Cholestasis

What is cholestasis?

Cholestasis is the slowing or stalling of bile flow from your liver. Your liver produces bile and delivers it to your digestive system through a network of vessels called bile ducts. Bile ducts run through your liver (intrahepatic ducts) as well as outside of it (extrahepatic ducts). They connect your liver, gallbladder, pancreas and small intestine. These organs and bile ducts make up your biliary system.

When bile can’t flow properly through your biliary system, it affects all of these organs and vessels. Bile backs up in your bile ducts and organs, irritating the tissues and interfering with their function. Bile also begins to leak into your bloodstream, which has a toxic effect. It causes uncomfortable symptoms, and eventually, illness. Cholestasis can be a temporary problem or an ongoing and worsening one.

How does cholestasis affect my body?

In the short term, cholestasis affects the organs in your biliary system. Backed-up bile can cause inflammation in your liver, gallbladder, pancreas or bile ducts. This may cause pain, nausea and other symptoms. It also makes infections more likely. Cholestasis affects your small intestine by depriving it of the bile it needs to break down fats in your food. This may cause symptoms of indigestion and diarrhea.

As cholestasis goes on, these more immediate effects can lead to longer-term consequences. Bile accumulating in your blood can cause symptoms of illness, jaundice and severe itching. Chronic inflammation in any of your organs can lead to permanent scarring, which impairs their function. Malabsorption of fat-soluble vitamins (E, D, K and A) can lead to malnutrition and failure to thrive in children.

Is cholestasis life-threatening?

Cholestasis itself isn’t a primary cause of death, though some of its downstream effects can be. Liver diseases that cause cholestasis can also lead to permanent liver failure. Many causes are curable or temporary, including pregnancy. However, cholestasis in pregnancy is associated with an increased risk of life-threatening complications for both the birthing parent and the fetus. Risks include preeclampsia, premature birth and stillbirth.

What is the main cause of cholestasis?

Cholestasis has many causes. In general, two types of problems may be going on. It may be a problem with your liver that inhibits its ability to secrete bile into your bile ducts. (This causes intrahepatic cholestasis, bile stasis inside your liver.) Or it may be a problem in your bile ducts that’s physically restricting the flow of bile through the ducts. (This causes extrahepatic cholestasis, bile stasis in the ducts outside of your liver.)

What are the possible causes of extrahepatic cholestasis vs. intrahepatic cholestasis?

Causes affecting your liver (intrahepatic causes) include:

Chronic liver disease. Chronic liver disease that lasts a long time can cause scarring of the liver tissues (cirrhosis), including the intrahepatic bile ducts. Scarring causes them to narrow, which restricts the flow of bile. Specific diseases may also damage the cells that produce bile in more specific ways. Some of these diseases include:

• Chronic hepatitis B.
• Chronic hepatitis C.
• Autoimmune hepatitis.
• Alcohol-induced hepatitis.
• Nonalcoholic steatohepatitis.
• Primary biliary cholangitis.
• Primary sclerosing cholangitis.
• Progressive familiar intrahepatic cholestasis.

Acute hepatitis. Acute liver inflammation (from a recent, temporary condition) can cause your liver to swell, inhibiting bile flow. Various toxins and infections may also cause the cells that produce bile to malfunction in different ways. Acute causes of hepatitis include:

• Alcohol poisoning.
• Toxic hepatitis.
• Viral hepatitis.
• Mononucleosis.
• HIV.
• Cytomegalovirus (CMV).
• Liver cancer.
• Lymphoma.
• Sepsis.
• Gallbladder infection.

Pregnancy. Cholestasis of pregnancy (also called obstetric cholestasis) occurs in some people during the third trimester, when estrogen levels are at their highest. High estrogen inhibits bile secretion in your liver. Obstetric cholestasis goes away by itself after you’ve delivered your baby.

Total parenteral nutrition. Being fed through an IV in your vein bypasses your entire digestive system, including the hormonal signals that trigger your biliary system. If there’s no food in your small intestine that needs bile to help break it down, your liver might not get the message to keep delivering bile. This can cause bile to back up in your liver.

Medications. Certain medications can also cause bile stasis in your liver. If your liver is having trouble metabolizing these medications, they can have a toxic effect. Some of these medications include:

• Birth control pills.
• Anabolic steroids.
• Amoxicillin and other penicillin antibiotics.
• Azathioprine, an immunosuppressant.
• Imipramine, an antidepressant.
• Estradiol, a type of hormone replacement therapy.
• Cimetidine, used to treat stomach ulcers.
• Tolbutamide, used to treat type 2 diabetes.
• Terbinafine, an antifungal
• Certain antipsychotic drugs, including chlorpromazine and prochlorperazine.

Causes affecting your extrahepatic bile ducts include:

Biliary stricture. Chronic inflammation in your bile ducts can cause scarring and narrowing of the ducts, restricting bile flow. Causes of stricture include:

• Prior surgery or injury.
• Chronic pancreatitis.
• Pancreatic cancer.
• Bile duct cancer.
• Cholangitis.
• Biliary atresia.

Bile duct obstructions. Physical obstructions may affect your bile ducts from the inside or outside, including:

• Gallstones in your common bile duct (choledocholithiasis).
• Gallstones in your cystic duct or Hartmann’s pouch (Mirizzi syndrome).
• Pancreatic cysts and pseudocysts.
• Extrahepatic bile duct tumors.

