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Gilbert’s syndrome is a very common and entirely harmless inherited condition that causes bilirubin to rise slightly in the blood. If your blood test showed a mildly elevated bilirubin and you were told about this syndrome, you can rest easy: it is not a liver disease, it causes no harm, and it needs no treatment.
Many people with Gilbert’s syndrome occasionally notice a faint yellow tinge in the whites of the eyes (the sclerae) or in the skin, without any other symptom. It is so common that an estimated 5 to 10% of the population has it. Recognizing it matters above all to avoid unnecessary tests and workups.
What is Gilbert’s syndrome?
It is a genetic variant, not a disease. People with Gilbert’s syndrome are born with lower activity of the enzyme that processes bilirubin in the liver. As a result, bilirubin builds up a little more than usual, but the liver works completely normally and no damage develops over the years.
It is inherited, so it is common to find more than one family member with the same tendency to have a slightly high bilirubin. It usually becomes apparent after puberty and is more common in men.
Why does it happen?
Bilirubin is the product of the normal breakdown of hemoglobin from red blood cells. The liver takes it up and “conjugates” it, meaning it attaches it to glucuronic acid to make it water-soluble so it can be cleared into the bile. The enzyme responsible for that step is UGT1A1 (uridine diphosphate glucuronosyltransferase 1A1).
In Gilbert’s syndrome there is a variant in the UGT1A1 gene that reduces production of this enzyme, generally to around 70% of normal activity. Because less bilirubin is conjugated, the indirect (unconjugated) fraction rises in the blood. There is no obstruction and no destruction of liver cells: the process simply runs more slowly.
What situations raise bilirubin?
In people with Gilbert’s syndrome, mild jaundice tends to appear or become more noticeable in circumstances that place extra demand on the body. The most common are:
- Prolonged fasting or very low-calorie diets.
- Infections or febrile illness.
- Physical or emotional stress and lack of sleep.
- Intense exercise.
- Surgery or dehydration.
- Menstruation, in some women.
In all of these situations, bilirubin drops back on its own once the trigger resolves. It is not a sign that the liver is failing.
Prolonged fasting can make the rise in bilirubin more evident in Gilbert’s syndrome.
How is it diagnosed?
The most common scenario is the incidental finding of a raised bilirubin on a blood test (for example, a biochemistry panel) ordered as a routine check or for symptoms unrelated to the liver. That finding causes anxiety in the patient and sometimes leads a physician unfamiliar with the condition to request a battery of tests that are not needed.
The pattern that confirms the diagnosis is simple:
- Total bilirubin is raised, driven by indirect (unconjugated) bilirubin.
- Direct (conjugated) bilirubin is normal.
- Total bilirubin rarely exceeds 5 mg/dL.
- The rest of the liver panel is normal: liver enzymes (SGOT and SGPT), alkaline phosphatase, GGT, albumin and prothrombin time.
A complete blood count is usually added to rule out hemolysis (accelerated destruction of red blood cells), which can also raise indirect bilirubin. With this clinical and laboratory picture, the diagnosis is straightforward and, in most cases, neither genetic testing nor a liver biopsy is needed.
Does it need treatment?
No. Gilbert’s syndrome needs no treatment and no special diet, and it does not require limiting physical activity or lifestyle. Frequent follow-up is not needed either. It is enough to know you have it and to explain it when a high bilirubin turns up on a test. Far from being a problem, there is evidence that mildly elevated bilirubin may even have an antioxidant, protective effect against some cardiovascular diseases.
Does it have any practical consequence?
The one situation worth keeping in mind is the use of certain medications. Because the UGT1A1 enzyme is also involved in metabolizing some drugs, people with Gilbert’s syndrome may process them more slowly. The most relevant example is irinotecan, a chemotherapy agent used in cancer, with which people carrying certain UGT1A1 variants have a higher risk of side effects. For this reason, oncology sometimes tests the UGT1A1 gene before prescribing it, in order to adjust the dose. If you have Gilbert’s syndrome, it is worth mentioning it to your doctor before starting chemotherapy or a new treatment.
See also
References
- Vítek L, Tiribelli C. Gilbert's syndrome revisited. J Hepatol. 2023;79(4):1049-1055.
- Huang MJ, Chen PL, Huang CS. Bilirubin metabolism and UDP-glucuronosyltransferase 1A1 variants in Asians: pathogenic implications and therapeutic response. Kaohsiung J Med Sci. 2022;38(8):729-738.
- Goluch Z, Wierzbicka-Rucińska A, Książek E. Nutrition in Gilbert's Syndrome: a systematic review of clinical trials according to the PRISMA statement. Nutrients. 2024;16(14):2247.
- Abdullah-Koolmees H, et al. Pharmacogenetics guidelines: overview and comparison of the DPWG, CPIC, CPNDS, and RNPGx guidelines. Front Pharmacol. 2021;11:595219.
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