All the following data is from a task a professor gave me and is not connected to a true patient.

Patient's bilirubin level is first 28 micromole/litre and direct bilirubin level is 8 micromole/litre. Three weeks after the first blood test, the patient takes another blood test. This time, total bilirubin level is 48 micromole/litre and direct bilirubin is 9 micromole/litre, meaning that indirect bilirubin level increased by 19 micromole/litre during these three weeks. Liver enzymes (AST, ALT, ALP, GGT) were within normal range both times. Iron wasn't measured the first time, it was normal the second time. What are the likeliest causes for this?

FIRST EDIT: The patient took the first blood test on full stomach and the second one on empty stomach. It's most likely not Gilbert's syndrome because direct bilirubin is also high, although the fact that the increase of bilirubin is mild and that it's higher after not eating may point to Gilbert's syndrome.

SECOND EDIT: I have done some research on the effect of fasting on bilirubin level in patients with Gilbert's syndrome. I have found that after eating 400 kcal per day for two days, indirect bilirubin should be twice as high as the baseline level in a GS patient (The inverse starving test is not a suitable provocation test for Gilbert's syndrome). This patients indirect bilirubin level is twice as high after just about 8 hours of not eating if we assume that the bilirubin level from the first blood test is the baseline level. Considering this, taking the second blood test on an empty stomach is most likely not the cause of the elevation of indirect bilirubin and so the elevation is most likely not a sign of Gilbert's syndrome.

  • 1
    Is this a real person or hypothetical?
    – Carey Gregory
    Commented Jul 15, 2020 at 18:11
  • It's from a task a professor gave us. It's not Gilbert's syndrome. Commented Jul 15, 2020 at 18:56
  • 2
    When you ask academic questions like this, it would be helpful if you made it clear you're not asking about a real person because we have a strong policy against providing personal medical advice.
    – Carey Gregory
    Commented Jul 16, 2020 at 4:49

1 Answer 1


It is impossible to make a definite diagnosis based solely on the given data. But there are some likely options which should all be checked. Here are the possibilities and test which should be done to check them:

  1. Bilirubin is a product of erythrocyte breakdown. That's why predominantly unconjugated hyperbilirubinemia could be a symptom of hemolysis or dyserythropoiesis which are simple to check. The patient should check their reticulocyte level (which should be high as the bone marrow tries to compensate for the breakdown of erythrocytes), lactate dehydrogenase level (which should be high because it's a product of erythrocyte breakdown, especially if hemolysis in intravascular), haptoglobin level (which should be low because of an increase of free hemoglobin which binds to haptoglobin). The patient should also check their hemoglobin level which should be elevated in case of intravascular hemolysis, but will be normal if hemolysis is extravascular. If any of the mentioned substances aren't within normal range, peripheral blood smear test should be further made to check for abnormalities of red blood cells. (Hemolytic Anemia: Evaluation and Differential Diagnosis)
  2. Any type of viral hepatitis could be the reason for elevated bilirubin. Viral markers should be checked. (Wikipedia - Hyperbilirubinemia)
  3. Any biliary stricture can cause a moderate rise in bilirubin level. This includes gallstones, benign and malignant tumors (pancreatic adenocarcinoma or cholangiocarcinoma). Portosystemic shunt could also cause elevated indirect bilirubin because some amount of blood with indirect bilirubin would bypass the liver and the process of conjugation. (Wikipedia - Hyperbilirubinemia) Both of these conditions can be seen with ultrasonography. However, these conditions are not likely because biliary strictures predominantly cause conjugated hyperbilirubinemia. (Biliary strictures: diagnostic considerations and approach) Still, they should be checked because these conditions are very serious.
  4. The patient should be asked about their history of drug use. Some medications, such as gemfibrozil, irinotecan and the protease inhibitors, atazanavir, and indinavir, can elevate the level of unconjugated bilirubin because they reduce the hepatic uptake of it. (Evaluating Elevated Bilirubin Levels in Asymptomatic Adults) The patient should also be asked whether they have had any surgeries or suffered any traumas lately which could cause hematoma which is connected to erythrocyte breakdown and consequently a rise in unconjugated bilirubin.
  5. If all of previous conditions don't exist then we can suppose that the patient has either Gilbert's or syndrome or Crigler-Najjar syndrome. If indirect bilirubin continues to rise and rises above 85 micromole/litre we can suppose that the patient has Crigler-Najjar syndrome and if the value is lower than 85 micromole/litre we can suppose that the patient has Gilbert's syndrome. Both of the syndromes are mostly harmless in adults. Potential jaundice can be treated with phenobarbital. Both syndromes can be definitely proven with genetic tests. (Evaluating Elevated Bilirubin Levels in Asymptomatic Adults)

If there are some other possible causes which I missed, please write another answer or let me know in the comments.

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