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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

The key blood test abnormality in PBC and all liver diseases associated with cholestasis is an elevated alkaline phosphatase enzyme level in the blood. The finding of a concurrent elevation of the gamma glutamyl transpeptidase (ggt) blood level proves that the elevated alkaline phosphatase is from the liver, rather than from bone (another source of alkaline phosphatase). Other liver enzymes, such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT), may be either normal or only slightly elevated at the time of diagnosis. As the duration of disease increases, both of these liver enzymes (the aminotransferases) usually become elevated to a mild to moderate degree, while the alkaline phosphatase can become very high. For more information about liver blood tests, please read the Liver Blood Tests article.

Other blood tests may also be helpful in the diagnosis of PBC. For example, serum immunoglobulin M (IgM) is frequently elevated. Also, just about all patients with cholestasis develop increased cholesterol levels (as noted previously), and some also develop elevated triglycerides. Moreover, testing the levels of these fats (lipids) can identify patients who might form cholesterol deposits in the skin or nerves. (See the section on xanthomas above.)

AMA are detectable in the serum in 95 to 98% of patients with PBC, as noted earlier. The most economical test for AMA applies diluted samples of a patient's serum onto tissue sections from rat stomach or kidney in the laboratory. (Remember that the mitochondria are present in all cells, not just the cells of the liver and bile ducts.) Serum antibodies that attach (bind) to mitochondrial membranes within the tissue cells can then be observed with a microscope. The most dilute sample of serum showing this binding reaction is reported, using the term titer. The titer indicates the most dilute serum sample that reacts with the tissue mitochondria. A higher titer means there is a greater amount of AMA in the serum.

The AMA titers in PBC are almost universally greater than or equal to 1 to 40. This means that a serum sample diluted with 40 times its original volume still contains enough antimitochondrial antibodies to be detected in the binding reaction. A positive AMA with a titer of at least 1:40 in an adult with an elevated alkaline phosphatase is highly specific for a diagnosis of PBC. The antigen recognized by AMA in patients with PBC is now known to be PDC-E2 and is also often referred to as the M2 antigen, as discussed earlier. So, newly developed tests for antibodies that bind to PDC-E2 are more specific and are now available to confirm the diagnosis of PBC.

It is noteworthy that approximately 20% of patients with AMA also have antinuclear (ANA) and/or anti-smooth muscle (SMA) autoantibodies in their blood. The ANA and SMA are more characteristically found in a disease called chronic autoimmune hepatitis. It turns out that patients who have persistently undetectable AMA but otherwise have clinical, laboratory, and liver biopsy evidence of PBC, all have either ANA or SMA. These patients have been referred to as having AMA-negative PBC, autoimmune cholangiopathy, or autoimmune cholangitis. The natural history, associated diseases, laboratory test abnormalities, and liver pathology are indistinguishable between the AMA-positive and AMA-negative patients. Thus, it seems inappropriate, for now at least, to classify this AMA-negative disease as different from PBC. Accordingly, this situation should be referred to as AMA-negative PBC. Rarely, some other patients appear to concurrently have features of both PBC and chronic autoimmune hepatitis. Such patients are said to have an overlap syndrome.