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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

Ultrasound imaging of the liver is recommended for patients whose blood tests show cholestasis. Cholestatic blood tests feature a disproportionately elevated alkaline phosphatase and ggt, compared to the ALT and AST. The purpose of the ultrasound exam is to visualize the bile ducts to exclude mechanical blockage (obstruction) of larger bile ducts as the cause of the cholestasis. Gallstones or tumors, for example, may cause mechanical obstruction of bile ducts. The blockage can cause increased pressure in the bile ducts that leads to dilation (widening) of the upstream bile ducts.

Dilated bile ducts caused by mechanical obstruction can usually be visualized on the ultrasonogram. The dilated bile ducts can also be seen using other imaging techniques such as computerized tomographic (CT) scanning, Magnetic Resonance Imaging (MRI), or an endoscopic procedure called ERCP. On the other hand, in PBC, the ducts that are being destroyed are so small that any dilation of upstream ducts cannot be seen with any of the imaging techniques. For the diagnosis of PBC in patients with cholestatic liver tests, a positive AMA and a normal ultrasound examination usually is sufficient. In this situation, other imaging studies of the bile ducts are usually not required.

The benefits of doing a liver biopsy (taking a tissue sample) include:

• Confirmation of the diagnosis
• Determination of the stage of disease
• Identification of any other concurrent liver disease

Pathologists (physicians who analyze tissue samples) have divided the evolution of PBC into four stages recognizable by the microscopic appearance of the liver biopsy.

1. Progressive inflammation of the portal tracts and their small bile ducts
2. The inflammation causes destruction of the small bile ducts and spreads to also involve the nearby liver cells (hepatocytes)
3. Extensive scars (fibrosis) protrude from the inflamed portal tracts into the region of liver cells
4. Cirrhosis

From a practical perspective, physicians most often divide the disease into prefibrotic (before scarring) and fibrotic (scarring or cirrhosis) stages, still usually using the biopsy findings.

Patients often ask if a liver biopsy is mandatory. The answer usually depends on the level of confidence in establishing the diagnosis of PBC using the liver tests, autoantibodies, and ultrasound. In the presence of cholestatic liver tests, high levels of AMA, and an ultrasound showing no bile duct obstruction in a middle-aged woman, the diagnosis of PBC can be made rather confidently without a biopsy. Treatment then can often be started, for example, with ursodeoxycholic acid (UDCA, a naturally occurring bile acid that is produced in small quantities by normal liver cells).

Without a biopsy, however, the stage (extent) of the disease would remain undefined. A biopsy helps the patient know where they are in the natural history of the disease. Furthermore, knowing the stage of PBC can help physicians decide about prescribing certain medications (for example corticosteroids) that may be effective in the early stages and less valuable in later stages.

On the other hand, PBC patients who already have the complications of cirrhosis (for example, ascites, varices, or hepatic encephalopathy) are presumed to have advanced liver disease. In these PBC patients the imaging studies alone are usually sufficient to exclude dilated ducts and a biopsy is not needed for staging the disease. Otherwise, the presence or absence of other symptoms (apart from the presence of those clearly due to the complications of cirrhosis) is not an accurate guide to the stage of PBC on a liver biopsy. For example, in one large series of patients, approximately 40% of those without symptoms had cirrhosis on liver biopsy.