Cholestasis causes

Last updated April 14, 2025, by Lindsey Shapiro, PhD
Fact-checked by Marta Figueiredo, PhD

Cholestasis, a liver condition in which the flow of the digestive fluid bile is slowed or stalled, can have a number of possible causes, including diseases affecting the liver or neighboring tissues and organs, bacterial infections, physical blockages, certain medications, and pregnancy.

Bile is made in the liver and carried through a series of tubes called the bile ducts to the gallbladder, where it is stored, and the small intestine, where it is used to aid digestion. The bile ducts also pass through the pancreas, where certain digestive enzymes are made.

The symptoms of cholestasis generally arise because bile accumulates toxically in the liver and leaks into the bloodstream instead of making its way to the digestive tract.

Cholestasis can be classified as intrahepatic, when it occurs within the liver, or extrahepatic, where bile flow outside the liver is impacted. Cholestasis causes typically differ between these two forms.

Knowing exactly what causes cholestasis in each individual is essential for doctors to make the appropriate treatment choices. For that reason, determining the cause is generally a key part of the diagnostic process.

Intrahepatic cholestasis causes

There are multiple intrahepatic cholestasis causes, including liver diseases, infections, certain medications, and pregnancy.

Chronic liver diseases lead to inflammation, scarring, and damage to the organ. Many can eventually lead to cirrhosis, a complication where the organ becomes permanently scarred and damaged. Such damage can cause harm to hepatocytes — the liver cells that produce bile — or narrowing of the bile ducts in the liver, ultimately driving intrahepatic cholestasis. Liver diseases that may cause intrahepatic cholestasis include:

alcohol-related liver disease, which causes liver damage due to the liver’s inability to metabolize high amounts of alcohol
acute or chronic forms of hepatitis, or liver inflammation, that are most commonly caused by viral infections
liver cancer or other cancers that have spread to the liver
progressive familial intrahepatic cholestasis, a rare genetic condition where bile secretion from liver cells is impaired
intrahepatic biliary atresia, a rare liver disease in infants in which the bile ducts inside the liver are blocked or absent
primary biliary cholangitis (PBC), a rare autoimmune disease that causes chronic bile duct inflammation, or cholangitis, particularly in the ducts within the liver
primary sclerosing cholangitis (PSC), another rare condition marked by chronic cholangitis in which autoimmune responses affect the bile ducts inside and outside the liver.

Some whole-body, or systemic, conditions that can affect the liver may also lead to intrahepatic cholestasis, including:

Alagille syndrome, a rare genetic condition that affects many organs and tissues, including the liver, which typically has fewer-than-normal bile ducts
amyloidosis, a disease marked by the accumulation of toxic protein deposits that can affect the liver and intrahepatic bile ducts, disrupting bile production or flow
lymphoma, a type of blood cancer, which can directly infiltrate the liver and cause damage to the intrahepatic bile ducts or cause enlarged lymph nodes that compress these ducts
sarcoidosis, where small clumps of immune cells build up in the body and can cause inflammation that damages the intrahepatic bile ducts.

Most medications and substances are processed in the liver. Some can be harder for the liver to metabolize, damaging liver cells and leading to a form of intrahepatic cholestasis called drug-induced cholestasis. Potentially offending medications include:

antibiotics, including ampicillin, penicillin, and amoxicillin
anabolic steroids, which are derivatives of the male sex hormone testosterone that are used as hormone replacement therapies and for treating certain conditions
estrogen-containing medications such as birth control pills and hormone replacement therapies, or estrogen receptor modulators such as tamoxifen (sold as Soltamox and others)
certain antipsychotic medications, including chlorpromazine and prochlorperazine (sold as Procomp and others)
the antidepressant imipramine
cimetidine (sold as Tagamet HB and others), used to treat stomach ulcers
the antifungal terbinafine (sold as Lamisil and others)
certain chemotherapy agents.

