Cholestasis diagnosis

Last updated Jan. 17, 2025, by Lindsey Shapiro, PhD
Fact-checked by Marta Figueiredo, PhD

Diagnosing cholestasis, a condition in which the flow of the digestive fluid bile from the liver to the intestines is slowed or stalled, often involves a series of tests to assess liver health and the potential presence of blockages in the bile ducts.

Cholestasis can be intrahepatic or extrahepatic, depending on whether it occurs inside or outside the liver, and has many possible causes. These include side effects of certain medications, pregnancy-related hormones, bile duct blockages, or other chronic liver diseases such as progressive familial intrahepatic cholestasis (PFIC), biliary atresia, Alagille syndrome, alcohol-related liver disease, hepatitis, and primary biliary cholangitis (PBC).

Management of these distinct conditions can vary, so part of the diagnostic process for cholestasis is to identify its underlying cause.

Cholestasis can lead to the toxic accumulation of bile in the liver, which can cause serious and irreversible liver damage if left untreated. An early and accurate cholestasis diagnosis is therefore critical for maintaining liver health and avoiding serious liver problems in the long term.

Signs and symptoms leading to diagnosis

While the symptoms of cholestasis can vary based on the underlying cause, there are a few common symptoms that might prompt suspicion of the condition:

• jaundice, or a yellow discoloration of the skin and whites of the eyes
• pale-colored stools
• dark-colored urine
• itchy skin, or pruritus.

In intrahepatic cholestasis of pregnancy (ICP) — a form of cholestasis that develops during pregnancy — the most noticeable symptom is usually pruritus, but other cholestasis symptoms such as jaundice and changes in urine or stool color are also possible.

If a person is experiencing symptoms of cholestasis, it is important to inform a doctor as soon as possible so the physician can help diagnose the condition, establish its underlying cause, and come up with an appropriate treatment plan.

Initial steps for diagnosing cholestasis

If a person has signs of cholestasis, a doctor will first collect a detailed medical history to better understand which symptoms the person has been experiencing and for how long. They’ll ask questions to identify if there are underlying risk factors for the condition, such as the use of certain medications, alcohol consumption, recent biliary surgery, or a family history of inherited forms of cholestasis. This can also help them narrow down what the underlying cause of cholestasis might be.

This will be followed by a physical examination to assess for signs and symptoms of cholestasis. During the physical exam, doctors are looking for things such as:

• signs of jaundice
• abdominal pain or tenderness
• an enlarged liver.

Diagnostic tests for cholestasis

If a person has symptoms of cholestasis, a doctor will likely order liver function tests and a number of other diagnostic tests to look for potential biliary obstructions and their cause. Achieving a cholestasis diagnosis may involve:

• blood tests
• imaging tests
• endoscopic exams to look inside the body with a camera
• liver biopsy.

Blood tests

A doctor may initially order blood tests to evaluate a person’s liver function and to check for signs that the bile ducts are obstructed. Some things that might be checked for in cholestasis blood tests are:

• levels of alkaline phosphatase and gamma-glutamyl transpeptidase, two liver enzymes that are very elevated in cholestasis.
• levels of bilirubin, a yellow-reddish waste product that’s normally incorporated into bile and excreted through feces, but backs up into the bloodstream in cholestasis
• blood clotting, as many clotting players are produced by the liver or absorbed in the intestines through the action of bile.

Imaging studies

If blood tests are abnormal and suggest cholestasis, imaging tests will usually be run to visualize the liver and bile ducts and determine where the problem starts. This will help to discriminate intrahepatic from extrahepatic cholestasis.

Imaging studies for cholestasis often involve an abdominal ultrasound, which uses sound waves to create pictures of internal organs in the abdomen. CT or MRI scans might also be used. These scans can show whether there are bile duct obstructions, such as gallstones — hardened bile deposits that become stuck in the bile ducts — and tumors, or inflammation in the bile ducts.

If any abnormalities are observed, a doctor might order more specialized imaging tests to look at the bile ducts in more detail.

• A hepatobiliary iminodiacetic acid (HIDA) scan uses a radioactive tracer and an X-ray to visualize the movement of bile from the liver, through the bile ducts, and to the small intestine. If the dye doesn’t move as expected through the biliary system, it could be a sign of an obstruction that’s causing cholestasis.
• Magnetic resonance cholangiopancreatography, or MRCP, is a specialized type of MRI scan that uses a dye to better visualize abdominal structures and identify the cause and location of a biliary obstruction.

