Primary Biliary Cholangitis

201203_fp_key_visual_master_rgb_50_leber

Primary Biliary Cholangitis

Primary biliary cholangitis (PBC) is a chronic autoimmune disease of the small bile ducts in the liver, which are gradually destroyed by inflammation eventually leading to cirrhosis.

Definition

The term “primary biliary cholangitis”, abbreviated PBC, refers to a chronic, progressive, autoimmune disease of the bile ducts. It is characterized by inflammation of the small bile ducts in the liver. This inflammation is triggered by immune cells that attack the body’s own structures. Because the disease is associated with a backup of bile (cholestasis) in the small bile ducts in advanced stages, it is classified in the category of “cholestatic liver diseases”.

The chronic inflammation in PBC gradually destroys the small bile ducts and eventually begins to attack the surrounding liver tissue as well. If left untreated, the disease may lead to remodeling of liver tissue. This causes the development of fibrosis of the liver (where liver tissue is gradually replaced by connective tissue) and eventually of cirrhosis resulting from scar tissue formation caused by the progressing fibrosis. Because of this final stage, primary biliary cholangitis was previously called primary biliary cirrhosis. The disease can also lead to liver cancer at later stages, which may require a liver transplant.

Current research suggests that primary biliary cholangitis is caused by an interaction between genetic factors and environmental factors. For example, people with a first-degree relative suffering from PBC are themselves at a higher risk of developing the disease. Smokers are also at higher risk.

Primary biliary cholangitis primarily afflicts women, who make up about 90% of all patients. Most patients first develop the disease between the ages of 40 and 60 years old.

The frequency (prevalence) of the disease in Europe is believed to be about 15 per 100,000 people, making primary biliary cholangitis a rare disease. However, the prevalence of the disease appears to be increasing, with higher numbers of new cases (incidence) being reported in Europe and the US in recent years. The reason for this phenomenon is not yet known.

Patients with PBC are disproportionately likely to suffer from other conditions, especially from other autoimmune diseases such as rheumatoid arthritis or an autoimmune thyroid disorder such as Hashimoto’s thyroiditis.

The main symptom of primary biliary cholangitis is itching, which is often intense and mostly affects the arms, legs, and back. Patients also typically report unexplained fatigue or even exhaustion as well as a marked reduction in activity. Furthermore, patients often experience joint pain as well as a sensation of pressure in their upper right abdomen. Dry mouth and eyes are other common and irritating symptoms that are frequently accompanied by reduced tears or saliva, a condition called Sjogren’s syndrome.

Another typical sign of primary biliary cholangitis are yellowish-gray deposits of fat below the skin around the inner corners of the eyelids (xanthelasma).

Symptoms of cirrhosis may occur at later stages of the disease. These may include abnormal skin changes such as spider web-like red spots (spider angioma) or reddening of the palms of the hands (palmar erythema), a yellow discoloration of the skin, mucosa, and eyes (jaundice), water accumulation in the abdomen (ascites), bleeding from varicose veins in the esophagus (esophageal varices) or the stomach, or neurological deficits resulting from a condition called hepatic encephalopathy, which is a functional brain disorder caused by severe liver diseases.

Diagnosis

The first major sign of primary biliary cholangitis is usually elevated levels of liver enzymes in blood tests, especially enzymes that indicate bile duct inflammation and bile backup (called cholestasis parameters). When these findings are made, their cause must always be investigated using other diagnostic procedures.

When a patient is suspected of having primary biliary cholangitis, the doctor will first try to confirm this diagnosis by asking the patient about his or her current symptoms and medical history. The questions will focus on the typical symptoms of PBC and when they first occurred. The doctor will also ask about risk factors for liver diseases, such as medications (including naturopathic medicines) or alcohol consumption.

There will also be questions about symptoms that may suggest a patient already has cirrhosis of the liver, such as whether the abdomen is enlarged or body weight has increased.

The medical history discussion is usually followed by a detailed physical examination, including looking for skin abnormalities, xanthelasma, or scars from itching.

