Causes of cholangitis

Last updated Nov. 25, 2024, by Marisa Wexler, MS
Fact-checked by Marta Figueiredo, PhD

Cholangitis is a liver disease marked by inflammation in the bile ducts. These are a series of tubes that carry bile, a digestive fluid, from the liver to the gallbladder — an organ that stores bile until it’s needed for digestion — and then to the digestive system.

Bile duct inflammation can interrupt the normal flow of bile and cause damage throughout the biliary system, namely the bile ducts, liver, and gallbladder. This can lead to cholangitis symptoms such as abdominal pain and jaundice (yellowing of the skin and eyes). Built-up bile can also leak out into the bloodstream, causing itching.

There are two main types of cholangitis, acute and chronic, and the causes of cholangitis are distinct in each. Acute cholangitis develops quickly and is most frequently associated with a bacterial infection in the bile ducts. By contrast, chronic cholangitis develops slowly over time, usually as a result of an autoimmune disease.

Both forms of cholangitis can lead to life-threatening complications if not managed properly. Identifying cholangitis causes is key to obtaining an accurate diagnosis and ensuring patients receive proper and timely treatment.

Causes of acute cholangitis

Acute cholangitis, also known as ascending cholangitis, is a form of cholangitis where symptoms develop suddenly. Most cases are the result of a bacterial infection in the bile ducts. This triggers an inflammatory response from the immune system that aims to fight off the infection, ultimately giving rise to cholangitis.

Acute cholangitis can lead to symptoms such as fever, jaundice, itching, and abdominal pain. In severe cases, patients may experience cognitive changes, low blood pressure, or sepsis, where an infection spreads through the bloodstream and organs start to shut down.

In virtually all cases, acute cholangitis is associated with a biliary obstruction — or a blockage in the bile ducts — which causes bile to build up in the biliary system and creates a fertile breeding ground for infectious bacteria.

This biliary obstruction is most commonly caused by gallstones trapped in the common bile duct, the longest bile duct. Gallstones are hardened deposits of bile materials that can form in the gallbladder and travel into bile ducts. When gallstones become trapped in a bile duct they are called bile duct stones.

Other causes of ascending cholangitis that are similarly associated with biliary obstruction include:

• biliary strictures, or abnormal narrowing of bile ducts due to surgery, trauma, or certain tumors
• parasites, such as roundworms and tapeworms, in the biliary system.

Causes of chronic cholangitis

Chronic cholangitis, in turn, is a slowly developing condition that typically does not cause symptoms until it has already progressed to cause organ damage.

Chronic forms are most commonly the result of an autoimmune disease in which the body’s immune system drives abnormal immune attacks against healthy cells in or around the bile ducts. This causes chronic inflammation that can make bile ducts hard and narrow, or sclerotic, which can result in biliary strictures, slowed or stalled bile flow (cholestasis), and bile accumulation in the liver, damaging the organ.

Autoimmune diseases that most frequently cause chronic cholangitis include:

• primary biliary cholangitis, or PBC
• primary sclerosing cholangitis, or PSC
• IgG4-associated cholangitis.

In PBC, the immune system targets only the bile ducts within the liver, while PSC can affect the ducts inside and outside the organ. Both of these rare diseases show different frequencies across sexes, with PBC being 10 times more common among women, and PSC affecting twice as many men as women.

IgG4-associated cholangitis is a major manifestation of IgG4-related disease. This is a rare autoimmune disease that causes inflammation in several organs and mainly affects men in their 60s and 70s.

As with most autoimmune disorders, the underlying mechanisms of PBC, PSC, and IgG4-associated cholangitis are not fully understood. However, all are thought to arise due to a combination of genetic and environmental factors. Scientists have identified several genetic mutations that seem to increase the risk of developing PBC, PSC, and IgG4-associated cholangitis. In terms of environmental factors, exposure to chemicals and toxins, and certain infections have been associated with these diseases.

Chronic forms of cholangitis associated with autoimmune disease also tend to co-occur with other autoimmune and inflammatory disorders. In particular, there’s a strong link between PSC and inflammatory bowel disease (IBD), a group of autoimmune diseases characterized by inflammation in the intestines.

Still, chronic cholangitis can also occur independently of autoimmune diseases. One of such forms is secondary sclerosing cholangitis, which can be caused by many different factors and conditions, including:

• chronic biliary obstruction
• inherited disorders that affect the bile ducts, including cystic fibrosis and Caroli disease
• surgical trauma to the bile ducts
• repeated episodes of bacterial cholangitis
• exposure to toxins
• radiation therapy.

