Primary Biliary Cirrhosis Causes, Symptoms, Diagnosis, Treatment, Prevention

Primary Biliary Cirrhosis Causes, Symptoms, Diagnosis, Treatment, Prevention


What is primary biliary cirrhosis (PBC)?


Primary biliary cirrhosis is a liver disease that slowly destroys the bile ducts in the liver. Bile, a substance that helps digest fat, leaves the liver through these ducts. When the ducts are damaged, bile builds up in the liver and damages liver tissue. Over time, the disease can cause cirrhosis and may make the liver stop working.

Primary biliary cirrhosis is diagnosed through laboratory tests, x-rays, and in some cases, a liver biopsy (a simple operation to remove a small piece of liver tissue). Treatment may include taking vitamin and calcium supplements, hormone therapy, and medicines to relieve symptoms. A liver transplant may be necessary if the liver is severely damaged.

Read more: Primary Pulmonary Hypertension Causes, Symptoms, Diagnosis, Treatment

Causes of primary biliary cirrhosis


The exact cause of PBC is unknown, but it may be related to a problem with the immune system, which is the body's natural defense system. 

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

Primary Biliary Cirrhosis Risks


A risk factor is something that increases your chance of getting a disease or condition.

Risk factors include:

  • Gender: Women are nearly ten times as likely as men to develop PBC.
  • Family History: If someone in your family has PBC, your have a slightly higher risk.
  • Viral hepatitis: Both Hepatitis B and Hepatitis C have also shown to be contributing factors.
If anyone in your family has been diagnosed with PBC, or has other liver problems, or if you have hepatitis B or C, tell your doctor.

What are the symptoms of Primary Biliary Cirrhosis?

Many people who have primary biliary cirrhosis do not have symptoms. When symptoms do occur, they may include:

  • Itching (pruritus).
  • Fatigue.
  • Yellowing of the skin and the white part of the eyes (jaundice).
  • Discomfort in the upper right part of the abdomen.
  • Dry eyes and mouth.
  • Vaginal dryness.
  • Arthritis
With more advanced liver damage, people may have complications related to cirrhosis such as:

  • Fluid buildup in the abdomen (ascites).
  • Bleeding of enlarged veins in the esophagus, stomach, and rectum (variceal bleeding).
  • Premature thinning of the bones (osteoporosis).

Diagnosing primary biliary cirrhosis 


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.

How is Primary Biliary Cirrhosis treated?


Treatment for primary biliary cirrhosis is difficult, because the immune system appears to be involved. As with other forms of cirrhosis, treatment focuses on reducing symptoms, preventing and treating the complications of the disease, and preventing other conditions that may cause additional liver damage.

The medicine ursodiol is usually given soon after a diagnosis of primary biliary cirrhosis. Ursodiol helps move bile out of the liver and into the small intestine. If it is used early enough, ursodiol can improve liver function and may keep you from needing a liver transplant. The medicine may also help you live longer.1

Medicines such as cholestyramine, rifampicin, or naltrexone may be used to help with itching caused by PBC.

If you have fatigue, your doctor will try to find the cause of your tiredness. It may not be caused by PBC. Some medicines have been tried to help with fatigue in PBC, but none have been proved to work well.

PBC can also cause dry eyes and mouth. The best way to help dry eyes is to use eye drops (artificial tears) when your eyes feel dry. A dry mouth can be helped by chewing gum or hard candy to increase saliva. You can also use a saliva substitute. If that doesn't help, there are some medicines that can be used.

Because people with PBC have a high risk of getting osteoporosis, you should have periodic bone mineral density scans. Your doctor may suggest that you take calcium and vitamin D supplements, and perhaps a medicine called a bisphosphonate.

Liver transplantation may be the treatment of choice for people who have end-stage primary biliary cirrhosis, although primary biliary cirrhosis can recur after a liver transplant.

What treatments are used for the complications of the cirrhosis in Primary Biliary Cirrhosis? 


Edema and ascites 


Retention of salt and water can lead to swelling of the ankles and legs (edema) or abdomen (ascites) in patients with cirrhosis. Diuretics are medications that work in the kidneys to combat retention of fluid by eliminating salt and water into the urine. A combination of the diuretics spironolactone (Aldactone) and furosemide can reduce or eliminate the swelling in most people. During treatment with diuretics, it is important to monitor kidney function by measuring serum levels of blood urea nitrogen (BUN) and creatinine to determine if the doses of the diuretics are safe. Sometimes, when the diuretics do not work, a long needle is used to draw out the fluid directly from the abdomen (a procedure called paracentesis).

