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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

Preclinical phase

The first phase is characterized by the presence of AMA at a titer of greater than or equal to 1:40 in an adult without any abnormality of liver blood tests or any symptoms of liver disease. This phase is referred to as preclinical because there is usually no reason for people in this phase of the disease to see a physician or have testing. Furthermore, since screening tests for AMA are not routinely performed, only small numbers of such people have been identified. So, people with an AMA without symptoms or abnormal liver blood tests have been identified only as the result of research studies of autoantibodies in apparently healthy people.

However, even with only the isolated positive AMA, these people do appear to have PBC. This conclusion is based on the presence of diagnostic or compatible features on a liver biopsy and subsequent findings or clinical events during long-term observation. Thus, more than 80% of these individuals with only a positive AMA ultimately develop cholestatic liver blood tests followed by the typical symptoms of PBC.

After discovery of an isolated positive AMA test, the time before development of cholestatic liver tests ranged from 11 months to 19 years. The median time (the time at which 50% of the people had developed cholestatic liver tests) was 5.6 years. During 11 to 24 years of observation starting in the preclinical phase of 29 patients, 5 died. However, none of the five died as a result of liver disease and the median age at death was 78.

Asymptomatic phase

This phase is characterized by a positive AMA and cholestatic liver blood tests in a person without symptoms of liver disease. The incidental discovery of an elevated alkaline phosphatase is what most commonly leads to the diagnosis of PBC in this phase. The elevated alkaline phosphatase is usually discovered after testing the blood routinely or for another clinical reason.

The results of three large studies indicate that 40% of these asymptomatic patients will develop symptoms of liver disease within the next 6 years. Over and above that, another 33% of patients will likely develop symptoms between 6 and 12 years. Longer follow up is not available, but this asymptomatic phase may persist indefinitely in a minority of patients with PBC.