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Medical Author:

John M. Vierling, MD, FACP

John M. Vierling, MD, FACP

John M. Vierling M.D. is Professor of Medicine and Surgery at the Baylor College of Medicine in Houston, Texas, where he also serves as Director of Baylor Liver Health and Chief of Hepatology. In addition, he is the Director of Advanced Liver Therapies, a center devoted to clinical research in hepatobiliary diseases at St. Luke's Episcopal Hospital. Dr. Vierling is board certified in internal medicine and gastroenterology and a Fellow of the American College of Physicians.

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Medical Editor:

Leslie J. Schoenfield, MD, PhD

Leslie J. Schoenfield, MD, PhD

Dr. Schoenfield served as associate professor of medicine and consultant in gastroenterology on the faculty of the Mayo Clinic for seven years. He became a professor of medicine in residence at UCLA from 1972 to 1999 (now emeritus). He was the director of gastroenterology at Cedars-Sinai Medical Center in Los Angeles for 25 years, where he received the chief resident's teaching award, the president's award, and the pioneer of medicine award.

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In this Article

• What is PBC?
• What is the scope of the problem?
• What is the cause of PBC?
• What are the symptoms and physical findings in PBC?
• What manifestations are specifically due to PBC itself?
• What are the manifestations of the complications of cirrhosis in PBC?
• What are the manifestations of diseases associated with PBC?
• What are risk factors for PBC?
• How is PBC diagnosed?
• What is the role of blood tests?
• What is the role of testing for antimitochondrial antibodies?
• What is the role of imaging tests?
• What is the role of liver biopsy?
• What are the criteria for a definitive diagnosis of PBC
• What is the course of natural progression in PBC?
• What are the sequential clinical phases of PBC?
• What is the role of mathematical models in predicting the outcome (prognosis) in PBC?
• What about pregnancy in PBC?
• Patient Comments: Primary Biliary Cirrhosis - Symptoms
• Patient Comments: Primary Biliary Cirrhosis - Diagnosis
• Find a local Gastroenterologist in your town
• Primary Biliary Cirrhosis Index

Xanthomas

Cholesterol may deposit in the skin around the eyes or in skin creases of the palms, soles, elbows, knees, or buttocks. Collectively, these waxy, raised deposits are called xanthomas. Such deposits around the eyes are also referred to as xanthalasma. Xanthomas are more common in PBC than in any other liver diseases associated with cholestasis. Most xanthomas do not cause symptoms, but those on the palms sometimes can be painful. Rarely, xanthomas deposit in nerves and cause a neuropathy (disease of the nerve). This neuropathy is characterized by abnormal sensation in the parts of the body, most often the limbs, supplied by the affected nerves.

Although elevated levels of cholesterol in the blood are common in PBC and other liver diseases with cholestasis, xanthomas are found in only 25% of patients at the time of diagnosis. Xanthomas tend not to occur until the serum cholesterol rises to very high levels, for example, above 600 mg/dL. Xanthomas tend to spontaneously disappear in patients with advanced liver disease due to impaired production of cholesterol by the damaged liver. Importantly, the high levels of serum cholesterol in PBC do not seem to increase the risk of heart disease because the composition of the cholesterol is different from the usual cholesterol (atypical) and does not easily deposit in blood vessels.

Malabsorption of fat and fat-soluble vitamins

As the amount of bile acids entering the gut decrease with increasing cholestasis, patients can loose the ability to absorb all of the fat present in their diet. This reduction in fat absorption, called malabsorption, occurs because the bile acids are needed for the normal intestinal absorption of fat. So, when advanced cholestasis prevents adequate amounts of bile acids from reaching the small bowel, the absorption of dietary fat and of the vitamins A, D, E and K is reduced. As a result, undigested fat passing into the large intestine causes diarrhea, while continuing malabsorption of fat can lead to weight loss and vitamin deficiencies. A laboratory measurement of the amount of fat in the bowel movements can reveal whether the dietary fat is being absorbed normally or not.

Vitamins A, D, E, and K, referred to collectively as the fat-soluble vitamins, are absorbed from the gut in the same way that dietary fat is absorbed. Therefore, deficiencies of these vitamins can occur in advanced cholestasis. Also, bear in mind that some of the other conditions associated with PBC, such as pancreatic insufficiency, celiac sprue, and scleroderma with bacterial overgrowth, can also lead to malabsorption of fat and of the fat-soluble vitamins. Prior to the development of jaundice, however, deficiencies of vitamins A and E actually occur in only a minority of PBC patients. Vitamin A deficiency causes decreased vision in the dark. Vitamin E deficiency can cause abnormal skin sensations or muscular weakness due to its effects on the nerves that extend from the spinal cord.

As already noted, deficiency of vitamin D results in osteomalacia (bones with inadequate amounts of calcium deposited in them.) Deficiency of vitamin K reduces the liver's production of blood clotting proteins and consequently, causes a tendency to bleed easily. Also, the resulting deficiency of clotting factors makes a blood test called the prothrombin time (blood clotting test) to become abnormal. Prothrombin is a clotting factor that is produced in the liver and needed for the normal clotting of blood. It is important to recognize that the liver damage itself also can impair production of blood clotting factors and cause easy bleeding and an abnormal prothrombin time.