Primary biliary cholangitis (PBC) is a chronic progressive liver disorder that primarily affects females and typically becomes apparent during middle age. Obstruction of the small bile ducts is accompanied by yellow discoloration of the skin (jaundice). Excessive amounts of copper accumulate in the liver, and fibrous or granular hardening (induration) of the soft liver tissue develops. The course of primary biliary cholangitis is divided into four progressive stages. Although the exact cause of primary biliary cholangitis is unknown, possible immunological, autoimmune, genetic, and/or environmental factors are under investigation as potential causes of the disorder.
Primary biliary cholangitis is characterized initially by blockage, then deterioration and loss of the small bile ducts inside the liver. This results in the abnormal retention (cholestasis) of bile acids, bilirubin, copper, and other substances that are normally excreted into bile. These substances cause further damage to liver cells. Itching often results from the abnormal passage of these substances into the blood, skin, and other soft tissues of the body. Excessive amounts of fat soluble substances (lipids) and cholesterol are found circulating in the blood. Yellow nodules or plaques form on the skin and possibly in internal organs.
The bile acid concentration in the intestines is inadequate for complete digestion and absorption of fats (triglycerides) in the diet. Additionally, normal absorption of vitamins A, D, E, and K as well as calcium may be diminished, and iron deficiency anemia may develop. Loss of bone density (osteoporosis) and bone softening (osteomalacia) occurs in approximately 25 percent of affected individuals.
As the disorder progresses other very serious problems may present themselves. Among these serious problems are:
Increased pressure in the major vein (portal vein) of the liver (portal hypertension;
Enlarged veins other than the portal vein (varices);
Osteoporosis or weakened bones due to the interference with the metabolism of vitamin D and calcium;
Vitamin deficiencies appear because the lack of bile interferes with the metabolism of the fat soluble vitamins A, D, E, and K.
Other complications, often reflecting the disturbance of the immune system, are not uncommon. These include:
CREST syndrome which is a serious immune system disorder leading to the thickening of connective tissues in the body.
Raynaud’s phenomenon is part of the CREST syndrome that presents as small capillary spasms and damaged circulation in the face of stresses such as emotional upsets and cold Rheumatoid arthritis is another immune disorder that may present as PBC progresses.
An inflammatory bowel disease called ulcerative colitis may also be part of the complications related to PBC.
The exact cause of primary biliary cholangitis (PBC) is unknown. Possible immunological, autoimmune, genetic, and/or environmental factors are under investigation as potential causes of the disorder.
According to many researchers, immunological abnormalities may be an important contributing factor in the development of PBC. The immune system is divided into several components, the combined actions of which are responsible for defending against different infectious agents (i.e., invading microscopic life-forms [microorganisms]). The T cell system (cell-mediated immune response) is responsible for fighting yeast and fungi, several viruses, and some bacteria. The B cell system (humoral immune response) fights infection caused by other viruses and bacteria. It does so by secreting immune factors called antibodies (also known as immunoglobulins) into the fluid portion of the blood (serum) and body secretions (e.g., saliva). Researchers have found that individuals with primary biliary cholangitis have unusually decreased numbers of circulating T cells in the blood and abnormalities in T cell function and regulation (i.e., helper and suppressor T cells). The role of T cell abnormalities in potentially contributing to the symptoms associated with PBC is not yet known.
In addition, many researchers indicate that autoimmune factors may play a contributing role in causing primary biliary cholangitis. Autoimmune disorders are caused when the body’s natural defenses against invading microorganisms mistakenly attack healthy tissue. For example, antibodies typically directly kill “invaders” (e.g., microorganisms, toxins, and other foreign substances) or coat them so they are more easily destroyed by white blood cells. (The white blood cells [leukocytes] are part of the body’s system of defenses, playing an essential role in protecting against infection as well as fighting infection once it occurs.) However, in some cases, antibodies may improperly form against certain of the body’s own tissues, causing autoimmune disease.
In the case of primary biliary cholangitis, studies have demonstrated that approximately 95 percent of affected individuals produce antibodies (known as “autoantibodies”) that act upon certain of the body’s own mitochondria (mitochondrial autoantigens, e.g., E2 component of pyruvate dehydrogenase complex [PDC-E2], E2 component of branched chain 2-oxo-acid dehydrogenase complex [BCOADC-E2]). Mitochondria are found by the hundreds within cells in the body and carry the blueprints for making energy. They have their own genetic instructions (mtDNA) and are located outside of the nucleus of the cell (cytoplasm). The role of antimitochondrial antibodies in potentially causing the symptoms associated with primary biliary cholangitis is not clearly understood.