Risk factors

Because acute cholangitis causes are different from chronic cholangitis causes, risk factors differ between these forms. With acute cholangitis, the main risk factors are obstructions in the biliary system and potential exposures to bacterial infection. In contrast, the main risk factors of chronic cholangitis are autoimmune diseases and other underlying health issues.

Obstructions

Biliary obstructions are a major risk factor for acute cholangitis. When the biliary system is obstructed, bile cannot flow properly and it builds up. This creates a fertile breeding ground for infectious bacteria that can cause acute cholangitis.

Some types of obstructions that may set the stage for acute cholangitis include:

• gallstones or blood clots that block the common bile duct
• cancers or growths in or around the biliary system
• biliary strictures, which can occur due to developmental problems, cancers, or as a complication from surgeries or abdominal trauma
• swelling of other organs around the biliary system, especially the pancreas, which can put pressure on the bile ducts
• parasites in the biliary system, namely certain types of worms.

Consuming a high-fat diet, having a sedentary lifestyle, being obese, and experiencing rapid weight loss are known risk factors for gallstone formation, and may therefore also increase the risk of acute cholangitis. Moreover, heavy alcohol consumption may result in cirrhosis, or irreversible tissue scarring, which is another gallstone risk factor.

Infections

Another major risk factor of acute cholangitis is a bacterial infection in the bile ducts. Bacteria that most commonly cause acute cholangitis include Escherichia coli, Klebsiella, and Enterobacter — all common inhabitants of the human gut — as well as Pseudomonas and Citrobacter, two types of bacteria known to cause disease and to have high resistance to antibiotics.

When these bacteria grow in the bile ducts, they can damage biliary tissue, and the immune system will launch an offensive trying to fight off the infection, ultimately leading to bile duct inflammation.

Sometimes, bacteria can sneak into the bile ducts from other parts of the body, for example if there is backflow of bile from the small intestine. Bile duct infections can also occur due to the spread of blood infections, which can be detected by blood culture.

Medical tests to examine the liver or gallbladder are another common way that bacteria can get into the bile ducts. In some of those tests, doctors insert a thin tube, or an endoscope, into the biliary system, and it’s possible for infectious bacteria to piggyback into the bile ducts on the medical equipment.

Also, conditions that weaken the immune system such as infection with human immunodeficiency virus, or HIV, can make it harder for the body to fend off invading bacteria, which may increase the risk for infections that cause acute cholangitis or secondary sclerosing cholangitis.

Autoimmune factors

Autoimmune factors are the main risk factors of chronic cholangitis. The abnormal immune attacks in PBC, PSC, and IgG4-associated cholangitis target healthy cells in the bile ducts and cause longstanding inflammation. As bile duct cells die, they are replaced by scar tissue that can result in cirrhosis and, eventually, liver failure.

Increasing evidence shows that autoimmune diseases often occur simultaneously, suggesting shared underlying mechanisms. Some autoimmune conditions that have been linked to an increased risk of PBC and/or PSC include:

• inflammatory bowel disease, and particularly one of its types called ulcerative colitis
• celiac disease
• autoimmune thyroid disease
• type 1 diabetes
• systemic lupus erythematosus
• Sjögren’s disease
• systemic sclerosis
• rheumatoid arthritis.

Prevention and risk reduction

It’s not possible to completely prevent cholangitis in all situations, but certain steps can be taken to reduce the risk of developing cholangitis, and to minimize the risk of serious complications.

As biliary obstructions are a major risk factor for acute cholangitis, maintaining a healthy lifestyle may help to reduce the risk of obstructions due to gallstones, tumors, and parasites. These lifestyle changes may include eating well, consuming fewer fats, being physically active, maintaining a healthy weight, and avoiding toxic substances such as alcohol and tobacco.

Also, quick and effective management of potential obstructions is a key way to reduce risk. Prompt detection and removal of gallstones, which can be detected using an imaging technology called magnetic resonance cholangiopancreatography, is particularly important.

Preventive approaches may also include rapid and appropriate treatment for tumors or parasites in the biliary system or around it. In cases where bile ducts have become narrowed or pinched, it may be necessary to surgically place a stent to reopen the ducts and prevent cholangitis relapse.

As for chronic cholangitis, people with IBD and other underlying autoimmune conditions that may increase the risk of chronic cholangitis should undergo regular monitoring. Early detection is key to managing cholangitis timely and effectively and ensuring the best possible outcomes for patients.

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