Cholestasis

Cholestasis is an alteration (partial or total) in the biliary flow to the duodenum.

Bile is a bitter-tasting yellowish fluid produced by the liver. It is stored in the gallbladder and flow to the intestine to help in digestion, with the main function of converting fats into fatty acids.

Cholestasis is a condition caused by the interruption in the flow of bile to the duodenum. It may be due to a defect in the bile synthesis in the liver (intrahepatic cholestasis) or due to a bile duct obstruction (extrahepatic cholestasis).

Cholestasis is generally characterized by an elevation of serum conjugated (or direct) bilirubin.

Cholestasis can be classified, based on the causes, into the following types:

• Intrahepatic cholestasis: The obstruction of the biliary flow is located in the liver within the liver parenchyma:
  • Hepatocellular causes (viral hepatitis, alcoholic hepatitis, Zellweger syndrome).
  • Diffuse disorders (lymphoma, amyloidosis, infiltrative hepatocellular carcinoma)
  • Hepatic excretory defect (medication, cholestasis of pregnancy)
  • Compression/inflammation of the bile ducts (primary biliary cirrhosis, sclerosing cholangitis, liver transplant rejection, acute cholangitis, Caroli disease)
  • Stauffer syndrome is an unusual case of intrahepatic cholestasis due to a form of paraneoplastic syndrome (triggered by an abnormal response to a cancerous tumor).
• Extrahepatic cholestasis: The obstruction of the biliary flow is located in the bile ducts. The most common causes are:
  • Gallstones and choledocholithiasis (gallstones within the common bile duct)
  • Inflammatory diseases and carcinomas of the bile ducts.
  • Extrinsic compression of the biliary tree (pancreatic cancer, pancreatitis).

Several drugs may induce cholestasis as a side effect such as chlorpromazine, phenylbutazone, oral contraceptives or antidepressants (amitriptyline, imipramine).

One of the causes previously mentioned is the cholestasis of pregnancy that often develops during the second and third trimesters of pregnancy. The reason behind is that pregnancy increases the sensitivity of the bile ducts.

The most common symptoms of cholestasis are:

• Jaundice (yellowing of the skin and eyes).
• Acholia (pale stools).
• Choluria (dark urine).
• Abdominal pain (in the right upper quadrant).
• Itching.

In addition to the clinical history and physical examination, additional tests are required.

Cholestasis main feature is an increase in the conjugated (or direct) bilirubin.

Bilirubin is a brownish yellow by-product of red blood cell destruction at the end of their life cycle. The bilirubin, created from red blood cell degradation, is not water-soluble and it is called unconjugated or indirect bilirubin. This type of bilirubin is later processed in the liver, where it becomes water-soluble and it is called conjugated or direct bilirubin.

In case of suffering from cholestasis, there is an increase in total bilirubin in a blood test (hyperbilirubinemia) due to an increase in the conjugated or direct bilirubin.

Besides, for a proper diagnosis the following tests may be useful:

• Blood tests: There is an increase in alkaline phosphatase and gamma glutamyl transpeptidase (GGT). There is also a prolonged prothrombin time.
• Imaging tests: Ultrasonic scanning (most widely used) that may be complemented with computed tomography and magnetic resonance cholangiography
• Liver biopsy.

The best practice is the treatment of the underlying disorder.

If the cause is extrahepatic, persistent and surgically remediable, it is important to proceed with surgery promptly to avoid secondary hepatocellular failure. If the cause is intrahepatic, however, the disorder is not benefited by surgery, both because of the possibility of causing liver and renal failure and the absence of useful relieving surgical procedures.

For the itching, keep the skin hydrated and the use of mild soaps is recommended.

Cholestyramine, antihistamines and ursodeoxycholic acid may be a help.

Cholestasis, not properly treated, may cause the following complications:

• Liver failure
• Portal hypertension
• Hepatic encephalopathy