Gilbert syndrome, pronounced “zheel-BAYR,” is a common, mild genetic condition in which the liver does not properly process a substance called bilirubin. Bilirubin is a yellowish waste product that is created when the body breaks down old red blood cells.

To understand Gilbert syndrome, it is essential to understand how the body normally handles bilirubin.

• Production: Your body is constantly breaking down old red blood cells. One of the byproducts of this process is a toxic, fat-soluble form of bilirubin called unconjugated bilirubin.
• Transport: This unconjugated bilirubin travels through the bloodstream to the liver for processing.
• Processing (Conjugation): In the liver, a specific enzyme works to attach a chemical tag to the bilirubin. This enzyme is called uridine diphospho-glucuronosyltransferase, or UGT. This tagging process, known as conjugation, makes the bilirubin water-soluble and non-toxic.
• Excretion: This new, “tagged” conjugated bilirubin is then excreted from the liver into the bile, passes through the intestines, and is eliminated from the body, giving stool its characteristic color.

A helpful analogy is to think of your liver as a sophisticated recycling and waste management plant.

• Old red blood cells are the “garbage trucks” that are taken out of service each day. Breaking them down produces a greasy, toxic yellow sludge (unconjugated bilirubin).
• This sludge is sent to a special processing station in the liver. At this station, a highly efficient worker (the UGT enzyme) sticks a water-soluble “shipping label” onto each molecule of sludge. This labeled package (conjugated bilirubin) can then be safely mixed with water and shipped out of the body through the bile ducts.
• In Gilbert syndrome, this specific worker is not sick or lazy; they just work at about 70% of the normal speed due to a minor genetic variation.
• Because the worker is a bit slow, a small backlog of the greasy, yellow sludge can build up in the blood, especially during times when the body is under stress and producing more “garbage.” This slight backlog of unconjugated bilirubin is what can cause the mild, fluctuating jaundice seen in the condition.

In my experience, many patients discover they have Gilbert syndrome only after routine blood tests show slightly elevated bilirubin levels, usually without any symptoms.

The cause of Gilbert syndrome is a mildly reduced activity of the UGT1A1 enzyme. This is the specific enzyme in the liver responsible for conjugating bilirubin. The reduction in enzyme activity is not a sign of liver damage; the liver cells are perfectly healthy. The enzyme itself is structurally normal, but it is produced at a slightly lower level than average.

This reduced production is caused by a common genetic variation in the promoter region of the UGT1A1 gene. The promoter region of a gene acts like a “volume dial.” In people with Gilbert syndrome, this dial is simply set a bit lower, leading to the production of a reduced, but still functional, amount of the UGT1A1 enzyme. This is a stable, lifelong trait, not a disease that worsens over time.

In my experience, individuals are born with it, it’s inherited from both parents, although many remain unaware of it unless tested during unrelated medical evaluations.

Gilbert syndrome is an inherited genetic condition. It is not contagious and is not caused by any lifestyle factor or exposure.

• Inheritance Pattern: It is inherited in an autosomal recessive pattern. This means that for a person to have the reduced enzyme activity of Gilbert syndrome, they must inherit two copies of the specific UGT1A1 gene variant, one from their mother and one from their father.
• Prevalence: This genetic variant is extremely common, and it is estimated that Gilbert syndrome affects anywhere from 5% to 10% of the population, making it a very common condition. It is more frequently diagnosed in men than in women, possibly due to hormonal differences. The condition is often first discovered during routine blood tests in late adolescence or early adulthood.

In my experience, this condition is inherited in an autosomal recessive manner and is often diagnosed incidentally, especially in young adults.

The single most important feature of Gilbert syndrome is that the vast majority of people who have it are completely asymptomatic and are unaware they have the condition.

The only true sign or symptom of Gilbert syndrome is intermittent, mild jaundice. Jaundice is the yellowing of the skin and, more noticeably, the whites of the eyes (a condition called scleral icterus).

• This jaundice is caused by the mild buildup of unconjugated bilirubin in the blood.
• It is transient, meaning it comes and goes.
• It is harmless. The level of bilirubin elevation is not high enough to cause any of the toxic effects seen in newborns with severe jaundice.

