What are the laboratory findings in Gilbert's syndrome (a benign condition characterized by elevated bilirubin levels)?

From the Guidelines

Gilbert syndrome is diagnosed through blood tests showing elevated unconjugated (indirect) bilirubin levels, with the proportion of conjugated bilirubin being less than 20%-30% of the total bilirubin, as recommended by the consensus guidelines 1. The key laboratory finding is isolated hyperbilirubinemia without evidence of hemolysis or liver disease.

• Complete liver function tests should be performed, including total and direct bilirubin, ALT, AST, alkaline phosphatase, and GGT, all of which should be normal except for the elevated unconjugated bilirubin.
• A complete blood count should also be normal, ruling out hemolytic anemia.
• Genetic testing for UGT1A1 gene mutations (particularly the UGT1A1*28 variant) can confirm the diagnosis but is rarely necessary for clinical management, as stated in the guidelines 1. Bilirubin levels may fluctuate and increase during fasting, illness, or stress. No treatment is required for Gilbert syndrome as it's a benign condition, though patients should be aware that certain medications metabolized by the UGT1A1 enzyme (like irinotecan) may require dose adjustments, as noted in the study 1. The condition results from reduced activity of the enzyme UDP-glucuronosyltransferase, which is responsible for conjugating bilirubin for excretion. 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, as highlighted in the study 1.

From the Research

Laboratory Findings in Gilbert Syndrome

• Total serum bilirubin concentrations are often elevated, with minimal values at 1.57 +/- 0.56 mg/dl and maximal values at 2.05 +/- 0.65 mg/dl 2
• Unconjugated hyperbilirubinemia is a characteristic feature of Gilbert syndrome, with mildly elevated total bilirubin and normal serum activities of liver transaminases, biliary damage markers, and red blood cell counts 3
• Liver function studies, such as galactose elimination capacity, aminopyrine breath test, or fasting and postprandial serum bile acids, are typically within normal limits 2
• Hematological investigations, including hemoglobin electrophoresis, Coombs tests, and erythrocyte enzymes, usually yield normal results, although osmotic fragility may be increased and erythrocyte survival reduced in some cases 2

Diagnostic Tests for Gilbert Syndrome

• Nicotinic acid test: total serum bilirubin rises within 3 hours, with retention values exceeding 70% after 5 hours corresponding to bilirubin clearances of less than 20 ml/min 2
• Rifampicin test and caloric restriction test: two non-invasive diagnostic means that can be used to assure the diagnosis of Gilbert's syndrome, avoiding the need for liver biopsy 4
• Assessment of bilirubin concentrations as part of routine liver function testing can also indicate the presence of Gilbert's syndrome, particularly in cases with mildly elevated unconjugated bilirubin and normal liver enzymes 3