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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

What is the role of infection?

The possibility that PBC is caused by an infection with a virus, bacterium, or fungus has generated a number of studies. To date, none has shown conclusively that PBC is an infectious disease or even that it is triggered by a self-limited (nonpersistent) infection. Clearly, PBC is not associated with infection by any of the known hepatitis viruses. Furthermore, none of the new viruses that may cause liver diseases have been found preferentially or exclusively in patients with PBC.

Investigators are currently pursuing leads suggesting that the biliary epithelial cells of patients with PBC may contain an infectious virus that belongs to the class of viruses called retroviruses. (The human immunodeficiency virus, HIV, is an example of a retrovirus.) These studies have identified genetic fragments of a retrovirus in the biliary epithelial cells of patients with PBC. Nevertheless, further research is required to answer the important question of whether PBC is caused by a retroviral infection.

The possibility that PBC is caused by infection with bacteria has intrigued clinical investigators for decades. You see, the mitochondria in the cells of mammals were derived, during evolution, from bacteria. Thus, many bacteria contain antigens that react with the AMA found in patients with PBC. Some of these bacteria have been cultured from the urine of patients with PBC who have recurrent urinary tract infections. Interestingly enough, as discussed later, recurrent urinary tract infection has been recognized as a risk factor for developing PBC.

This association between urinary tract infection and PBC led to the speculation that a bacterial infection might trigger an immune response that developed into an autoimmune reaction. Although this speculation is plausible, there is currently no direct evidence that this sequence of events occurs in PBC. As a matter of fact, molecular techniques now exist to screen livers for the presence of any type of bacteria. So far, these kinds of studies have found no evidence of a chronic bacterial infection in PBC.

Another intriguing possibility is that an infection with a virus, bacterium, fungus or parasite might introduce foreign proteins that mimic the protein antigens of mitochondria. An immune response against these foreign proteins could develop antibodies and T lymphocytes that react with the mimicked self-proteins, thereby resulting in autoimmunity. In other words, the body's immune system responds to the foreign proteins but it reacts against its own mitochondrial proteins. This phenomenon is called molecular mimicry.

One of the best examples of molecular mimicry is found in rheumatic fever. This condition is an autoimmune reaction involving the skin, joints, and heart muscle, that is caused by an immune response to a streptococcal bacterial infection. Now, rheumatic fever is usually diagnosed within a few weeks of having strep throat. Physicians, therefore, recognized the relationship between the two events (streptococcal infection and rheumatic fever) before molecular mimicry was understood. PBC, however, is usually a more subtle condition that might not be diagnosed for many years. Therefore, if a transient infection were to trigger molecular mimicry in PBC, causing an autoimmune reaction, the relationship between the infection and the autoimmune disease might be easily missed.