An Overview of Cholestasis

Cholestasis is a reduction (or cessation) in the flow of bile. Cholestasis can occur at any age in both males and females. This can happen for several different reasons. Cholestasis can occur from impairment of bile secretion from the liver cells, an obstruction that blocks the flow of bile, or a combination of the two.

Bile is a greenish-brown fluid that aids in digestion and is secreted by the liver and stored in the gallbladder. The lack of any of the substances that are normally secreted into bile can cause cholestasis. These substances include:

• Water
• Cholesterol
• Lecithin (a phospholipid)
• Bile pigments (bilirubin and biliverdin)
• Bile salts and bile acids (sodium glycocholate and sodium taurocholate)
• Copper and other excreted metals (in small amounts)

Symptoms

Bile works in the small intestine to help breakdown and absorb fats into the body. When cholestasis occurs, the flow of bile is impaired at some point between the liver cells (where the bile is produced) and the small intestine (the duodenum) where the bile is secreted to help breakdown fats.

When the flow of bile is blocked or reduced for any reason, bilirubin begins to escape into the bloodstream and starts to build up, which eventually causes the yellowish hue to the skin and whites of the eyes, as found in jaundice.

Other symptoms may include:

• Dark urine
• Yellowish hue to the whites of the eyes and skin
• Foul-smelling and/or light-colored stool (from a blockage of bilirubin into the intestine)
• Steatorrhea (too much fat in the stool from the inability of the bile to digest fats in the intestine)
• Itchiness (possibly from bile products accumulating in the skin)
• Abdominal pain
• Fatigue
• Nausea
• Jaundice (from an excess of bilirubin)
• Low calcium and vitamin D levels and other nutrients (if cholestasis is long-term)
• Muddy-colored skin, fatty yellow deposits in the skin (form long-term cholestasis)

Other symptoms (depending on the cause) may include nausea, vomiting, or fever. Cholestasis can occur in men and women of any age. Adults with long-term (chronic) cholestasis are often free of symptoms.

Terminology

To fully understand the function of the liver and of bile, it’s important to be aware of some of the common terminology of the liver and its adjacent organs.

• Liver: A large lobed glandular organ in the abdomen, involved in many metabolic processes (such as breaking down fats to produce energy). The cells of the liver produce bile.
• Bile: A substance made in the liver cells, stored and secreted by the gallbladder that is critical to the body for normal digestion and absorption of fats and fat-soluble vitamins such as vitamin D and vitamin K.
• Bile Duct: Serves to carry bile from the liver and the gallbladder to the duodenum (the first section of the small intestine).
• Pancreatic Duct: The primary duct of the pancreas that empties into the small intestine through an opening shared with the common bile duct.
• Extrahepatic Bile Ducts: Small tubes that carry bile outside of the liver.
• Pancreas: A large gland behind the stomach that secretes enzymes (such as lipase) that work with bile to help break down fats.
• Bile acids: Bile contains bile acids, which are critical for digestion and absorption of fats and fat-soluble vitamins in the small intestine.
• Bilirubin: An orange/yellowish colored pigment that is made in the liver when hemoglobin is broken down, then excreted in bile. When the normal flow of bile is stopped (due to an obstruction or other cause) bilirubin escapes into the bloodstream and accumulates causing symptoms of jaundice.
• Hemoglobin: A protein that carries oxygen in the blood, hemoglobin gets recycled and the body saves its iron content for future use. The waste product from the breakdown of hemoglobin (which occurs in the liver) is bilirubin.
• Gallbladder: The small sac-shaped organ beneath the liver in which bile is stored after secretion by the liver and before release into the small intestine.
• Gallstone: An abnormal, small, hard mass made of bile pigments, cholesterol and calcium salts, which is formed in the gallbladder or bile ducts. Gallstones can cause a blockage of the bile duct (resulting in severe pain and cholestasis).
• Liver Cirrhosis: A condition in which long-term damage (of liver cells) causes the liver to no longer function properly. This damage results in scar tissue, which replaces the normal liver tissue.
• Jaundice: A medical condition (commonly seen in cholestasis) involving yellowing of the skin or the whites of the eyes. Jaundice occurs due to the excess in bilirubin pigment, typically caused by an obstruction of the bile duct or liver disease.

