OVERVIEW

What is Gilbert's Syndrome?

Gilbert's syndrome is the most common congenital non-hemolytic jaundice, also known as benign unconjugated hyperbilirubinemia or idiopathic unconjugated hyperbilirubinemia. Commonly referred to as constitutional jaundice, it was first reported by the French physician Gilbert in 1901, hence the name.

This condition is caused by reduced or deficient activity of the liver enzyme UDP-glucuronosyltransferase, leading to impaired uptake of indirect bilirubin by liver cells. Its hallmark is a mild elevation of serum total bilirubin, primarily due to increased unconjugated bilirubin.

Gilbert's syndrome is present from birth, but most cases are not diagnosed early and are typically detected during adolescence. It is more common in males, with clinical manifestations including long-term intermittent mild jaundice. Most patients have no obvious symptoms, though mild fatigue, poor appetite, and discomfort in the liver area may occur. There is currently no effective treatment.

Is Gilbert's Syndrome a Genetic Disease?

It is an autosomal recessive genetic disorder, with numerous reports of familial cases both domestically and internationally.

Does Gilbert's Syndrome Have Age or Gender Predilection?

Jaundice usually appears around the age of 10, often with a positive family history. It is more common in males than females.

Is Gilbert's Syndrome Highly Prevalent?

This condition has been reported worldwide, with an incidence rate of 4%–16% in the general population. It is more prevalent in males, with a male-to-female ratio of approximately 10:1.

The wide variation in reported incidence rates and the significant gender disparity may be due to the fact that many cases of Gilbert's syndrome, particularly in females (since males naturally have slightly higher bilirubin levels than females), exhibit only very mild bilirubin elevation, often going unnoticed and undiagnosed.

SYMPTOMS

What are the manifestations of patients with Gilbert's syndrome?

• The typical symptom is recurrent yellowing of the skin and sclera, often triggered or worsened by fatigue, stress, alcohol consumption, menstruation in women, or concurrent infections. Most patients experience no subjective discomfort, or only mild fatigue and abdominal discomfort when jaundice deepens, with overall good health. More often, there is no visible skin yellowing, and elevated bilirubin levels are only detected during physical examinations.

• In terms of physical signs, patients show no cirrhosis or splenomegaly.

• Laboratory tests reveal that, apart from elevated indirect (unconjugated) bilirubin, other liver function indicators are essentially normal. Bilirubin levels are generally below three times the upper limit of normal (≤3mg/dL), but may fluctuate to 5–8mg/dL under triggers like fatigue, alcohol consumption, or infections.

Does Gilbert's syndrome affect intelligence? Will it shorten lifespan?

Although Gilbert's syndrome is present at birth, significant bilirubin elevation typically appears during adolescence or later, and the increase is usually mild. By then, the nervous system is fully developed, so intelligence is unaffected. The condition also does not reduce lifespan.

In essence, apart from occasional mild skin yellowing, individuals with Gilbert's syndrome are nearly indistinguishable from the general population. The only difference is that certain drugs, such as irinotecan, may pose a higher risk of toxicity in these patients.

CAUSES

What factors are associated with the occurrence of Gilbert's syndrome?

Current research indicates that the occurrence of Gilbert's syndrome is primarily related to genetic factors, such as impaired bilirubin glucuronidation and certain gene defects.

DIAGNOSIS

How is Gilbert's Syndrome Diagnosed?

When a patient presents with chronic intermittent episodes of jaundice without other symptoms, good overall health, and liver function tests showing only elevated indirect bilirubin—while other types of jaundice have been ruled out—Gilbert's syndrome or other rare congenital non-hemolytic jaundice conditions should be considered. A positive family history is also common in Gilbert's syndrome.

Additionally, a positive fasting test (serum indirect bilirubin levels doubling after 24 hours of fasting) or positive phenobarbital test (significant decrease in indirect bilirubin after oral phenobarbital administration) and positive rifampin test can aid in diagnosis.

The rifampin test (oral administration of 600mg rifampin, measuring unconjugated bilirubin levels at 2, 3, 4, and 24 hours post-dose) is a simple, non-invasive, and highly accurate method for diagnosing GS, often prioritized internationally as the first-line diagnostic approach.

Definitive diagnosis relies on liver biopsy to assess UDP-glucuronosyltransferase (UGT) expression levels and gene mutations. However, laboratory testing is generally unnecessary for diagnosing Gilbert's syndrome, as it does not alter management or lifespan.

A clinical diagnosis of Gilbert's syndrome can be made when no other causes of jaundice are identified and symptom patterns align with the condition.

TREATMENT

How should Gilbert's syndrome be treated?

There is currently no cure for this condition.

The prognosis is good, as it does not lead to chronic hepatitis, cirrhosis, or increase the risk of liver malignancy, and no special treatment is required. If the jaundice caused by elevated bilirubin is unacceptable, eliminating triggers, resting, and increasing caloric intake can help. If necessary, phenobarbital can be used to induce UGT activity and promote bilirubin excretion.

Patients with Gilbert's syndrome should maintain healthy lifestyle habits, avoid triggers that worsen jaundice, prevent fatigue and alcohol consumption, and seek timely diagnosis and treatment for infections such as fever, cough, or abdominal pain and diarrhea.

What should patients with Gilbert's syndrome pay attention to when treating other diseases?

Theoretically, the use of certain medications (such as some chemotherapy drugs and protease inhibitors) in patients with Gilbert's syndrome may increase the risk of adverse drug reactions. Currently, the confirmed risk is primarily an increased toxic reaction to irinotecan.

Therefore, during treatment for other diseases, patients must inform their attending physician of their detailed medical history, monitor medication use carefully, and avoid irinotecan whenever possible.

DIET & LIFESTYLE

None yet.

PREVENTION

None.