The mild jaundice in Gilbert syndrome is often not noticeable under normal conditions. It may only become apparent during times of physical stress, which can temporarily increase the rate of red blood cell breakdown or put a strain on the liver’s processing capacity.

Common triggers that can cause a temporary increase in bilirubin and make the jaundice more noticeable include:

• Illness: Infections like a cold or the flu.
• Fasting or Skipping Meals.
• Dehydration.
• Strenuous Physical Exertion.
• Stress.
• Menstruation.

Some individuals with Gilbert syndrome report vague, non-specific symptoms like fatigue, weakness, or abdominal discomfort, but large-scale studies have not shown a clear and consistent link between these symptoms and the syndrome itself.

Clinically, I reassure patients that symptoms like fatigue or abdominal discomfort are not directly caused by Gilbert syndrome in most cases, though they may be reported.

Gilbert syndrome is almost always diagnosed as an incidental finding on a routine blood test performed for another reason. The diagnosis is made by a doctor based on a characteristic and reassuring pattern of blood test results.

The Diagnostic Blood Test Pattern

A diagnosis of Gilbert syndrome can be confidently made when a blood test shows:

1. A mildly elevated level of total bilirubin, with the majority of it being the unconjugated type.
2. All other standard liver function tests such as ALT, AST, and ALP are completely normal.
3. A complete blood count (CBC) is normal, with no signs of hemolysis (abnormal red blood cell destruction).

This specific pattern, an isolated elevation of unconjugated bilirubin with all other liver and blood tests being normal is the key to the diagnosis. It tells the doctor that the liver is not inflamed, damaged, or blocked, and that the body is not breaking down red blood cells at an abnormal rate. The problem is isolated to a mild inefficiency in bilirubin processing.

In a patient with this classic laboratory pattern, no further testing, such as an ultrasound, liver biopsy, or genetic testing, is necessary to confirm the diagnosis.

In my experience, genetic testing is rarely needed, clinical history, normal physical exam, and routine labs are usually enough to confirm the diagnosis.

Gilbert syndrome is a benign, harmless condition that requires absolutely no medical treatment.

The most important part of “treatment” is education and reassurance from a healthcare provider. Once a diagnosis is confirmed, the doctor’s primary role is to explain to the patient that they do not have a liver disease, that their condition is a harmless genetic quirk, and that it will not cause any long-term health problems or affect their lifespan.

Important Considerations for Medication

The only clinically significant aspect of living with Gilbert syndrome is an awareness of its effect on the metabolism of certain medications.

• The UGT1A1 enzyme, which is less active in people with Gilbert syndrome, is also responsible for breaking down and eliminating several specific drugs.
• Because the enzyme works more slowly, people with Gilbert syndrome may be more susceptible to developing higher blood levels and increased side effects from these specific medications.
• The most well-known example is irinotecan, a chemotherapy drug used to treat colon cancer. Patients with Gilbert syndrome often require a lower dose of this drug to avoid severe side effects like diarrhea.
• Some medications used to treat HIV may also be affected.

It is important for individuals with a diagnosis of Gilbert syndrome to inform all of their doctors and pharmacists about their condition so that it can be taken into account if they need to be prescribed new medications in the future.

Clinically, I’ve found that education is the most powerful tool, patients feel relieved knowing the condition is harmless and doesn’t require ongoing treatment.

Discovering that you have an abnormal blood test result can be a source of significant worry. However, a diagnosis of Gilbert syndrome should be a cause for relief. It is a common, harmless, and lifelong genetic trait that results in a slightly slower processing of bilirubin by the liver. It does not represent liver disease, it does not cause any serious health problems, and it does not shorten a person’s life. The only management required is an awareness of the condition, particularly when starting certain new medications. In my experience, Gilbert syndrome is one of the most benign causes of jaundice and patients benefit greatly from understanding its harmless nature.

The National Institutes of Health, MedlinePlus. (2023). Gilbert syndrome. Retrieved from https://medlineplus.gov/genetics/condition/gilbert-syndrome/

American Liver Foundation. (n.d.). Gilbert Syndrome. Retrieved from https://liverfoundation.org/liver-diseases/gilbert-syndrome/

The Mayo Clinic. (2022). Gilbert’s syndrome. Retrieved from https://www.mayoclinic.org/diseases-conditions/gilberts-syndrome/symptoms-causes/syc-20372811