Primary Biliary Cholangitis (Primary Biliary Cirrhosis)

By Stephen Holt, MD, PhD, FACP

• What is Primary Biliary Cholangitis?
• Causes
• What Are the Risk Factors?
• Signs and Symptoms
• How is it Diagnosed?
• Treatment
• Are There Alternative Treatments?
• What is the Long Term Prognosis?

What is Primary Biliary Cholangitis?

Primary biliary cholangitis (PBC), formerly known as primary biliary cirrhosis, is a chronic disease of progressive irritation and inflammation of the bile ducts in the liver. This irritation and inflammation blocks the flow of bile from the liver. Bile is a fluid produced in the liver, essential for the proper digestion of fats which also helps rid the body of worn-out red blood cells, cholesterol and toxins. Eventually, the blockage of bile causes a buildup of harmful substances in the liver which can lead to liver damage, namely cirrhosis (a condition in which the liver slowly deteriorates and malfunctions). PBC is considered to be an uncommon disease, but not rare.

Causes

The cause of PBC is unknown. It is believed it may be an autoimmune disease in which the immune system attacks the body’s own tissues. There is also the possibility that heredity, environmental factors, and infection may play a role in the development of PBC; however, to date, no studies have conclusively shown that infection is the cause of PBC nor that it is triggered by a self-limited infection.

Also, PBC is not associated with infection by any of the known hepatitis viruses. Furthermore, none of the new viruses that may cause liver diseases have been found primarily or exclusively in patients with PBC.

What Are the Risk Factors?

The following factors may increase the risk of primary biliary cholangitis:

• Gender – It predominantly affects women.
• Age – Middle-aged people between the ages of 30 and 60 are most frequently diagnosed. No known cases have ever been diagnosed in children.
• Family History – Having a family history increases the risk of developing the disease.

Signs and Symptoms

Many people with PBC do not exhibit symptoms at diagnosis as symptoms usually come on gradually.  The most common symptoms are:

• Itchy skin (pruritus)
• Fatigue
• Dry eyes and mouth (sicca syndrome)

Once the disease has progressed other symptoms occur such as:

• Jaundice (yellowing of the whites of the eyes and the skin) – Jaundice is a common sign of advanced liver disease.
• Edema and Ascites – Swelling in the feet and ankles (edema) caused by fluid retention and fluid retention in the abdomen (ascites).
• Skin discoloration (hyperpigmentation) – Darkened skin due to inadequate bile flow.
• Xanthomas – (waxy raised deposits in the skin) – Fatty cholesterol may deposit in the skin around the eyes or in skin creases of the palms, soles, elbows, knees, or buttocks once blood cholesterol reaches very high levels. However, not all people with PBC develop xanthomas.
• Intestinal problems – Since bile is essential to the digestion and absorption of fats, PBS can cause intestinal problems which include diarrhea and fatty stools (steatorrhea) resulting in weight loss in the late stages of the disease.
• Metabolic bone disease – Patients with PBC may experience pain in the bones of their legs, pelvis, back (spine), or hips. This bone pain can come from one of two bone diseases, osteoporosis (sometimes referred to as thin bones) or osteomalacia (soft bones).

How is it Diagnosed?

Because many people with primary biliary cholangitis do not have symptoms when they’re initially diagnosed, routine blood tests or an evaluation for another condition often brings awareness of the condition to the doctor.

If PBC is suspected, the following tests can help in making a diagnosis:

• Liver function tests – Because certain liver enzymes are elevated in most individuals with PBC, namely alkaline phosphatase, blood tests are done to check the function of the liver, to check enzyme levels that may indicate liver disease in general and particularly bile duct injury.
• Anti-mitrochondrial antibodies (AMA) – A very reliable test used to determine the presence of  PBC because most people with it have anti-mitrochondrial antibodies – antibodies that target enzymes in the mitochondria. Mitochondria are the primary energy producers of the body which are found in every cell. Antibodies are proteins in the blood that help destroy bacteria and other harmful pathogens. A small percentage of people with primary biliary cholangitis don’t have AMAs so a false positive test result is possible. Results are positive in about 95% of cases.
• Abdominal ultrasound – This is a non-invasive test which uses high frequency sound waves to create precise images of organs inside the body including the bile ducts which may be inflamed.
• Magnetic resonance imaging (MRI) and magnetic resonance elastography (MRE) – MRI is a noninvasive medical test that assists doctors in diagnosing and treating medical conditions. MRI uses a powerful magnetic field, radio frequency pulses and a computer to produce detailed pictures of organs, soft tissues, bone and virtually all other internal body structures without using x-rays. MRE is an imaging technique used to measure the elasticity of tissue by gently shaking the tissue in a magnetic resonance imaging (MRI) machine. MRE works by measuring the wavelength of the vibrations sent through the tissues. MRE technology works by combining traditional magnetic resonance imaging with low-frequency sound waves thereby possibly avoiding the need for a liver biopsy which is more invasive.
• Liver biopsy – This procedure entails the removal of a small sample of liver tissue through a small incision using a thin needle. The liver sample is then studied in a laboratory to confirm the diagnosis and/or the extent of the disease. A liver biopsy is invasive, costly and, is affected by sampling error.