What are the symptoms of cholestasis?

The most typical symptoms include:

• Jaundice. A yellow tint to your skin and in the whites of your eyes is usually one of the first signs that your liver isn’t functioning properly. Jaundice is caused by the buildup of bile in your blood. Specifically, the yellow comes from bilirubin, one of the ingredients in bile. Some bilirubin also comes out in your pee, which may give it a darker color.
• Light-colored poop. You may also notice poop changes due to the absence of bile in your intestines. When bile can’t flow to your intestines to help break down fats, these fats come out in your poop. Fatty stools are whitish or clay-colored. Their light color comes from the absence of bilirubin, which usually makes them brown. They may also float and may be extra smelly.
• Pruritus. Skin itching (pruritus) is another common symptom of cholestasis. Bile-related pruritus is caused by the buildup of bile salts in your blood. The bile salts (or bile acids) irritate nerves in your peripheral nervous system, causing itching. There’s no rash with this type of pruritus. Some people seem to be more sensitive to bile salts than others, and pruritus may be mild to severe. Some people itch more in their hands, feet, arms or legs, and others itch all over.

You may have other symptoms related to the cause of your cholestasis, such as:

• Abdominal pain.
• Nausea and vomiting.
• Fatigue.

How is cholestasis diagnosed?

Blood tests

If you have symptoms of cholestasis, your healthcare provider will begin their investigation by testing a sample of your blood. They’ll look for high levels of bilirubin and bile salts. They may also see elevated levels of cholesterol and certain liver enzymes, such as gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP). These clues can tell them more about the possible causes of your condition.

Imaging tests

If your blood tests are positive, your healthcare provider will investigate further with imaging tests that visualize your biliary system. They may begin with simple, noninvasive tests such as an abdominal ultrasound or abdominal CT scan. These can show physical obstructions in your bile ducts and swelling from inflammation in your organs. They can indicate where the problem is coming from.

Depending on what they find or don’t find, they may need to use a more specific test that visualizes your bile ducts in more detail. A HIDA scan involves injecting a radiotracer into one of your veins before taking images. The tracer follows the pathway bile takes through your biliary system. Sometimes healthcare providers use MRI (magnetic resonance imaging) to look more specifically at your biliary system.

Exploratory exams

Some causes of cholestasis may require internal exploration to find and fix them. Your healthcare provider may need to explore your bile ducts or take a liver biopsy, a sample of your liver tissue to test in the lab. Endoscopic exams are procedures that look inside your body with an endoscope, a tiny camera on the end of a long tube. During an ERCP (endoscopic retrograde cholangiopancreatography), healthcare providers can find and fix problems in your bile ducts through the endoscope.

How is cholestasis treated?

Acute causes

Fixing cholestasis depends on fixing the underlying cause. Some causes are relatively easy to fix. Medications causing problems can be swapped for alternatives. Infections can be treated with antibiotics or antivirals. Physical obstructions can be treated by endoscopic procedures, such as ERCP. Your healthcare provider can remove blockages and open up narrowed passageways with stents.

Chronic causes

Causes related to chronic liver diseases may be more difficult to treat. Some diseases have no known cure, and scarring of the liver tissues (cirrhosis) isn’t reversible. Lifestyle changes, such as diet, exercise and avoiding alcohol, can help slow the course of many liver diseases. In the meantime, your healthcare provider will focus on treating the side effects of your condition. Treatment may include:

• Nutrition. Dietary changes and supplements can help compensate for malabsorption and vitamin deficiencies.
• Ursodeoxycholic acid. This medication, which is usually used to dissolve gallstones, can sometimes help cholestasis by increasing bile production and mediating the effects of extra bile salts in your blood.
• Naltrexone. This opioid antagonist is sometimes prescribed to treat severe pruritus. It works by blocking the pathways to the nerves that are irritated by bile acids in your blood. Pruritus isn’t a histamine-related itch, so typical itching relief medications (antihistamines) don’t help.
• Cholestyramine. This cholesterol medication can help bind cholesterol to bile salts in your intestines so that more comes out in your poop and less is reabsorbed into your blood. It may help with hyperlipidemia and with pruritus.

What is the outlook for this condition?

This depends on the cause, how long it has been going on, and how much scarring you have in your liver, bile ducts or other organs. Some cases can be cured completely. Others may require lifelong treatment. If you have severe irreversible damage to one of your organs, it might need to be removed or replaced. Surgery may be a cure in some cases, or it may help to delay the progression of your disease.

A note from Cleveland Clinic

Cholestasis begins in your biliary system, but it has consequences for your entire body. Bile that can’t flow where it needs to will cause problems where it doesn’t belong. It backs up into your organs, builds up in your blood and causes inflammation and illness. The lack of bile in your digestive system can cause long-term nutritional deficiencies that affect your bones, vision and blood.

It may take time for these effects to cause noticeable symptoms. Vague abdominal discomfort or nausea might be too easy to overlook. When you begin to see signs of bile building up in your blood — yellowing in your eyes, or color changes in your poop or pee — it’s time to seek immediate attention. Whatever the cause, treating cholestasis sooner than later leads to better outcomes.