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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 causes destruction of the bile ducts in PBC?

AMA are tremendously important as a diagnostic marker in patients with PBC. Despite that, no evidence exists that the AMA itself causes the destruction of the biliary epithelial cells lining the small bile ducts. Neither the presence nor the amount (titer) of AMA in the blood appears to be related to the inflammatory destruction of the bile ducts. Indeed, immunization of animals with PDC-E2 antigen results in production of AMA without any liver or bile duct damage (pathology).

What, then, causes the destruction of the bile ducts in PBC? Inspection of liver biopsies from patients with PBC indicates that T-lymphocytes surround and invade the small bile ducts. Thus, T-lymphocytes appear to be responsible for the death of the biliary epithelial cells lining the ducts and the destruction of the bile ducts. T-lymphocytes capable of directly killing target-cells (for example, biliary epithelial cells) are called cytotoxic T-lymphocytes, meaning that these T-cells are toxic to the target cells. And, in fact, cytotoxic T-lymphocytes have been observed in liver biopsies to invade the bile ducts and to be present in areas where biliary epithelial cells are dying.

Other T-lymphocytes that surround the bile ducts are known to produce chemicals that can also cause biliary epithelial cells to die. Some of these chemicals actually stimulate the biliary epithelial cells themselves to secrete small proteins that attract more T-lymphocytes. Paradoxically, then, this response by the biliary epithelial cells might result in even greater injury to the bile ducts, in sort of a vicious cycle.

Recent studies of T-lymphocytes isolated from the inflamed livers of patients with PBC have shown that these T-lymphocytes can, in fact, kill biliary epithelial cells. Moreover, many of the T-lymphocytes recognized the digested fragments of PDC-E2. These observations suggest the possibility (hypothesis) that the T-lymphocytes might attack the biliary epithelial cells because these cells display PDC-E2 antigens in their HLA (Human Lymphocyte Antigen) molecules to which the T lymphocytes react. No direct evidence, however, supports this hypothesis. The fact is that the actual antigens on biliary epithelial cells that are recognized by invading, destructive T-lymphocytes remain to be determined. However, the biliary epithelial cells do contain molecules, such as intercellular adhesion molecule-1, that are required for activated T lymphocytes to adhere to the cells that they kill.