Bleeding from varices 


If large varices (distended veins) develop in the esophagus or upper stomach or any episodes of bleeding from varices have occurred, physicians should consider specific therapy for the varices. Treatment with propranolol (Inderal), a drug in a class called beta-blockers, is effective in preventing initial bleeding or rebleeding from varices in patients with cirrhosis. This drug, however, has not been proven to prevent bleeding in patients with portal hypertension who do not have cirrhosis.

Other methods are available to prevent or treat varices. These methods include:

  • Procedures done during upper endoscopy
  • Other drugs [for example, octreotide
  • Other non-surgical procedures
  • A surgical operation to create a shunt (passage) from the high-pressure portal vein to veins with lower pressure can eliminate blood flow into the varices. It is appropriate to consider such a surgical shunt for patients with PBC and portal hypertension who do not have cirrhosis or have only early cirrhosis. The hazards of shunt surgery in these patients would be less than those in patients with advanced cirrhosis.

Hepatic encephalopathy 


PBC patients with an abnormal sleep cycle, impaired thinking, odd behavior, or other signs of hepatic encephalopathy usually should be treated with a low protein diet and oral lactulose. Dietary protein is restricted because it is a source of the toxic compounds present in hepatic encephalopathy. The lactulose, which is a liquid medication, traps the toxic compounds in the colon. Consequently, they cannot be absorbed into the blood stream and cause the symptoms of encephalopathy. To be sure that adequate lactulose is present in the colon at all times, the patient should adjust the dose to produce 2 to 3 semiformed bowel movements a day. If symptoms of encephalopathy persist, the oral antibiotics, neomycin or metronidazole (Flagyl), can be added to the treatment regimen.

Hypersplenism 


The blood filtration function of an enlarged spleen usually results in only mild reductions of red blood cells (anemia), white blood cells (leukopenia) and platelets (thrombocytopenia) that do not require treatment. Severe anemia, however, may require blood transfusions or treatment with erythropoietin or epoetin alfa (Epogen, Procrit), a hormone that stimulates production of red blood cells. If the numbers of white blood cells are severely reduced, another hormonal drug, called granulocyte-colony stimulating factor (G-CSF) is available to increase the white blood cells. An example of an available G-CSF drug is filgrastim (Neupogen).

No FDA-approved medication is available yet to increase the number of platelets. As a necessary precaution, patients with low platelets should not use aspirin or other non-steroidal anti-inflammatory drugs (NSAIDS) since these drugs can hinder the function of platelets. If a low number of platelets is associated with significant bleeding, transfusions of platelets usually should be given. Surgical removal of the spleen (called splenectomy) should be avoided, if possible, because of the risk of excessive bleeding during the operation and the risk of anesthesia in advanced liver disease.

What precautions should be taken?


The liver is the body's most important drug-metabolizing organ so medications must be taken with caution. It is wise to consult with your physician before taking any medication, including pain relievers, over-the-counter drugs and herbal remedies. Patients should eat a healthy and balanced diet. Alcohol may increase damage to the liver and should not be consumed regularly.

What is the role of liver transplantation in Primary Biliary Cirrhosis? 


Liver transplantation is a life saving operation for those patients with PBC who are at risk of premature death due to liver failure or the complications of cirrhosis and portal hypertension. The Mayo Risk Score provides an accurate estimate of the future outcome (prognosis) for patients, regardless of whether they are being treated with ursodeoxycholic acid. The United Network for Organ Sharing (UNOS) permits patients with PBC to be listed for a liver transplant once their estimated survival with PBC for an additional year is 95% or less. It is recommended that physicians calculate the Mayo Risk Score at least yearly in all patients with PBC who have cirrhosis.

Most PBC candidates for transplantation have advanced cirrhosis with decompensated liver disease, which also is referred to as liver failure. Decompensated liver disease means that the patients have low levels of serum albumin and blood clotting factors made in the liver and complications of portal venous hypertension such as ascites, variceal bleeding, encephalopathy, or hypersplenism. Patients are classified as having decompensated cirrhosis whether or not the complications respond to medical therapy.

Rarely, before advanced cirrhosis develops, transplantation of the liver is warranted in a few clinically disastrous situations in PBC. Examples of such situations include recurrent fractures due to advanced osteoporosis or severe, debilitating itching unrelieved by any medical therapy, and even more rarely, the hepatopulmonary syndrome (breathing difficulty in advanced cirrhosis). The regional review committees of UNOS accept applications for transplantation in these special circumstances and decide on a patient-by-patient basis if liver transplantation is indicated.

Are lifestyle changes required for Primary Biliary Cirrhosis sufferers?


There is a healthy way to live with a chronic disease and patients with PBC should be encouraged to maintain an active lifestyle under the supervision of their doctor.

It is important for PBC patients to realize that support is available that may help them to improve their quality of life.