Treatment

Because PBC is not curable, the main focus of treatment is to relieve symptoms, slow progression of the disease and prevent complications.

Methods to relieve symptoms

For intense itching experienced by those with PBC the following methods are used:

• Cholestyramine and Colestipol – Two cholesterol lowering drugs that are extremely effective in controlling the itching commonly experienced by people who have PBC, Cholestyramine and Colestipol unfortunately, have certain side effects for some people. Both drugs may interact with other medications and both drugs interfere with the body’s metabolism of UDCA (ursodeoxycholic acid, a bile acid that helps move bile through the liver), hormones, some other drugs and vitamins.
• Rifampin – This medication is usually prescribed for people who can’t tolerate the side effects of Cholestyramine and Colestipol. This slow acting drug doesn’t work for everyone and can take up to a month to be effective.
• Opioid antagonists – Studies are being done to determine whether opioid antagonists are effective in relieving severe itching. Although some of these drugs appear to be effective, it is necessary for them to be administered intravenously and may cause withdrawal symptoms.
• Liver transplant – A last resort to relieve the intense itching experienced by some people with PBC for whom medications do not work.

With the goal of slowing progression of PBC and prolonging survival, the following treatments are used:

• Ursodeoxycholic acid (UDCA) – Commonly considered the first line of therapy, UDCA, also known as ursodiol (Actigall), is a bile acid that improves the livers ability to function by moving bile through the liver. When administered early in the disease, it may prolong life and delay the need for a liver transplant. Some, not all people may experience side effects from UDCA which include diarrhea, weight gain and hair loss.
• Other drugs – Many drugs have been studied for use in the treatment of primary biliary cholangitis but because of severe side effects, lack of effectiveness or proof of long term benefits, UDCA is the only accepted treatment for primary biliary cirrhosis at this time.
• Liver transplant – When the liver begins to fail because treatment no longer works, liver transplant has been proven to prolong life. Individuals who have PBC often do very well after a liver transplant, although the disease can return.

Because people who have PBC are at risk of developing complications, certain tests, precautionary measures, and lifestyle changes may be necessary. For example, a bone mineral density scan to detect osteoporosis (thinning of the bones) may be performed. In the case where osteoporosis has been detected, treatment with bisphosphonates may be necessary. Bisphosphonates are a group of drugs that can inhibit bone breakdown and even increase bone mass. Taking calcium supplements and vitamin D supplements, as well as eliminating smoking and getting weight bearing exercise may be beneficial.

Vitamin deficiencies are another complication, so injections of vitamin K and water-based oral supplements of vitamins A, D and E may be recommended.

Are There Alternative Treatments?

Maintaining a healthy lifestyle and generally taking good care of one’s overall health may be helpful in alleviating some of the symptoms and preventing some of the complications that can occur in people who have PBC.

Some recommendations include:

• Eat a reduced-sodium diet to prevent risk of tissue swelling and of accumulating fluid in the abdomen (ascites).
• Exercise and take calcium and vitamin D supplements to help reduce risk of developing osteoporosis.
• Avoid drinking alcohol, a known toxin to the liver.
• Practice good skin care to reduce itching.
• Use artificial tears to help reduce dry eyes.
• Quit smoking. Smoking may speed up the rate of liver scarring.
• Try to avoid stress as stress tends to make symptoms worse.
• Check with your doctor before starting new medications or dietary supplements due to possible sensitivity and/or side effects.

What is the Long Term Prognosis?

Because doctors are able to diagnose primary biliary cholangitis very early, prognosis is much better than it was in the past since treatment can begin before severe damage occurs to the liver.

Studies are continuing to be done to find the cause of PBC and to understand this disease which has been known for more than 100 years. Through drug therapy trials, new and better treatments will be developed to control liver damage and lessen the symptoms.

This information is for educational purposes only and should not be used in any other manner. This information is not intended to substitute for informed medical advice. You should not use this information to diagnose or treat a health problem or disease without consulting with a qualified health care provider.

About the Author

Stephen Holt, MD, PhD, FACP

Stephen Holt, M.D. is a Distinguished Professor of Medicine NYCPM (Emerite) and a medical practitioner in New York State. He has published many peer-review papers in medicine and he is a best-selling author with more than twenty books in national and international distribution. He has received many awards for teaching and research. Dr. Holt is a frequent lecturer at scientific meetings and healthcare facilities throughout the world. He is a best selling author and the founder of the Holt Institute of Medicine.