Causes

Various conditions of the liver, the bile duct, or the pancreas can cause a decrease in the flow of bile and result in cholestasis. An obstruction in the flow of any of the substances that make up bile (including bile salts, bile acids, and more) can result in cholestasis.

Causes of cholestasis may include a problem with the liver itself, or a condition occurring outside of the liver.

Causes Within the Liver (Intrahepatic):

• Acute hepatitis
• Alcohol-induced liver disease
• Drug use
• Genetic abnormalities
• Liver cirrhosis due to viral hepatitis B or C
• Any condition that results in inflammation or scarring of the bile ducts (such as hepatitis)
• Hormone effects on bile flow such as during pregnancy (a specific condition called cholestasis of pregnancy)
• Cancer that involves the liver
• Certain prescription medications

Causes Outside the Liver (Extrahepatic Cholestasis):

• A stone in the bile duct causing a narrowing and obstruction of bile flow (gallstones)
• Cancer of the bile duct (tumors that restrict bile flow)
• Cysts that restrict the flow of bile
• Inflammation of the pancreas (pancreatitis)
• Cancer of the pancreas

Medications

The liver is the organ involved in removing toxic substances such as those in many drugs, including prescription medications. Some medications are harder for the liver to break down and may even become toxic to the liver. According to a study published by the British Medical Journal (BMJ), medications that can damage the liver include:

• Analgesics including paracetamol, aspirin, and non-steroidal anti-inflammatory drugs (such as Motrin)
• Cardiac (Heart) Drugs: methyldopa, amiodarone
• Psychotropic Drugs: MAO inhibitors, phenothiazines (such as chlorpromazine)
• Other Drugs: sodium valproate, estrogens (oral contraceptives and hormone replacement therapy)

Diagnosis

A complete medical history and physical exam will be part of a diagnostic assessment for cholestasis. The primary goal of diagnosis when a person has symptoms of jaundice is to decipher whether the cause stems from inside or outside of the liver. 

There are many tests used to diagnose cholestasis, including lab tests such as:

• Blood tests such as bilirubin levels (measures the severity of cholestasis, but not the cause)
• Liver function tests to evaluate whether the liver is properly functioning and measure Alkaline phosphatase (ALP) and Gamma-glutamyltransferase (GGT) — enzymes that are high in people with cholestasis
• Imaging tests, such as ultrasonography, if the blood tests are abnormal — a CT scan or an MRI may be done along with the ultrasonography to positively establish the underlying cause of cholestasis
• Liver biopsy to check for liver cancer in some instances
• If the cause of cholestasis is a blockage of the bile ducts, more precise images of the ducts will be needed via a procedure using a flexible tube with a viewing tube called an endoscope

Treatment

Treatment of cholestasis depends on the underlying cause, these include:

• Medication, such as cholestyramine, to relieve the itching of the skin
• Surgery or endoscopy (a flexible viewing tube with a surgical instrument attached) to correct blockages of the bile duct
• Vitamin K administration to improve blood clotting (unless there is severe liver damage)
• The cessation of any prescription medications that could be toxic to the liver
• Discontinuing any illicit substance that is toxic to the liver (such as alcohol and drugs)
• Vitamin D or other supplements
• Cholesterol medication
• Cholecystectomy (removal of the gallbladder)
• Biliary stenting (to allow proper flow of bile)
• Lithotripsy (to break up any gallbladder stones)
• Consultation with a hepatologist (liver specialist) or other specialists

If hepatitis is the underlying cause, cholestasis will subside once the hepatitis is cleared up.

Prevention and Natural Interventions

Prevention measures to address the underlying cause which may include:

• Self-care
• Hepatitis vaccine
• Avoid heavy drinking or drug use (particularly IV drugs)
• Seek medical attention as soon as possible with early signs of cholestasis (such as jaundice and itchy skin)
• Avoid diets that are high in fat and cholesterol and low in fiber as well as quick weight loss diets (particularly for those previously diagnosed with gallstones)

A Word From Verywell

Recovery from cholestasis is dependent on many factors including the underlying cause and how severe the condition was before its diagnosis. If the cause of cholestasis is a blockage from gallstones, those can be surgically removed, and relatively quick and full recovery can be expected. If the cause is damage to the liver from chronic alcohol use, the result may be liver cirrhosis, which may be too severe to expect any type of quick recovery. Be sure to discuss your individual case and your options with your healthcare provider.