Specialized tests

In some cases, doctors may run more specialized tests to determine the underlying cause of cholestasis.

Some causes of cholestasis, such as PFIC and Alagille syndrome, are hereditary, and genetic testing for mutations associated with these conditions can help establish a diagnosis.

For pregnant women, a serum bile acids test, which measures bile acid levels in the blood, is the most accurate way to diagnose ICP. Bile acids are components of bile that leak to and accumulate in the bloodstream when the flow of bile is stalled. In ICP, the level of total bile acids is usually very high.

Other causes of cholestasis have specific tests that can be run to establish a cholestasis diagnosis. Doctors may prescribe tests to detect antibodies against certain microbes — including cytomegalovirus, hepatitis viruses, and Toxoplasma gondii — that are known to cause cholestasis.

The autoimmune disease PBC is characterized by the presence of specific self-reactive antibodies that can be measured in a blood test. And  alpha-1 antitrypsin deficiency, a metabolic condition known to cause cholestasis, can be diagnosed by measuring the blood levels of the alpha-1 antitrypsin enzyme.

Invasive diagnostic procedures

If cholestasis is suspected based on the results of blood tests and noninvasive imaging, more invasive procedures might be performed to get more information about the cause of cholestasis.

Endoscopic retrograde cholangiopancreatography (ERCP) is a minimally invasive test that involves inserting an endoscope — a thin, flexible tube with a tiny camera on the end — through the mouth and into the small intestines. A dye that can be visualized with an X-ray is then injected through the endoscope into the bile ducts. This allows doctors to clearly visualize the biliary system on an X-ray and identify where any potential blockages are occurring.

In addition to its diagnostic potential, an ERCP can be used to collect a tissue biopsy and treat certain things that may be causing cholestasis. For example, it can be used to remove a gallstone, or to insert a tube (stent) that helps widen narrowed bile ducts.

If results from noninvasive testing do not suggest extrahepatic cholestasis, doctors can request a liver biopsy, in which a sample of liver tissue is collected and sent to the lab for analysis. The procedure usually involves inserting a thin needle through the abdomen and into the liver to collect a small liver sample.

A biopsy can show abnormalities that are specific to several causes of intrahepatic cholestasis, including biliary atresia and PBC. It is also the best method to assess the extent and severity of liver damage, scarring, and inflammation.

Challenges in diagnosing cholestasis

A cholestasis differential diagnosis is the process by which doctors identify the specific cause of cholestasis, considering the wide range of conditions that can cause acute and chronic forms of cholestasis. In addition to conditions exclusively affecting the liver or the bile ducts, possible causes include whole-body diseases like infections, Alagille syndrome, sarcoidosis, and cystic fibrosis.

This can make it more difficult for doctors to establish the presence of cholestasis and its underlying cause. Some causes of cholestasis are rare, and even if cholestasis is identified, it might not be easy to determine exactly what is causing it.

A delayed or improper cholestasis diagnosis can prevent the initiation of potentially life-saving treatments in many forms of cholestasis. This is especially important when the disease affects infants, whose liver is more susceptible to damage due to the immaturity of pathways involved in bile acid production and metabolism.

If cholestasis is suspected or a person is experiencing symptoms of a liver disease without a known cause, reaching out to specialists such as hepatologists or gastroenterologists (liver and gastrointestinal specialists, respectively) who understand how cholestasis is diagnosed and treated can increase the chances of the right diagnosis being reached promptly.

What to do after a cholestasis diagnosis

After receiving a cholestasis diagnosis, patients should be referred promptly to specialists with experience in managing the condition. They’ll help come up with appropriate treatments for cholestasis based on its underlying cause.

Some causes of cholestasis, such as biliary atresia, require prompt surgical intervention. In other forms of cholestasis, medications and lifestyle changes to manage symptoms will be the first-line approach.

Studies have shown ICP can have adverse outcomes both in the mother and fetus. Women who have cholestasis while pregnant should work closely with liver specialists and maternal-fetal medicine doctors, who specialize in high-risk pregnancies. They will develop a treatment and monitoring plan to ensure the health of both the mother and fetus during pregnancy and childbirth. This may involve inducing labor early, depending on a woman’s symptoms and the risk to the developing fetus.

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