What are the typical lab findings in Gilbert's syndrome (a benign genetic disorder characterized by mildly elevated levels of unconjugated bilirubin)?

From the Guidelines

Gilbert syndrome is characterized by elevated unconjugated (indirect) bilirubin levels in the blood, typically between 1-3 mg/dL, with normal liver function tests, as confirmed by a recent study 1. The key laboratory finding is mild hyperbilirubinemia without evidence of hemolysis or liver damage.

• Liver enzymes such as ALT, AST, and alkaline phosphatase remain within normal ranges.
• Complete blood count is normal with no signs of anemia or increased red blood cell turnover. The diagnosis is often made incidentally during routine blood tests and can be confirmed when bilirubin levels increase during fasting, illness, or physical exertion.
• Genetic testing may reveal a mutation in the UGT1A1 gene, specifically the UGT1A1*28 variant, which reduces the activity of the enzyme responsible for bilirubin conjugation by about 30%, as noted in 1 and 1. This hereditary condition affects approximately 5-10% of the population and is more common in males, as reported in 1 and 1. No treatment is necessary as Gilbert syndrome is benign and does not lead to liver damage or other health complications, as supported by the most recent evidence 1.

From the Research

Lab Findings in Gilbert Syndrome

• Mildly elevated total bilirubin with normal serum activities of liver transaminases, biliary damage markers, and red blood cell counts may indicate the presence of Gilbert's syndrome (GS) 2
• The fraction of plasma unconjugated bilirubin of total bilirubin was significantly different in patients with Gilbert's syndrome, acute hepatitis, and normal subjects 3
• Analysis of serum unconjugated and conjugated bilirubin fractions by routine diazo procedures does not allow a definite diagnosis of Gilbert's syndrome, but the alkaline methanolysis procedure followed by thin-layer chromatography can discriminate Gilbert's syndrome even in the presence of normal serum bilirubin concentrations 4
• The relative proportion of unconjugated bilirubin in serum was 95 +/- 2% in patients with Gilbert's syndrome, which is significantly higher than in healthy subjects, patients with chronic persistent hepatitis, and patients with chronic hemolysis 4
• The overnight rifampin test can be used as a diagnostic test for Gilbert's syndrome, with elevation of total serum bilirubin after rifampin above 2.4 mg/dL being 93.8% sensitive and 93.3% specific for the diagnosis of GS, and elevation of unconjugated bilirubin above 1.3 mg/dL being 100% sensitive and 100% specific 5

Diagnostic Criteria

• Mild hyperbilirubinemia with a high fraction of unconjugated bilirubin, normal values of liver enzymes, and no overt signs of hemolysis can establish a clinical diagnosis of Gilbert's syndrome with relative certainty 3
• The caloric restriction and phenobarbital stimulation tests have low diagnostic specificity in Gilbert's syndrome when the differential diagnosis is that of hepatitis 3
• Phenobarbital treatment can improve the clearance of unconjugated bilirubin from plasma and increase serum gamma-glutamyltranspeptidase activity and urinary d-glucaric acid excretion in patients with Gilbert's syndrome 6

Biochemical Markers

• Unconjugated bilirubin is the primary biochemical marker for Gilbert's syndrome, with levels ranging from 90 to 99% of total bilirubin in patients with the condition 4
• Serum total and unconjugated bilirubin levels can be measured before and after rifampin administration to aid in the diagnosis of Gilbert's syndrome 5