What is the approach for evaluating jaundice?

Approach to Evaluating Jaundice

The initial evaluation of jaundice should begin with laboratory testing to differentiate between unconjugated (nonobstructive) and conjugated (obstructive) hyperbilirubinemia, followed by abdominal ultrasound as the first-line imaging study for suspected biliary obstruction. 1

Initial Clinical Assessment

• Jaundice becomes clinically apparent when serum bilirubin levels exceed 2.5-3 mg/dL, manifesting as yellowing of the skin and sclera 2, 3
• The most common causes of jaundice in the United States are: hepatitis/sepsis, alcoholic liver disease, common bile duct (CBD) obstruction by stones or tumor, and toxic reactions to drugs or herbs 1
• Targeted history should focus on alcohol use, medication/herbal supplement intake, risk factors for viral hepatitis, and symptoms of biliary obstruction (right upper quadrant pain, dark urine, clay-colored stools) 2, 4
• Physical examination should assess for signs of chronic liver disease (spider angiomata, palmar erythema, ascites), hepatomegaly, and right upper quadrant tenderness 4, 3

Laboratory Evaluation

• Initial laboratory testing must include 1, 2:

  • Total and fractionated (direct/conjugated) bilirubin
  • Complete blood count
  • Liver enzymes: AST, ALT (hepatocellular injury)
  • Alkaline phosphatase, gamma-glutamyltransferase (cholestasis)
  • Albumin, prothrombin time, INR (liver synthetic function)

• Categorization based on laboratory findings 1, 4:

  • Unconjugated (nonobstructive) hyperbilirubinemia: hepatitis, sepsis, alcoholic liver disease, drug-induced liver disease
  • Conjugated (obstructive) hyperbilirubinemia: CBD obstruction by stones or tumor

Imaging Studies

• Abdominal ultrasound is the recommended initial imaging study for jaundiced patients 1:

  • High sensitivity (65-95%) for detecting cirrhosis with 98% positive predictive value 1
  • Variable sensitivity (32-100%) and specificity (71-97%) for biliary obstruction 1
  • Can detect dilated intrahepatic/extrahepatic bile ducts 1
  • Limited sensitivity (22.5-75%) for CBD stone detection due to overlying bowel gas 1
  • Recommended by the American College of Gastroenterology as the initial diagnostic test for suspected CBD obstruction 1

• Additional imaging based on ultrasound findings and clinical suspicion 2, 4:

  • CT with IV contrast: better evaluation of liver parenchyma and potential masses
  • MRCP: superior for detailed biliary tract imaging when obstruction is suspected
  • ERCP: diagnostic and therapeutic for biliary obstruction

Diagnostic Algorithm

1. Obtain fractionated bilirubin, liver enzymes, and synthetic function tests 1, 2

2. If predominantly unconjugated hyperbilirubinemia:

   • Evaluate for hemolysis, Gilbert syndrome, or drug effects 1, 5
   • Consider viral hepatitis serologies if transaminases elevated 2, 3

3. If predominantly conjugated hyperbilirubinemia:

   • Perform abdominal ultrasound to assess for biliary dilation and liver parenchyma 1
   • If bile ducts dilated: proceed to MRCP or ERCP for further evaluation and potential intervention 2, 4
   • If bile ducts normal: consider intrahepatic cholestasis, drug-induced liver injury, or infiltrative diseases 4, 5

4. If diagnosis remains unclear after laboratory testing and imaging, liver biopsy may be required 2, 3

Special Considerations

• Jaundice persisting beyond 3 weeks requires measurement of total and direct bilirubin to identify cholestasis 1
• Sensitivity of CBD stone detection on ultrasound can be increased to 70-86% by combining tissue harmonic imaging with findings of elevated bilirubin, patient age >55 years, and CBD dilation between 6-10 mm 1
• A normal CBD caliber on ultrasound has a 95-96% negative predictive value for choledocholithiasis in patients with symptomatic gallstones 1
• Multiple small (<5 mm) gallstones in the gallbladder create a 4-fold risk for migration into the CBD 1