All diseases are different. Some are immediately apparent, like a heart attack. Some have the gall to hide undetected for years. This might sound nice, but the damage that can be done while undetected gets worse over time. Primary Biliary [billy-ur-ee] Cholangitis [kow-luhn-jai-tuhs] (PBC) destroys our bile ducts, often without our knowledge until other parts of the body are damaged.

PBC is a somewhat rare disease, affecting 1 in every 3-4 thousand people, so around 100,000 Americans. Of these, around 90% of cases are in women. Most patients with PBC are diagnosed in their 50’s and 60’s, though the disease may start as young as 30. On its own, PBC may not have many symptoms, but leads to debilitating conditions of the liver such as cirrhosis, failure, and cancer. It also causes downstream damage across the body such as metabolic bone disease and malabsorption of nutrients.

So what is Primary Biliary Cholangitis? There are clues in the name. The biliary system carries bile, a digestive fluid produced in the liver and sent to the gallbladder and intestines. Chol- also means bile, ang- means vessel, and -itis means inflamed. Cholangitis means the tubes that carry bile from the liver (called bile ducts) are inflamed. This disease is termed “primary” because it is the direct cause of inflammation and damage. A “secondary” disease is one caused by previous infection or disease; bile ducts can also be damaged by chemotherapy or surgical trauma to the lower bile system, for example. Altogether, primary biliary cholangitis is a disease that directly causes inflammation and damage to bile ducts.

There are many bile ducts and many kinds of bile ducts, with the smallest being ultra-fine and located throughout the liver. These collect digestive fluid and transport them to ever bigger ducts to be stored in the gallbladder and sent to the digestive tract. In PBC, these small ducts are destroyed. A good rule of thumb is that when digestive fluid isn’t going to the digestive tract there may be problems. The buildup of bile damages the liver over time. Bile is critical for digesting fats and many vitamins. When bile fails to be de-livered to the digestive tract we may suffer malnutrition and fatigue.

Most PBC patients are symptom-free but several experience debilitating symptoms, especially at later stages. Major symptoms are fatigue and itching (called pruritus). Jaundice, skin pigmentation, and fat buildup under the skin are other potential problems. Since so many people have no symptoms, or vague ones that can be attributed to other things, PBC is detected by looking at the blood.  The primary evidence is the presence of antimitochondrial antibodies. These are immune system proteins that target mitochondria, the powerhouse of the cell.

Increased antimitochondrial antibodies give us a good clue as to the true nature of primary biliary cholangitis. PBC is an autoimmune disorder – our immune system attacking healthy cells in the body. The cells at hand are the ones that make up the bile ducts. How this happens is complicated, and not fully known. We do know that there is a strong genetic component. X marks the spot in this case; since it affects mostly women, the X chromosome is a good candidate for where the trouble lies. The genetics aren’t enough, however.

PBC requires an environmental component. Environmental in this case means anything that started outside of our own bodies and got in. Environmental risks include things that aren’t alive, like nail polish, hair dye, cigarettes, and toxic waste. Here at ENCORE Research Group we recommend avoiding toxic waste sites whenever possible. Living environmental factors include bacteria that degrade the immune system. This is a slow process. The bile duct cells become affected and some die. As they die they present parts of their mitochondria to the immune system, which learns to attack them. Eventually, the immune system starts attacking bile duct cells directly, causing scarring and cell death. This causes the eventual collapse of the small bile ducts.

So what can be done? We can’t fight the underlying autoimmune disease yet. Current treatments are aimed at restoring the function of bile. The major medication is ursodeoxycholic [er-sudi-oxy-cholic] acid (UDCA), as synthetic bile acid. This only helps 60% of the time, and may be supplemented with obeticholic [oh-bet-i-colic] acid (OCA) to aid in the process. Neither of these help with symptoms. Itching may be treated with creams and cold water, and fatigue is treated with exercise, occupational, and physical therapy. Sicca, meaning dry eyes and mouth, is also a symptom, and is treated with artificial tears and saliva, or medications that increase these. Future treatments would target the underlying immune response or the associated inflammation. Either way, a treatment that stops damage is needed to help sufferers of PBC – and to keep those that aren’t suffering feeling well!

Written By Benton Lowey-Ball, BS Behavioral Neuroscience

Sources:

Dauphinee, J. A., & Sinclair, J. C. (1949). Primary biliary cirrhosis. Canadian Medical Association Journal, 61(1), 1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1591584/?page=1

Lleo, A., Invernizzi, P., Mackay, I. R., Prince, H., Zhong, R. Q., & Gershwin, M. E. (2008). Etiopathogenesis of primary biliary cirrhosis. World journal of gastroenterology: WJG, 14(21), 3328.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2716587/

Onofrio, F. Q., Hirschfield, G. M., & Gulamhusein, A. F. (2019). A practical review of primary biliary cholangitis for the gastroenterologist. Gastroenterology & hepatology, 15(3), 145. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6495411/

Ruemmele, P., Hofstaedter, F., & Gelbmann, C. M. (2009). Secondary sclerosing cholangitis. Nature Reviews Gastroenterology & Hepatology, 6(5), 287-295. https://www.nature.com/articles/nrgastro.2009.46

Strazzabosco, M., & Fabris, L. (2008). Functional anatomy of normal bile ducts. The Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology: Advances in Integrative Anatomy and Evolutionary Biology, 291(6), 653-660.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3743051/