Is conjugated bilirubin increased in Gilbert's syndrome?

From the Guidelines

Conjugated bilirubin is typically not increased in Gilbert's syndrome. Gilbert's syndrome is characterized by mild, intermittent unconjugated hyperbilirubinemia, with total bilirubin levels usually between 1-3 mg/dL. The key feature is that the elevation occurs primarily in the unconjugated (indirect) bilirubin fraction, while conjugated (direct) bilirubin remains normal. This pattern occurs because Gilbert's syndrome involves a genetic deficiency in the enzyme UDP-glucuronosyltransferase 1A1 (UGT1A1), which is responsible for conjugating bilirubin in the liver. This enzyme deficiency reduces the liver's ability to process unconjugated bilirubin into its conjugated form, leading to higher levels of unconjugated bilirubin in the bloodstream. If conjugated bilirubin is elevated, other liver conditions should be suspected instead of Gilbert's syndrome, such as viral hepatitis, drug-induced liver injury, or obstructive biliary disease.

According to the most recent study 1, diagnosis of Gilbert's Syndrome should be determined by calculating the proportion of conjugated bilirubin, which should be less than 20%-30% of the total bilirubin. This is consistent with other studies 1, which also suggest that conjugated bilirubin is not typically increased in Gilbert's syndrome.

Some key points to consider when evaluating patients with suspected Gilbert's syndrome include:

• Calculating the proportion of conjugated bilirubin to total bilirubin to confirm the diagnosis 1
• Considering other causes of unconjugated hyperbilirubinemia, such as hemolysis or multiple transfusions 1
• Evaluating patients with elevated conjugated bilirubin for other liver conditions, such as viral hepatitis or obstructive biliary disease 1
• Using genetic testing for DNA mutations of uridine 5'-diphospho-glucuronyl-transferase to confirm the diagnosis of Gilbert's syndrome 1

Overall, the evidence suggests that conjugated bilirubin is not typically increased in Gilbert's syndrome, and that other liver conditions should be suspected if conjugated bilirubin is elevated.

From the Research

Conjugated Bilirubin in Gilbert's Syndrome

• The level of conjugated bilirubin in Gilbert's syndrome is a topic of interest in various studies 2, 3, 4, 5, 6.
• According to a study published in the Journal of Hepatology, the administration of rifampicin increased the relative amounts of conjugated serum bilirubin in patients with Gilbert's syndrome 2.
• However, another study published in Clinica Chimica Acta found that the relative proportion of unconjugated bilirubin in serum was higher in patients with Gilbert's syndrome compared to healthy subjects, with unconjugated bilirubin ranging between 90 and 99% of total bilirubin in Gilbert's syndrome 3.
• A study published in Gastroenterology found that the concentration of total conjugates was comparable to the values in healthy control subjects in Gilbert's syndrome, but the fraction of conjugated relative to total bilirubins was markedly decreased due to the increased concentration of unconjugated pigment 6.

Key Findings

• The studies suggest that while the absolute level of conjugated bilirubin may not be increased in Gilbert's syndrome, the proportion of conjugated bilirubin relative to total bilirubin is decreased due to the increased level of unconjugated bilirubin 3, 6.
• The use of rifampicin can increase the level of conjugated bilirubin in patients with Gilbert's syndrome, which may be useful for diagnostic purposes 2, 5.
• The pattern of serum bilirubins, including the levels of conjugated and unconjugated bilirubin, can be useful in the diagnosis and differential diagnosis of unconjugated hyperbilirubinemia 6.