Liver Enzymes in Gilbert Syndrome
No, liver enzymes (ALT, AST, alkaline phosphatase, and GGT) remain normal in Gilbert syndrome—this is a defining diagnostic feature that distinguishes it from hepatocellular disease. 1
Diagnostic Laboratory Profile
Gilbert syndrome presents with a characteristic pattern that specifically excludes liver enzyme elevation:
- ALT and AST are normal in all cases of Gilbert syndrome 1
- Alkaline phosphatase and GGT remain normal throughout the disease course 1
- All other liver function tests are normal, including albumin and prothrombin time 1
The only laboratory abnormality is mild unconjugated hyperbilirubinemia, typically 1.5-3 mg/dL, rarely exceeding 4-5 mg/dL 1, 2
Critical Diagnostic Criteria
The bilirubin pattern is pathognomonic:
- Unconjugated (indirect) bilirubin comprises >70-80% of total bilirubin 1
- Conjugated bilirubin must be <20-30% of total bilirubin to confirm the diagnosis 1, 2
- Complete blood count is normal, excluding hemolysis 1
Clinical Significance and Pitfalls
If liver enzymes are elevated, the diagnosis is NOT Gilbert syndrome—you must pursue alternative diagnoses including:
- Viral hepatitis (typically presents with AST/ALT >400 IU/mL) 2
- Drug-induced liver injury (elevated transaminases with different bilirubin pattern) 2
- Autoimmune hepatitis or other hepatocellular disease 2
Common diagnostic error: The terms "direct" and "conjugated" bilirubin are often incorrectly used interchangeably. Direct bilirubin includes both conjugated bilirubin AND delta bilirubin (albumin-bound with 21-day half-life), which can falsely suggest liver disease 1, 2. Always specifically request conjugated bilirubin fraction for accurate diagnosis 1.
Epidemiology and Clinical Context
Gilbert syndrome affects 5-10% of the population, with males predominating approximately 5:1 1, 2. Accurate identification is crucial to avoid:
- Unnecessary diagnostic testing 3
- Incorrect attribution to drug-induced liver injury in clinical trials 3
- Unwarranted drug interruption or discontinuation 3
The presence of ANY liver enzyme elevation should prompt immediate investigation for alternative hepatobiliary pathology rather than attributing findings to Gilbert syndrome 4, 1.