liver Biopsy

This can be done unguided or guided by ultrasound. After the position of the liver has been established, a local anaesthetic is injected into the skin. This is usually done over the upper right side abdomen or between the lower ribs. After the skin is numb, the doctor makes a small incision into the skin and inserts a needle (sometimes called a Trucut) into the wound. This is inserted into the liver and removed. It will contain a small sample of liver tissue.

2. Laparoscopic Liver Biopsy

This is usually done under general anaesthetic. With this approach, a small thin tube containing a light and camera is inserted into the abdomen. Through a separate small incision, another instrument is used to target specific areas of the liver to collect samples which are then removed.

3. Transjugular Liver Biopsy

This approach is sometimes used when a patient has severe clotting problems or when there is fluid in the abdomen. It is done in an X-ray unit. A catheter is inserted into a vein in the neck. This is then guided to the liver. A biopsy needle is then passed through the catheter until it travels down to the liver. A sample of liver tissue is then obtained and removed. This is generally a less risky approach compared to the percutaneous approach.

Treatment of Primary Biliary Cirrhosis

Presently, there is no cure for PBC. But different medicines are used to control symptoms and therefore decrease the level of liver damage. Some medicines help to reduce inflammation while others try to dampen the immune response and so halt the destruction of bile ducts. Finally, the symptoms of PBC can be alleviated using other medicines. Examples of these are given below;

1. Drugs That Suppress PBC

• Ursodeoxycholic acid: this helps to reduce cholestasis – it improves the flow of bile acid through the ducts, thereby reducing leakage and damage to surrounding liver cells,

• Immunosuppressants: these reduce the immune response to halt the disease. Examples include cyclosporine.

2. Treatment Of Symptoms

• Corticosteroids (Prednisolone): these tablets reduce inflammation and reduce symptoms. But use of steroids longer term can have many problems such as osteoporosis (thinning of the bones),

• Cholestyramine (Questran): this is commonly used to reduce the symptom of itching. However, it can cause a disturbance of bowel function and bloating.

• Anti-histamines: these can also be used for itching although often, are used only for sedation,

• Ultraviolet Light Therapy: can be used for itching,

• Treatment of Sicca Syndrome: this is when patients with PBC develop dry eyes, mouth and possibly other areas including vaginal dryness. Various treatments such as artificial tears and saliva and lubricating jellies can be used depending on the location.

3. Other Treatments

• Vitamin Supplements: these may be useful, especially for those with reduced appetite or poor diet leading to weight loss and muscle wasting,

• Calcium Supplements: to help prevent osteoporosis

Finally, for a small minority of PBC sufferers, liver function continues to deteriorate. In these individuals, careful planning for possible liver transplantation, well in advance of complete liver failure is the best option. The longer term outlook for even this group of patients is good.

Complications of Primary Biliary Cirrhosis

Apart from the liver symptoms and signs already discussed above, there may be other complications which may arise as a consequence. These include:

• raised cholesterol; as there is less bile available to breakdown fats in food the level of cholesterol in blood can increase. This can lead to an increased risk of heart disease.

• osteoporosis; both liver disease and certain treatments for liver disease such as steroids can lead to an increased likelihood of osteoporosis. In addition, as osteoporosis tends to occur mainly in post-menopausal women and PBC is a condition which mainly affects women in their middle years, osteoporosis can be a particular problem.

• vitamin deficiency; this also occurs due to the lack of bile being excreted into the intestines resulting in a deficiency of fat soluble vitamins.

• the onset of other autoimmune conditions; these include thyroid disease and rheumatoid arthritis.

From Surgery abroad with Globe Health Tours.