What is the diagnostic workup for jaundice (hyperbilirubinemia)?

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From the Guidelines

The workup for jaundice should begin with a thorough history and physical examination, followed by laboratory tests including complete blood count, liver function tests (bilirubin, ALT, AST, alkaline phosphatase, GGT), coagulation studies, and hepatitis serologies, as recommended by the American College of Radiology Appropriateness Criteria 1.

Initial Evaluation

The initial evaluation of a patient with jaundice should include a detailed history, targeted physical examination, and pertinent laboratory studies to categorize the type of jaundice into mechanical or nonmechanical causes 1.

  • Laboratory tests should include:
    • Complete blood count
    • Liver function tests (bilirubin, ALT, AST, alkaline phosphatase, GGT)
    • Coagulation studies
    • Hepatitis serologies

Imaging Studies

Initial imaging typically includes an abdominal ultrasound to evaluate the liver, biliary tree, and pancreas, looking for obstruction, masses, or parenchymal disease 1.

  • If obstruction is suspected, further imaging with MRCP (magnetic resonance cholangiopancreatography) or ERCP (endoscopic retrograde cholangiopancreatography) may be necessary 1.

Additional Tests

For suspected hepatocellular causes, additional tests might include:

  • Autoimmune markers
  • Iron studies
  • Ceruloplasmin levels
  • Alpha-1 antitrypsin levels In cases of hemolysis, a peripheral blood smear, reticulocyte count, and Coombs test should be ordered 1.

Urgent Evaluation

Urgent evaluation is warranted for patients with signs of acute liver failure, such as encephalopathy or coagulopathy, or cholangitis, characterized by fever, right upper quadrant pain, and jaundice (Charcot's triad) 1.

From the Research

Initial Evaluation

The work-up for jaundice typically begins with a comprehensive medical history, review of systems, and physical examination to differentiate potential causes 2, 3, 4, 5. This initial evaluation is crucial in guiding further laboratory tests and imaging studies.

Laboratory Tests

Initial laboratory evaluation should include:

  • Assays for bilirubin (total and fractionated) to determine whether the hyperbilirubinemia is conjugated or unconjugated 2, 5
  • Complete blood cell count 2, 5
  • Liver function tests, such as aspartate transaminase, alanine transaminase, gamma-glutamyltransferase, and alkaline phosphatase 2, 5
  • Albumin and prothrombin time/international normalized ratio to assess liver function and coagulation 2, 5

Imaging Studies

Imaging studies, such as:

  • Ultrasonography of the abdomen 2, 3, 5
  • Computed tomography with intravenous contrast media 2, 3
  • Magnetic resonance cholangiopancreatography 2 are used to differentiate between extrahepatic obstructive and intrahepatic parenchymal disorders.

Further Evaluation

If the etiology of jaundice is unclear despite laboratory testing and imaging, further evaluation may include:

  • Liver biopsy to establish the diagnosis, prognosis, and management of the disease 2
  • Additional cancer screening, biliary imaging, autoimmune antibody assays 5
  • Referral to a specialist when likelihood of malignancy, chronic autoimmune condition, or need for intervention exists 4

Classification of Hyperbilirubinemia

Hyperbilirubinemia can be categorized into:

  • Unconjugated/prehepatic causes, such as hemolysis and disorders of impaired bilirubin conjugation 3, 5
  • Intrahepatic causes, such as hepatocellular damage and cholestatic disorders 3, 5
  • Posthepatic/obstructive causes, such as gallstone formation and malignancies 3, 5

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Evaluation of Jaundice in Adults.

American family physician, 2025

Research

Jaundice in the adult patient.

American family physician, 2004

Research

Evaluation of Jaundice in Adults.

American family physician, 2017

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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