Direct bilirubin test explained

Bilirubin is formed as old red blood cells break down; at first it is indirect (unconjugated) and travels in the blood attached to a protein. Liver cells join it with glucuronic acid — a process called conjugation — and this produces direct (conjugated) bilirubin, which is water-soluble and is excreted in bile into the gut, where it gives stools their brown colour. A rise in direct bilirubin therefore points to a problem after the liver's conjugation step — either in the liver cells themselves (hepatitis, cirrhosis) or along the path bile takes to drain (stones, a narrowed duct, a pancreatic or gallbladder tumour). This differs from the breakdown of blood cells, which raises indirect bilirubin. Some of the already-conjugated bilirubin that has not managed to leave in the bile passes back into the blood and urine, so when there is an obstruction the urine darkens and the stools become pale. Direct bilirubin is usually assessed together with total bilirubin, ALT, AST, GGT and alkaline phosphatase, so that it is clear whether the problem is in the liver cells or in bile drainage.

• When total bilirubin is raised and it has to be worked out which part — direct or indirect — is driving the result
• With jaundice, dark urine or pale stools — signs of an obstruction to bile flow
• When liver disease (hepatitis, cirrhosis) is suspected — as part of liver tests
• When gallstones, a narrowed duct or a tumour are suspected, with pain on the right side under the ribs
• To monitor the course of already known liver or gallbladder disease

A raised direct bilirubin points to a problem after the liver's conjugation step — liver cell disease (hepatitis, cirrhosis) or an obstruction of bile flow (stones, a narrowed duct, a pancreatic or gallbladder tumour). Unlike indirect bilirubin, it does not usually rise from the breakdown of blood cells alone. It is often accompanied by jaundice, dark urine and pale stools.

• Liver cell disease — hepatitis, cirrhosis
• A narrowing of the bile ducts
• Gallstones blocking the flow of bile
• A pancreatic or gallbladder tumour

Symptoms that may go with a raised result

• Jaundice — yellowing of the skin and the whites of the eyes
• Dark urine, pale stools
• Itching
• Pain on the right side under the ribs

What to discuss with a doctor

• ALT, AST, GGT and alkaline phosphatase — these help to tell liver cell disease from an obstruction of bile flow
• Total and indirect bilirubin — whether only the direct fraction is raised, or both
• An abdominal ultrasound scan, if an obstruction in the bile ducts is suspected
• When to repeat the test, so that the change over time can be seen

A low or normal direct bilirubin is usually not a cause for concern — only a raised value is clinically meaningful. MedlinePlus notes that a low bilirubin is most often not a reason to worry and is sometimes linked to certain medicines that affect the result.

• The effect of some classes of medicine on the test result — antibiotics, contraceptive pills, sleeping tablets, anti-seizure medicines
• Physiological variation — a low reading on its own is most often not a sign of disease

What follows a low result

• A low direct bilirubin usually needs no further testing, if the other liver markers are normal
• If you take medicines that could affect the result, mention this to your doctor
• Repeat the test only if there are other symptoms or changes in other markers

Direct, total and indirect bilirubin

Total bilirubin is the sum of the direct and the indirect fraction. Indirect bilirubin is formed as blood cells break down, before the liver processes it; direct bilirubin has already been joined with glucuronic acid in the liver and is ready to be removed in bile. That is why the direct fraction says something about the liver cells and about bile drainage, while indirect bilirubin is raised by the breakdown of blood cells.