Learn The BasicsThe exact cause of primary biliary cholangitis (PBC) is not known, but it is thought that it is an autoimmune disease, in which the immune system mistakenly turns to the body’s own healthy tissues. It is thought that a combination of genetic and environmental risk factors leads to the development of PBC.
What causes PBC?
PBC is caused by the immune system mistakenly attacking the bile ducts in the liver. This immune system attack damages the bile ducts and leads to cholestasis or a decrease in bile flow. This, in turn, causes bile acids to build up inside the liver and leads to symptoms such as the skin and the white part of the eyes becoming yellow, dark urine, light and smelly stools and severe skin itching.
As the disease progresses, cholestasis leads to liver fibrosis, and in the late stages of the disease, cirrhosis and liver failure may occur.
An exact genetic cause of the disease has not been established, but several human leukocyte antigen (HLA) alleles are thought to be associated with PBC, with some increasing the risk of developing the disease and others being protective against it. These HLA alleles are DRB1, DR3, DPB1, DQA1 and DQB1.
Genetic risk factors
PBC affects primarily women who are 30 and 60 years old, though others can also be diagnosed with the disease.
Some people have a genetic predisposition to developing the disease. This is based on the fact that the disease is highly prevalent among first-degree relatives. Women whose mother has or has had PBC seem to be at a particularly high risk of developing PBC. However, the cause of this is not known. Twins are also more likely to develop PBC if their other twin also has the disease.
Even though PBC can affect people of all ethnicities, people of northern European descent may be at a higher risk of developing the disease, suggesting another genetic association.
Environmental risk factors
Environmental risk factors associated with PBC include exposure to toxic waste, smoking and cosmetic products such as nail polish and hair dye.
Infections such as urinary tract infections and bacteria such as Escherichia coli, Mycobacterium gordonae and Novosphingobium aromaticivorans have also been associated with PBC. Reproductive hormone replacement therapy may also be associated with an increased risk of PBC.
Prevention
Maintaining a healthy lifestyle can help prevent the development of PBC, even if you may have a genetic predisposition. This includes not smoking, not regularly drinking more than 14 units of alcohol in a week (one unit of alcohol roughly corresponds to a single serving of liquor, a small beer or a small glass of wine), and maintaining a healthy weight.
Risk of recurrence
The rate of PBC recurrence following a liver transplant can be as high as 35% in some patients and may happen three to five and a half years following the transplant.
Research has identified tacrolimus use for immunosuppression following a liver transplant as a risk factor for the recurrence of PBC following the transplant.
Reviewed by Harshi Dhingra, M.D., on December 14, 2023.
