Causes of PBC

The cause(s) of primary biliary cirrhosis are unknown. The word “primary” suggests the disease has a spontaneous onset. The term “biliary” indicates the intrahepatic bile ducts are affected. Cirrhosis is the end result of the disease once a person enters into the final stages. A liver transplant is the only known cure for the disease at this time. However, medication is offered to slow the progress of PBC.

The Role of the Immune System

While the causes for PBC remain unidentified, there are a number of theories pertaining to disease origin. Primary biliary cirrhosis is thought to be a disease that affects immune system functioning. Thus, PBC is considered an autoimmune disease. It is sometimes called “a loss of self tolerance.” The immune system's primary job is to protect the body and organs from germs, viruses, bacteria, and other foreign invaders. Instead, in the case where an autoimmune disease is present, the immune system begins attacking the body, organs, and healthy tissue.

While the causes for PBC remain unidentified, there are a number of theories pertaining to disease origin. Primary biliary cirrhosis is thought to be a disease that affects immune system functioning. Thus, PBC is considered an autoimmune disease. It is sometimes called “a loss of self tolerance.” The immune system's primary job is to protect the body and organs from germs, viruses, bacteria, and other foreign invaders. Instead, in the case where an autoimmune disease is present, the immune system begins attacking the body, organs, and healthy tissue.

According to the Cleveland Clinic in Ohio, it is believed the immune system causes destruction to biliary epithelial cells via “direct cytoxicity” (cellular toxification) and through “lymphokine-mediated cell damage,” all of which leads to the progression of PBC. Lymphokines call immune system responses into action, promote the activation and control the movement of cells, destroy targeted cells for destruction, and play a role in the immune system's inflammatory response. In people who have PBC, for reasons unknown, the immune system begins attacking the small bile ducts in the liver.

The immune system sends T-cells (cells that destroy bacteria and viruses) to the bile ducts. The T-cells are responsible for the slow destruction of the surface of the small bile ducts in the liver. The bile ducts are slowly scarred and the scar tissue disrupts the natural movement of bile. The bile begins to build up in the liver, and this, in turn, causes additional inflammation and scarring. The scarring process leads to fibrosis and eventual cirrhosis. 

The Role of Genetics & Environmental Factors 

It is believed genetics and environmental factors both play a role in the disease's onset. According to the National Digestive Diseases Information Clearinghouse (NDDIC), genetics play in PBC onset by making a person more likely to develop the autoimmune disease. People who have a sibling or parent with the condition are more likely to develop PBC, and this is particularly true in the case of identical twins. It is surmised in people who are genetically predisposed to developing primary biliary cirrhosis, certain environmental factors might trigger the disease or worsen the condition.

Some of the environmental factors suspected to have a role in triggering the onset of primary biliary cirrhosis include infections, exposure to toxins and chemicals, and smoking. According to NHS Choices, additional environmental factors are thought to have some connection with the onset of PBC, including urinary tract infections, hormone replacement therapy, cosmetics, nail varnish, and living near a location where toxic waste is dumped. The NHS cautions however, there are no proven triggers of primary biliary cirrhosis, and all of the latter mentioned triggers are causes in theory only.

An article entitled Common Bacteria Activating Natural Killer T Cells May Cause Autoimmune Liver Disease, on ScienceDaily online reveals a potential cause of primary biliary cirrhosis is a ubiquitous bacterium. Researchers from the Cincinnati Children's Hospital Medical Center injected mice with Novosphingobium aromaticivorans (N. aromaticivorans), which in turn, activated the killer T-cells triggering autoimmune reactions that induce liver disease (May, 2008). N. aromaticivorans, a pervasive bacterium responsible for activating environmental estrogens and metabolizing xenobiotics, plays a role in PBC development. Xenobiotics is a term derived from the Greek work xenos meaning “foreign” and bios meaning “life” – thus, xenobiotics are foreign substances in the body, whether the substances are organic compounds, medications, or pollutants. N. aromaticivorans is found in water and soil.

Dr Jochen Mattner, a researcher and physician from the Children's Hospital Medical Center's Division of Immunobiology at Cincinnati, also stresses that the findings in no way implicate N. aromaticivorans as a single cause for the disease, and there may be additional causes of primary biliary cirrhosis that remain unknown. However, the findings now provide researchers with a model that can help in further understanding autoimmunity and immunologic tolerance.