If a doctor suspects that a patient might have primary biliary cholangitis, blood tests will be ordered. The results of these tests are a major factor in diagnosing PBC. The disease is associated with increases in the levels of enzymes that are linked to cholestasis: alkaline phosphatase (AP), gamma-glutamyl transferase (GGT), and sometimes the level of total bilirubin.

For an in-depth diagnosis of PBC, blood tests also look at specific proteins called autoantibodies, such as anti-mitochondrial antibodies (AMA), that are present in over 90% of PBC patients. AMA are antibodies that circulate in the bloodstream and target specific components of the cell that produce energy (mitochondria). Although they do not cause PBC themselves, the presence of these autoantibodies together with elevated levels of AP and GGT are clear signs of PBC. Detection of these autoantibodies is considered near proof of primary biliary cholangitis. Class M immunoglobulins are also frequently elevated in PBC patients.

In addition to laboratory tests, imaging procedures play an important role in diagnosing primary biliary cholangitis. The most common procedure is an ultrasound examination, which allows doctors to check whether fibrosis or even cirrhosis has already developed. During the early stages of PBC, the liver still appears healthy and unchanged. However, the advanced stage of the disease is characterized by remodeling of liver tissue that can be detected by ultrasound. An ultrasound examination is safe and easy to perform and does not require exposure to radiation. It is also an important procedure to rule out other potential causes of the backup in bile, such as gallstones, cancer, or bile duct constrictions.

Doctors can gather even more detailed information using an examination technique called transient elastography. This procedure analyzes the stiffness and percentage of connective tissue in the liver in order to determine the extent of fibrosis.

If a suspected diagnosis of PBC still has not been confirmed, a tissue sample (biopsy) in rare cases is collected from the liver and examined under a microscope. This method allows the small bile ducts to be examined directly for damage.

A liver biopsy can also clarify whether there may be an overlap with another liver disease such as autoimmune hepatitis.

Treatment

It is usually not possible to cure primary biliary cholangitis. Nevertheless, medication can delay the progression of PBC, and normal life expectancy can be achieved if patients respond well to the treatment.

Primary biliary cholangitis is typically treated with ursodeoxycholic acid, abbreviated as UDCA. This is a natural bile acid that is usually only present in the human body at small concentrations. Taking it helps bile move through the liver and ducts, inhibits inflammation, and stops the formation of connective tissue (fibrosis), all of which can prevent the disease from progressing to cirrhosis. Most people tolerate UDCA well. It must be taken permanently and can have such a positive impact on the prognosis of patients with a positive biochemical response (meaning a major improvement in blood test levels), that they achieve a normal life expectancy. The protective effects of UDCA are strongest if therapy is started early in the course of the disease. Response to UDCA treatment should be verified by laboratory tests after no later than 12 months. UDCA is dosed depending on body weight and as treatment needs to be performed longterm, it is important to evaluate correct dosing by weighing in a regular fashion.

Patients who do not adequately respond to ursodeoxycholic acid are usually prescribed medications containing the synthetic bile acid obeticholic acid, which also stimulates bile flow.

Other medications used to treat PBC target the symptoms of the disease. These are frequently drugs that reduce itching. The use of artificial tears can help alleviate the symptom of dry eyes.

Without medication, the disease may damage the liver severely enough to require liver transplantation.

An active lifestyle with regular physical activity and relaxation exercises can have beneficial effects on general well-being and fatigue. A balanced diet with sufficient variety and adequate sleep can also be helpful for people with PBC.

Outlook and prognosis

The outlook for PBC depends on a patient’s age and gender, on the stage of the disease at the time of diagnosis, and on how well the patient responds to PBC therapy. If primary biliary cholangitis is detected at an early stage and treated thoroughly and successfully, PBC patients can maintain a normal life expectancy. On the other hand, if the disease remains untreated, there is a high risk that the liver will become increasingly injured and eventually develop cirrhosis, which often requires liver transplantation. Receiving a new liver theoretically cures a patient of PBC. Nonetheless, PBC may also develop in the newly-transplanted liver, which is why preventive UDCA therapy is usually continued after transplantation.