What is the diagnosis of Gilbert's syndrome?

From the Guidelines

Gilbert's syndrome is a benign genetic condition that does not require specific treatment, and patients with this diagnosis should be reassured that it is a common, harmless condition affecting approximately 5-10% of the population. The elevated bilirubin levels occur due to a genetic variation that reduces the activity of the enzyme UGT1A1, which is responsible for conjugating bilirubin in the liver 1. Symptoms may include mild jaundice (yellowing of the skin or eyes) during periods of stress, illness, fasting, or physical exertion, but many people remain asymptomatic.

Key Considerations

• Patients with Gilbert's syndrome should be aware that certain medications metabolized by the UGT1A1 enzyme might need dosage adjustments 1.
• Maintaining good hydration, regular meals, and avoiding prolonged fasting can help minimize episodes of jaundice.
• No dietary restrictions or lifestyle modifications are necessary beyond these simple measures.
• Regular medical follow-up is generally not required specifically for Gilbert's syndrome.

Diagnosis and Management

• Diagnosis of Gilbert's syndrome can be presumed by calculating the amount of conjugated bilirubin, which is normally less than 30% of the total bilirubin, in the absence of haemolysis 1.
• Where Gilbert's syndrome is present, or any causes of haemolysis, eligibility (and on-study management) should focus on elevations of direct bilirubin rather than total bilirubin.
• It is essential to differentiate Gilbert's syndrome from other causes of hyperbilirubinemia, such as drug-induced liver injury (DILI), to avoid unnecessary diagnostic testing and incorrect assignment of causality 1.

From the Research

Diagnostic Criteria for Gilbert's Syndrome

The diagnosis of Gilbert's syndrome is typically based on the presence of mildly elevated total bilirubin with normal serum activities of liver transaminases, biliary damage markers, and red blood cell counts 2. The syndrome is characterized by a mild, lifelong, unconjugated hyperbilirubinemia in the absence of haemolysis or evidence of liver disease 3.

Key Features of Gilbert's Syndrome

Some key features of Gilbert's syndrome include:

• Asymptomatic sporadic episodes of jaundice due to a mild unconjugated hyperbilirubinemia caused by a deficiency in bilirubin glucoronidation 4
• Bilirubin levels typically do not exceed 3 mg/dl, but higher levels have been reported in rare cases 4
• Normal values of liver enzymes and no overt signs of hemolysis 5
• Impaired bilirubin glucuronidation due to mutations in the TATA box upstream of the uridine diphosphoglucose glucuronyltransferase gene 3

Diagnostic Tests for Gilbert's Syndrome

Several diagnostic tests can be used to confirm the presence of Gilbert's syndrome, including:

• Rifampicin test and caloric restriction test, which are non-invasive and can help avoid hazardous liver biopsy 5
• Genetic testing to identify mutations in the UGT1A1-gene, which can be useful in some cases 4, 6
• Analysis of the promoter region of the UGT1A1-gene to identify A(TA)(7) TAA alleles, which are associated with Gilbert's syndrome 6

Prevalence and Clinical Significance of Gilbert's Syndrome

Gilbert's syndrome is a relatively common condition, with a prevalence of approximately 3.2-8.6% in healthy individuals 6. It is also a frequent cause of unconjugated hyperbilirubinemia in children after orthotopic liver transplantation 6. The syndrome has been associated with a reduced prevalence of chronic diseases, including cardiovascular diseases and type 2 diabetes mellitus 2.