Other possible intrahepatic cholestasis causes include:

tuberculosis, bacterial infections that cause abscesses in the liver, or serious infections that have spread to the bloodstream (sepsis), all of which can drive inflammation that blocks or damages the bile ducts
total parenteral nutrition, or being fed exclusively through a vein, which bypasses the digestive tract and can disrupt normal signals that promote bile flow
hormonal changes in pregnancy that affect bile flow.

Intrahepatic cholestasis of pregnancy causes

Intrahepatic cholestasis of pregnancy (ICP), also known as cholestasis of pregnancy, is a form of cholestasis that develops in pregnancy, usually during the second or third trimester. While it typically resolves after giving birth, it increases the risk of adverse maternal and fetal outcomes.

Scientists don’t know exactly what causes cholestasis in pregnancy, but they believe a combination of genetic, hormonal, and environmental factors influence the risk. Genetic susceptibility and reproductive hormones, especially estrogen, are thought to be the main cholestasis of pregnancy causes.

Estrogen, which can affect levels of proteins involved in bile transport, is highly produced during the late stages of pregnancy. This may cause bile to accumulate and impair bile flow during pregnancy in genetically susceptible women.

Moreover, ICP rates vary across different ethnicities, geographical regions, and seasons, being higher in Hispanic and Swedish people, as well as during the winter season. This further supports the role of genetic and environmental factors in the development of ICP.

Risk factors of ICP include:

South American or Northern European ancestry
certain genetic factors
personal or family history of ICP
current or past history of other liver diseases, including hepatitis C and fatty liver disease
pregnancies involving more than one baby (i.e., twins, triplets)
pregnancy at an older age, such as over 35.

Extrahepatic cholestasis causes

Extrahepatic cholestasis often arises due to physical blockages, inflammation, or abnormal narrowing (called strictures) of the bile ducts outside the liver, impairing bile flow. Possible extrahepatic cholestasis causes include:

tumors or cysts (fluid-filled sacs) in the extrahepatic bile ducts or pancreas
other masses and tumors that put pressure on these ducts
gallstones, or hardened bile deposits that form in the gallbladder and can become stuck in bile ducts outside the liver
pancreatitis, or inflammation of the pancreas
certain diseases affecting the extrahepatic bile ducts, including PSC and extrahepatic biliary atresia
previous surgery or injury near the extrahepatic bile ducts.

Risk factors

There are a variety of risk factors that may influence a person’s chances of developing cholestasis, which can vary based on the underlying cholestasis causes. Some general cholestasis risk factors include:

chronic liver diseases or other conditions linked to cholestasis
genetic factors linked to a risk of liver diseases or to drug-induced liver injury
prolonged parenteral nutrition
use of medications that have been linked to cholestasis, especially for long periods of time or at high doses.

Lifestyle factors such as obesity, sedentary habits, excessive and prolonged alcohol consumption, and smoking, may also increase the risk of cholestasis-causing diseases, or exacerbate their severity.

The risk of cholestasis is typically similar in men and women. However, disease forms caused by pregnancy, biliary atresia, PBC, and medication use are exclusive to or more common in women, while cholestasis caused by PSC is more frequent in men.

In turn, children are generally more susceptible to the disease than adults because their liver is still immature.

Preventing cholestasis

Depending on its underlying cause, cholestasis can’t always be prevented. In general, there is no way to prevent ICP or genetic liver diseases that may cause cholestasis.

But there are some steps that can be taken to promote liver health and minimize risk factors. Cholestasis prevention measures may include:

maintaining good nutrition and eating a healthy diet
partaking in regular exercise
avoiding alcohol, tobacco, and other substances that may damage the liver
getting regular checkups to evaluate liver health, especially for those with a family history or other risk factors of liver diseases or cancer
being cautious with medications that could cause cholestasis, and taking all medications as prescribed by a doctor
getting vaccinated against hepatitis A and B.

You should always let a healthcare provider know if you’re experiencing possible symptoms of cholestasis or other liver problems. A doctor can help come up with a management strategy for preventing these problems from progressing or minimizing their impact.

Liver Disease News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.