From the Guidelines
Laboratory tests for elevated bilirubin should include a comprehensive panel to determine the cause and severity of hyperbilirubinemia, starting with a total bilirubin level, direct and indirect bilirubin fractions, liver function tests (ALT, AST, alkaline phosphatase, and GGT), and a complete blood count, as recommended by the most recent guidelines 1.
Initial Evaluation
The initial evaluation should determine whether the hyperbilirubinemia is conjugated (direct) or unconjugated (indirect) to differentiate between various types of jaundice.
- Unconjugated hyperbilirubinemia may suggest hemolysis, Gilbert's syndrome, or other pre-hepatic causes.
- Conjugated hyperbilirubinemia may indicate liver disease, biliary obstruction, or post-hepatic causes.
Additional Tests
Additional tests may include:
- Hepatitis serologies to detect viral infections
- Abdominal ultrasound to visualize the liver and biliary tract
- MRCP or ERCP for detailed imaging of bile ducts
- Liver biopsy for definitive diagnosis in complex cases
Diagnostic Approach
The diagnostic approach should be guided by the clinical scenario, with consideration of the patient's symptoms, laboratory values, and imaging findings.
- In asymptomatic patients with mild laboratory abnormalities, a reasonable approach may include an initial evaluation for common hepatic diseases, with close clinical follow-up if the initial studies are unrevealing.
- In patients with significant symptoms, evidence of chronic or decompensated liver disease, or severe liver chemistry abnormalities, a complete and expeditious evaluation is essential, as recommended by 1.
Recent Guidelines
Recent guidelines from the American College of Radiology 1 emphasize the importance of a comprehensive diagnostic approach, including laboratory tests, imaging studies, and liver biopsy, to determine the cause and severity of hyperbilirubinemia.
- The guidelines recommend a step-wise approach, starting with non-invasive tests and progressing to more invasive procedures as needed.
- The choice of diagnostic tests should be guided by the clinical scenario and the results of initial evaluations, as suggested by 1 and 1.
From the Research
Laboratory Evaluation for Elevated Bilirubin
The initial laboratory evaluation for elevated bilirubin levels should include:
- Fractionated bilirubin to determine whether the hyperbilirubinemia is conjugated or unconjugated 2, 3
- Complete blood count 2, 3
- Alanine transaminase and aspartate transaminase to assess liver damage 2, 3
- Alkaline phosphatase and ?-glutamyltransferase to evaluate cholestasis 2
- Prothrombin time and/or international normalized ratio to assess coagulation 2, 3
- Albumin and protein levels to evaluate liver function 2, 3
Measurement of Bilirubin
Bilirubin can be measured using various analytical methods, including:
- Diazo transfer reaction, currently the gold-standard 4
- High-performance liquid chromatography (HPLC) 4
- Oxidative, enzymatic, and chemical methods 4
- Direct spectrophotometry 4
- Transcutaneous methods 4
Clinical Significance of Bilirubin
Elevated bilirubin levels can indicate underlying liver disease or biliary tract disorders 2, 3, 5, 6