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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 - Diagnosis
• Patient Comments: Primary Biliary Cirrhosis - Symptoms
• Find a local Gastroenterologist in your town
• Primary Biliary Cirrhosis Index

What are antimitochondrial antibodies (AMA)?

Between 95 and 98% of patients with PBC have autoantibodies in their blood that react with the inner lining of mitochondria. These autoantibodies are called antimitochondrial antibodies (AMA). Mitochondria are the energy factories present inside all of our cells, not just the cells of the liver or bile ducts. The mitochondria use the oxygen carried in the blood from the lungs as a fuel to generate energy. AMA bind to protein antigens that are contained in multienzyme complexes (packages of enzymes) within the inner lining of the mitochondria. The multienzyme complexes produce key chemical reactions necessary for life. These complexes are referred to as multienzyme because they are made up of multiple enzyme units.

AMA specifically react against a component of this multienzyme complex called E2. In PBC, AMA preferentially react with the E2 component of one of the multienzymes that is called the pyruvate dehydrogenase complex (PDC). Accordingly, the antigen is designated as PDC-E2. The practical importance of all of this is that the PDC-E2 antigen is now used, as will be discussed below, in a diagnostic test for detection of AMA. The PDC-E2 antigen is also referred to as M2, a term introduced to designate it as the second mitochondrial antigen discovered by researchers interested in PBC.

Do the AMA react with the bile ducts?

In as much as the bile ducts are the main targets of destruction in PBC, the question was asked whether the AMA reacts with the epithelial cell lining of the bile ducts. So, investigators prepared antibodies to PDC-E2. As expected, they found that these antibodies bound to the mitochondria within cells. But, sure enough, recent information suggests that these AMA autoantibodies also bind to PDC-E2 that lies outside the mitochondria yet within the epithelial cells lining the bile ducts. Indeed, these cells are the main targets of destruction in PBC.

This accumulation of PDC-E2 within the biliary epithelial cells is observed exclusively in the livers of patients with PBC, and not in normal livers or in livers from patients with any other types of liver disease. Interestingly, it was also observed in the livers of those two to five percent of PBC patients who do not have AMA in their blood (AMA-negative PBC). Furthermore, intense binding of these antibodies to biliary epithelial cells was also found to be the earliest indication of recurrence of PBC in a transplanted liver. (PBC is sometimes treated by liver transplantation, which will be discussed later.)

These observations led to a speculation that the antibodies were actually reacting with an antigen from an infectious agent. The idea was that the infectious agent was present in the biliary epithelial cells of patients with PBC and that the agent could also infect the biliary cells of a transplanted liver. (See the section below on the role of infection).