From the Guidelines
Gilbert's syndrome is associated with unconjugated hyperbilirubinemia. This condition is a common, benign genetic disorder that affects approximately 5-10% of the population, resulting from a reduced activity of the enzyme UDP-glucuronosyltransferase (UGT1A1), which is responsible for conjugating bilirubin in the liver 1. The deficiency in this enzyme leads to an accumulation of unconjugated (indirect) bilirubin in the bloodstream. Patients with Gilbert's syndrome typically have mild elevations in total bilirubin levels, with the unconjugated fraction predominating.
Key Characteristics of Gilbert's Syndrome
- Reduced activity of the enzyme UDP-glucuronosyltransferase (UGT1A1)
- Accumulation of unconjugated (indirect) bilirubin in the bloodstream
- Mild elevations in total bilirubin levels (usually 1-3 mg/dL)
- Unconjugated fraction predominating
- Generally asymptomatic, but may experience mild jaundice during periods of stress, fasting, illness, or physical exertion
Diagnosis and Management
Diagnosis of Gilbert's syndrome can be determined by calculating the proportion of conjugated bilirubin, which should be less than 20-30% of the total bilirubin 1. Genetic testing for DNA mutations of uridine 5'-diphospho-glucuronyl-transferase may be considered for definitive confirmation. Management of Gilbert's syndrome is generally not required, as it is a benign condition with no negative health consequences. However, it is essential to distinguish Gilbert's syndrome from other causes of hyperbilirubinemia, such as drug-induced liver injury (DILI), to ensure appropriate management and prevent unnecessary diagnostic testing or treatment 1.
From the Research
Gilbert's Syndrome and Hyperbilirubinemia
- Gilbert's syndrome is associated with unconjugated hyperbilirubinemia, as evident from studies 2, 3, 4, 5, 6.
- The syndrome is characterized by a mild elevation of systemic unconjugated bilirubin levels, in the absence of underlying liver or overt hemolytic disease 2, 4, 5.
- The condition is caused by a mutation of the specific UDP glucuronosyl transferase conjugating bilirubin with glucuronic acid, resulting in reduced activity of this enzyme 3, 4.
Key Findings
- Patients with Gilbert's syndrome have a high fraction of unconjugated bilirubin, normal values of liver enzymes, and no overt signs of hemolysis 2.
- Phenobarbital treatment can significantly reduce the level of unconjugated serum bilirubin in patients with Gilbert's syndrome 2, 6.
- Gilbert's syndrome is considered a rather benign disorder without the necessity of any therapeutic intervention 4.
- Recent studies suggest that individuals with Gilbert's syndrome may benefit from the mild hyperbilirubinemia and are protected from the development of various diseases 5.