What are the initial tests for diagnosing jaundice?

Testing for Jaundice: Initial Diagnostic Approach

The initial tests for diagnosing jaundice should include liver function tests with fractionated bilirubin (total, direct/conjugated, and indirect/unconjugated), complete blood count, liver enzymes (ALT, AST, alkaline phosphatase), and abdominal ultrasound. 1, 2

Laboratory Evaluation

First-line Laboratory Tests

• Bilirubin measurements:
  • Total bilirubin
  • Direct (conjugated) bilirubin
  • Indirect (unconjugated) bilirubin
• Liver enzymes:
  • Alanine aminotransferase (ALT)
  • Aspartate aminotransferase (AST)
  • Alkaline phosphatase
  • Gamma-glutamyltransferase (GGT)
• Synthetic function assessment:
  • Albumin
  • Prothrombin time (PT)
  • International normalized ratio (INR)
• Complete blood count (CBC) with platelet count 1, 2, 3

Pattern Recognition

The pattern of laboratory abnormalities helps categorize the cause of jaundice:

1. Predominantly unconjugated hyperbilirubinemia:

   • Suggests hemolysis, Gilbert's syndrome, or other pre-hepatic causes
   • Typically normal liver enzymes

2. Predominantly conjugated hyperbilirubinemia with elevated alkaline phosphatase:

   • Suggests cholestatic or obstructive jaundice
   • May indicate gallstones, biliary strictures, or malignancy

3. Elevated transaminases (ALT/AST) with jaundice:

   • Suggests hepatocellular injury
   • May indicate viral hepatitis, drug-induced liver injury, or alcoholic hepatitis 1, 2

Imaging Studies

First-line Imaging

• Abdominal ultrasound: The initial imaging modality of choice for jaundice
  • Sensitivity: 84.8%, Specificity: 93.6%
  • Evaluates for:
    • Biliary dilation
    • Gallstones
    • Liver parenchymal abnormalities
    • Masses or lesions 1, 2

Second-line Imaging (based on initial findings)

• Computed tomography (CT) with IV contrast:

  • When ultrasound is inconclusive or malignancy is suspected
  • Better visualization of the pancreas and retroperitoneum

• Magnetic resonance cholangiopancreatography (MRCP):

  • Non-invasive evaluation of biliary and pancreatic ducts
  • Particularly useful for suspected biliary obstruction when ultrasound is inconclusive 1, 3

Diagnostic Algorithm

1. Determine if jaundice is conjugated or unconjugated:

   • Urine bilirubin test: Positive indicates conjugated hyperbilirubinemia 1, 4

2. For unconjugated hyperbilirubinemia:

   • Evaluate for hemolysis (CBC, reticulocyte count, haptoglobin)
   • Consider Gilbert's syndrome if mild elevation and other tests normal

3. For conjugated hyperbilirubinemia:

   • Perform abdominal ultrasound to assess for biliary obstruction
   • If no obstruction evident, evaluate for:
     • Viral hepatitis (HAV IgM, HBsAg, HBcAb IgM, HCV antibody)
     • Autoimmune hepatitis (ANA, ASMA, immunoglobulins)
     • Drug-induced liver injury (medication history)
     • Alcoholic liver disease (history, AST:ALT ratio >2)
     • Wilson disease in young patients (ceruloplasmin, 24-hour urinary copper) 1, 2

4. If biliary obstruction is present on imaging:

   • Further evaluate with MRCP or CT
   • Consider ERCP or endoscopic ultrasound for therapeutic intervention or tissue sampling 1

Special Considerations

• Low alkaline phosphatase with jaundice: Consider Wilson disease, especially in patients under 40 years 1, 2
• AST:ALT ratio >2: Suggests alcoholic liver disease or Wilson disease 2
• Persistent abnormal liver tests: Warrant further investigation as 84% of abnormal liver tests remain abnormal after 1 month 2
• Family screening: First-degree relatives of patients with Wilson disease should be screened with serum copper, ceruloplasmin, liver function tests, and eye examination for Kayser-Fleischer rings 1

Common Pitfalls to Avoid

• Assuming mild elevations are benign: Even mild liver test abnormalities can indicate significant underlying disease 2
• Incomplete bilirubin fractionation: Failing to differentiate between conjugated and unconjugated hyperbilirubinemia can lead to diagnostic errors
• Relying solely on laboratory tests: Imaging is essential for complete evaluation of jaundice
• Overlooking medication history: Many drugs can cause jaundice through various mechanisms 2, 3
• Delaying evaluation in severe cases: Patients with signs of hepatic decompensation (coagulopathy, encephalopathy) require expedited evaluation 1