From the Guidelines
No, conjugated bilirubin is not increased in Gilbert's syndrome. Gilbert's syndrome is characterized by a mild elevation in unconjugated (indirect) bilirubin, typically less than 3 mg/dL, while conjugated (direct) bilirubin remains normal [ 1 ]. This occurs due to a genetic deficiency in the enzyme UDP-glucuronosyltransferase 1A1 (UGT1A1), which is responsible for conjugating bilirubin in the liver. The reduced enzyme activity (about 30% of normal) leads to decreased bilirubin conjugation and subsequent mild unconjugated hyperbilirubinemia.
Key Characteristics of Gilbert's Syndrome
- Affects approximately 5-10% of the population [ 1 ]
- More commonly diagnosed in males
- Benign and requires no treatment
- Fasting, stress, illness, or physical exertion may temporarily worsen the hyperbilirubinemia
- Laboratory tests typically show normal liver function tests aside from the elevated unconjugated bilirubin
- Diagnosis is confirmed by calculating the amount of conjugated bilirubin, which should be less than 20%-30% of the total bilirubin, in the absence of haemolysis [ 1 ]
Clinical Implications
- Misdiagnosis may result in unnecessary diagnostic testing, incorrect assignment of causality, as well as drug interruption or discontinuation
- Accurate identification of Gilbert's Syndrome is important in clinical trials, especially clinical trials in cholestatic liver diseases
- Conjugated bilirubin levels are not increased in Gilbert's syndrome, and this distinction is crucial for diagnosis and management [ 1 ]
From the Research
Bilirubin Levels in Gilbert's Syndrome
- The level of conjugated bilirubin in Gilbert's syndrome is not increased, as studies have shown that the concentration of total conjugates is comparable to the values in healthy control subjects 2.
- In Gilbert's syndrome, the fraction of conjugated relative to total bilirubins is markedly decreased due to the increased concentration of unconjugated pigment 2.
- The relative proportion of unconjugated bilirubin in serum is higher in patients with Gilbert's syndrome, ranging from 90 to 99% of total bilirubin, compared to healthy subjects and patients with other conditions 3.
- The UGT1A1*28 promoter polymorphism is associated with a decrease in bilirubin glucuronidation activity, leading to an increase in the level of unconjugated bilirubin in Gilbert's syndrome 4.
- Studies have shown that the biliary pigment pattern in Gilbert's patients is characterized by a lower proportion of bilirubin diglucuronide and a higher proportion of bilirubin monoglucuronide, indicating a defect in the conjugation process 5.
Key Findings
- The concentration of conjugated bilirubin is not increased in Gilbert's syndrome 2, 5.
- The level of unconjugated bilirubin is increased in Gilbert's syndrome due to a decrease in bilirubin glucuronidation activity 2, 4.
- The biliary pigment pattern in Gilbert's syndrome is abnormal, with a lower proportion of bilirubin diglucuronide and a higher proportion of bilirubin monoglucuronide 5.