Finding a raised bilirubin on a blood test can show that there is a change at one of the stages of bilirubin’s production, its processing by the liver, or its removal from the body through the bile.
A raised bilirubin can sometimes come from a harmless condition such as Gilbert’s syndrome, and sometimes from conditions involving the liver or the bile ducts.
A raised bilirubin is not on its own a diagnosis of liver disease or a blocked bile duct.
What matters is how high the bilirubin is, whether the rise is in the direct or the indirect fraction, and what the other liver tests show.
What is bilirubin?
Bilirubin is a yellow substance produced when ageing red blood cells break down.
The bilirubin produced is carried in the blood to the liver. The liver processes it and passes it into the bile. It then reaches the bowel and is removed from the body.
A change at any stage of this system can cause bilirubin to rise in the blood.
What do total, direct and indirect bilirubin mean?
Laboratory results usually show three different terms:
- Total bilirubin — the total amount of bilirubin in the blood.
- Direct bilirubin — bilirubin that has been processed, that is conjugated, by the liver.
- Indirect bilirubin — bilirubin not yet conjugated in the liver.
This distinction is quite valuable when the cause of a raised bilirubin is being investigated.
Why does indirect bilirubin rise?
One of the important causes of a raised indirect bilirubin is Gilbert’s syndrome. Apart from that, a rise in indirect bilirubin can be caused by:
- Red blood cells breaking down faster than normal (haemolysis)
- Some blood disorders
- Some medicines
- Rarer conditions affecting the processing of bilirubin in the liver
What is Gilbert’s syndrome?
Gilbert’s syndrome is a quite common, inherited and generally harmless condition.
Because of a slight reduction in the liver’s capacity to process bilirubin, the indirect bilirubin in particular rises from time to time. The person’s other liver tests are usually normal.
Bilirubin can rise further in situations such as:
- Going without food for a long time
- Dehydration
- A febrile illness
- Intense exercise
- Stress
Some people notice slight yellowing of the whites of the eyes.
Gilbert’s syndrome does not lead to progressive liver damage or cirrhosis. It usually needs no particular treatment.
But rather than someone with a first raised bilirubin telling themselves “I have Gilbert’s”, the other causes need ruling out properly.
Why does direct bilirubin rise?
A raised direct bilirubin can be seen particularly in conditions involving the liver and the bile ducts. These include:
- Acute or chronic hepatitis
- Liver damage from medicines
- Stones in the bile ducts
- Narrowing or blockage of the bile ducts
- Cholangitis
- Some conditions of the pancreas
- Other conditions affecting the liver and bile ducts
For this reason, where direct bilirubin is raised, it matters to weigh the ALP, GGT, ALT and AST results together with it.
Do gallstones raise bilirubin?
Yes.
If a stone from the gallbladder drops into the main bile duct and blocks the flow of bile, bilirubin can rise. In that case there may be:
- Yellowing of the eyes and skin
- Darkening of the urine
- Paling of the stool
- Pain in the right upper abdomen
If fever and shivering are added to a blocked bile duct, that matters particularly.
Does a raised bilirubin cause jaundice?
Yes.
When bilirubin rises above a certain level, yellowing becomes noticeable first in the whites of the eyes and then in the skin. But with a mildly raised bilirubin there may be no visible jaundice.
So the reasoning “my eyes are not yellow, so a raised bilirubin does not matter” is not correct.
Can darkening of the urine be related to bilirubin?
Yes.
When direct bilirubin in particular rises, the urine can become dark yellow or the colour of tea. Indirect bilirubin, being insoluble in water, does not pass into the urine.
So dark urine can be an important clue when the type of raised bilirubin is being assessed. But dehydration can also darken the urine.
Does paling of the stool matter?
Yes.
If markedly less bile reaches the bowel, the normal brown colour of the stool can become paler.
Jaundice, dark urine and pale stools together can be seen where the flow of bile is obstructed, and should be assessed.
Can anaemia raise bilirubin?
In some kinds of anaemia, red blood cells break down faster than normal. This is called haemolysis. In haemolysis the indirect bilirubin in particular can rise.
Where needed, your doctor may use tests such as:
- Full blood count
- Reticulocyte count
- LDH
- Haptoglobin
Can medicines raise bilirubin?
Yes.
Some medicines can affect bilirubin metabolism, liver cells or the flow of bile. This is why it matters to tell your doctor about:
- Prescribed medicines
- Over-the-counter medicines
- Vitamins
- Herbal products
- Supplements
Do not stop your medicine on your own
Do not stop a medicine you are taking because your bilirubin came back high.
How is the cause of a raised bilirubin looked into?
Your doctor will first look at the distribution between total, direct and indirect bilirubin. Then, where needed, the following may be assessed:
- ALT
- AST
- ALP
- GGT
- Full blood count
- LDH and other tests for haemolysis
- Hepatitis tests
- Abdominal ultrasound
If needed, CT, MRI/MRCP, EUS or other investigations may be carried out.
Not every raised bilirubin needs all of these tests.
Does it matter if bilirubin is only a little high?
A mild and particularly an isolated rise in indirect bilirubin, with the other liver tests normal, can come from harmless causes such as Gilbert’s syndrome.
By contrast, if a raised bilirubin is accompanied by a raised ALT/AST, a raised ALP/GGT, abdominal pain, fever or jaundice, other causes need looking into.
So looking at the bilirubin number alone is not enough.
When is urgent assessment needed?
Assessment is needed without delay if a raised bilirubin or jaundice is accompanied by any of the following:
Seek assessment without delay
Jaundice together with fever and shivering · jaundice together with severe right upper abdominal pain · confusion or excessive sleepiness · severe and persistent vomiting · rapidly deepening jaundice · vomiting blood or black stools.
Jaundice + fever/shivering + right upper abdominal pain together in particular may call for urgent assessment for an infection of the bile ducts (acute cholangitis).
What should you do if bilirubin is raised?
- Do not panic. A raised bilirubin has harmless causes too.
- Look at direct and indirect bilirubin. Which fraction has risen helps determine the cause.
- Weigh the other liver tests together. ALT, AST, ALP and GGT give important clues.
- Find your previous results. Whether bilirubin has been raised before matters.
- Tell your doctor about the medicines you take. Including herbal products and supplements.
- Do not wait if there is jaundice, fever or severe pain. Urgent assessment may be needed.
Remember
- An isolated raised indirect bilirubin Can come from harmless causes such as Gilbert’s syndrome.
- A raised direct bilirubin May call for conditions of the liver or bile ducts to be looked into.
- Dark urine, pale stools and jaundice Matter for a disturbance in the flow of bile.
- A raised bilirubin Does not on its own mean liver failure or cancer.
- Jaundice, fever or shivering and abdominal pain May call for urgent assessment.
This is not enough to make a diagnosis
What a raised bilirubin means is determined by weighing the total, direct and indirect bilirubin levels, the ALT, AST, ALP and GGT results, the patient’s symptoms, the medicines they take and, where needed, imaging findings.
Diagnosing yourself with liver or bile duct disease from a single raised bilirubin result is not the right course.
Sources
- Prof. Ali Tüzün İnce, MD