In addition, in some individuals with PBC, specialized laboratory tests conducted on the fluid portion of the blood (serum) have revealed the presence of certain antibodies typically produced in response to certain viruses (i.e., retroviral antigens). Antigens are those substances, such as microorganisms, toxins, or other foreign substances, that may trigger production of particular antibodies as part of an immune response. According to the medical literature, such findings may suggest that, in individuals with primary biliary cholangitis, certain antibodies may be mistakenly reacting to one or more of the body’s own proteins that are very similar to protein fragments from certain invading viruses (i.e., the immune system is unable to distinguish between the “mimic” protein on the surface of certain viruses and the body’s own proteins). On the other hand, such findings may provide evidence that PBC may be due, at least in part, to an underlying viral infection, a finding that has been demonstrated in other autoimmune disorders.
Because a number of familial cases of primary biliary cholangitis have been reported in the medical literature, it is also suspected that certain genetic factors may play some role in the development of PBC. Some researchers suggest that, in such cases, environmental or other factors may trigger symptoms in those with a genetic predisposition to the disorder.
Further studies are needed to determine the potential role(s) that immunological, autoimmune, genetic, environmental, and/or other factors may play in causing primary biliary cholangitis.
Primary biliary cholangitis primarily affects females. The disorder typically becomes apparent during middle age, initially affecting most individuals between the ages of 30 to 65 years. However, according to reports in the medical literature, the disorder has been diagnosed in females as young as approximately 22 years of age and in elderly females in their early 90s. It has been estimated that primary biliary cholangitis affects from approximately four to 15 of every one million individuals annually. Many familial cases of primary biliary cholangitis have been reported in the medical literature.
Treatment of primary biliary cholangitis is often directed at symptoms. The drug cholestyramine relieves itching in almost all affected individuals. Colestipol hydrochloride may also be effective against itching. Large-volume plasmapheresis may relieve itching in those who do not respond to drug treatment. This procedure is a method for removing unwanted substances (toxins, metabolic substances, and plasma parts) from the blood. Blood is removed from the affected individual and blood cells are separated from plasma. The individual’s plasma is then replaced with other human plasma and the blood is re-transfused into the affected individual.
Malabsorption of fat-soluble vitamins may be treated with vitamin K 1, A, D, and calcium supplementation. Iron deficiency anemia responds to oral iron supplements. Additional folic acid is recommended for individuals taking cholestyramine because this drug can cause a folic acid deficiency. Folic acid and cholestyramine should be taken several hours apart since they may react and prevent folic acid absorption when taken together. Loss of fat in the stools (steatorrhea) may be treated by a low-fat diet supplemented with medium-chain triglycerides to maintain high caloric intake.
The drug ursodiol (Urso), also known as ursodeoxycholic acid, has been approved by the Food and Drug Administration (FDA) for the treatment of primary biliary cholangitis. Ursodiol is manufactured by Axan Pharma and Schwarz Pharma US.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
For information about clinical trials sponsored by private sources, contact:
For more information about clinical trials conducted in Europe, contact: https://www.clinicaltrialsregister.eu/
Beers MH, Porter RS, Jones TV, Kaplan JL, Berkwits M. eds. The Merck Manual, 18th ed. Whitehouse Station, NJ: Merck Research Laboratories; 2006:218-19.
Berkow R., ed. The Merck Manual-Home Edition.2nd ed. Whitehouse Station, NJ: Merck Research Laboratories; 2003:799-800.
Kasper, DL, Fauci AS, Longo DL, et al. Eds. Harrison’s Principles of Internal Medicine. 16th ed. McGraw-Hill Companies. New York, NY; 2005:1860-61.
Yamada T, Alpers DH, Kaplowitz N, Laine L, et al. Eds. Textbook for Gastroenterology. 4th ed. Lippincott Williams & Wilkins. Philadelphia, PA; 2003:2374-85.
O’Leary JG, Pratt DS. Cholestasis and cholestatic syndromes. Curr Opin Gastroenterol. 2007;23:232-6.
Lazaridis KN, Talwalkar JA. Clinical epidemiology of primary biliary cirrhosis: incidence, prevalence, and impact of therapy. J Clin Gastroenterol. 2007;41:494-500.
He XS, Ansari AA, Ridgway WM, Coppel RL, Gershwin ME. New insights to the immunopathology and autoimmune responses in primary biliary cirrhosis. Cell Immunol. 2006 Jan;239(1):1-13.
Leung PS, Coppel RL, Gershwin ME. Etiology of primary biliary cirrhosis: the search for the culprit. Semin Liver Dis. 2005;25:327-36.
McKusick VA, Ed. Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Biliary Cirrhosis, Primary; PBC. Entry Number; 109720: Last Edit Date; 04/02/2014. http://omim.org/entry/109720 Accessed April 14, 2016.
The information in NORD’s Rare Disease Database is for educational purposes only and is not intended to replace the advice of a physician or other qualified medical professional.
The content of the website and databases of the National Organization for Rare Disorders (NORD) is copyrighted and may not be reproduced, copied, downloaded or disseminated, in any way, for any commercial or public purpose, without prior written authorization and approval from NORD. Individuals may print one hard copy of an individual disease for personal use, provided that content is unmodified and includes NORD’s copyright.
National Organization for Rare Disorders (NORD)
55 Kenosia Ave., Danbury CT 06810 • (203)744-0100