What is the workup for a patient with hyperbilirubinemia (elevated bilirubin levels) with a conjugated fraction greater than 20%?

From the Guidelines

The workup for a patient with hyperbilirubinemia with a conjugated fraction greater than 20% should start with a comprehensive history and physical examination, followed by laboratory tests including complete liver function tests, and imaging studies such as abdominal ultrasound, as recommended by the most recent guidelines 1. The initial evaluation should focus on identifying the underlying cause of cholestasis or hepatocellular injury.

• Laboratory tests should include:
  • Complete liver function tests (ALT, AST, alkaline phosphatase, GGT)
  • Complete blood count
  • Coagulation studies (PT/INR)
  • Serology for viral hepatitis (hepatitis A, B, C, E)
• Imaging studies are essential, starting with an abdominal ultrasound to assess for biliary obstruction, gallstones, or liver parenchymal abnormalities. Depending on initial findings, additional imaging such as MRCP, ERCP, or CT may be indicated, as suggested by the American College of Radiology 1. If no obstruction is found, further testing should include:
• Autoimmune markers (ANA, ASMA, AMA)
• Ceruloplasmin for Wilson's disease
• Alpha-1 antitrypsin levels
• Iron studies In cases without a clear diagnosis after non-invasive testing, liver biopsy may be necessary, as recommended by consensus guidelines 1. This systematic approach is important because conjugated hyperbilirubinemia indicates impaired bile excretion or hepatocellular damage and often represents significant underlying pathology requiring prompt diagnosis and management to prevent progression of liver disease.

From the Research

Workup for Hyperbilirubinemia with Conjugated Fraction Greater than 20%

The workup for a patient with hyperbilirubinemia and a conjugated fraction greater than 20% involves a comprehensive approach to determine the underlying cause of the elevated bilirubin levels.

• Initial laboratory evaluation should include:
  • Bilirubin (total and fractionated) to confirm the presence of conjugated hyperbilirubinemia 2
  • Complete blood cell count to rule out hemolysis
  • Liver function tests, such as aspartate transaminase, alanine transaminase, gamma-glutamyltransferase, and alkaline phosphatase, to assess liver damage or dysfunction
  • Albumin and prothrombin time to evaluate hepatic synthetic function
• Imaging studies, such as:
  • Ultrasonography of the abdomen to evaluate the liver, gallbladder, and biliary tract
  • Computed tomography with intravenous contrast media or magnetic resonance cholangiopancreatography to further assess the liver and biliary system 2, 3
• A thorough medical history and physical examination to identify potential causes of hyperbilirubinemia, such as:
  • Alcoholic liver disease 4
  • Biliary strictures or obstruction
  • Choledocholithiasis
  • Drug-induced liver injury
  • Hemolysis
  • Hepatitis
  • Antiviral therapy-related hyperbilirubinemia 5

Additional Diagnostic Considerations

• If the etiology of jaundice is unclear despite laboratory testing and imaging, liver biopsy may be required to establish the diagnosis, prognosis, and management of the disease 2
• A stepwise approach to evaluation can help elucidate the underlying mechanism of disease and guide treatment decisions 3