From the Guidelines
No, conjugated bilirubin is not increased in Gilbert's syndrome. Gilbert's syndrome is characterized by a mild, chronic unconjugated hyperbilirubinemia, meaning there is an elevation in unconjugated (indirect) bilirubin while conjugated (direct) bilirubin levels remain 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 activity of this enzyme, typically about 30% of normal, results in decreased bilirubin conjugation and subsequent mild elevation of unconjugated bilirubin in the blood.
Some key points to consider in the diagnosis of Gilbert's syndrome include:
- The condition is present in up to around 10% of the population [ 1 ]
- Total bilirubin levels in Gilbert's Syndrome are usually mildly elevated, but rarely greater than 4-5 mg/dL [ 1 ]
- 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 ]
- If conjugated bilirubin is elevated, other liver conditions should be considered rather than Gilbert's syndrome.
Gilbert's syndrome is benign and typically requires no treatment, with bilirubin levels usually staying below 3 mg/dL [ 1 ]. The condition may become more apparent during periods of fasting, illness, or stress, when bilirubin levels can temporarily increase. It is essential to accurately identify Gilbert's Syndrome in clinical trials, especially clinical trials in cholestatic liver diseases, as misdiagnosis may result in unnecessary diagnostic testing, incorrect assignment of causality, as well as drug interruption or discontinuation [ 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, patients with chronic persistent hepatitis, and patients with chronic hemolysis 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, 5.
- Genotyping the UGT1A1 promoter polymorphism can help predict elevated and fluctuating bilirubin levels and diagnose Gilbert's syndrome 5.
Key Findings
- Studies have consistently shown that Gilbert's syndrome is characterized by an elevated level of unconjugated bilirubin, rather than conjugated bilirubin 6, 2, 3, 4, 5.
- The diagnosis of Gilbert's syndrome can be confirmed by the presence of a typical serum bilirubin pattern, with a high proportion of unconjugated bilirubin 3.
- The UGT1A1*28 promoter polymorphism is a useful biomarker for diagnosing Gilbert's syndrome and predicting elevated bilirubin levels 4, 5.