What is the workup for elevated bilirubin (hyperbilirubinemia)?

From the Guidelines

The workup for elevated bilirubin (hyperbilirubinemia) should begin with determining whether the elevation is predominantly unconjugated (indirect) or conjugated (direct) bilirubin, as this guides further investigation. Initial testing should include a complete blood count, liver function tests (AST, ALT, alkaline phosphatase, GGT), and fractionated bilirubin levels. For predominantly unconjugated hyperbilirubinemia, evaluation should focus on hemolysis (reticulocyte count, haptoglobin, LDH, peripheral blood smear) or genetic disorders like Gilbert's syndrome 1. For conjugated hyperbilirubinemia, further workup includes abdominal ultrasound to assess for biliary obstruction, viral hepatitis serologies (hepatitis A, B, C), autoimmune markers (ANA, anti-smooth muscle antibody, anti-mitochondrial antibody), and assessment for medication-induced liver injury 1. Additional testing may include MRCP or ERCP for suspected biliary obstruction, liver biopsy for parenchymal disease, or genetic testing for hereditary conditions like Dubin-Johnson or Rotor syndrome. The pattern of liver enzyme elevation provides important clues - cholestatic patterns (elevated alkaline phosphatase and GGT) suggest biliary obstruction, while hepatocellular patterns (elevated AST and ALT) suggest hepatocyte injury 1. Prompt diagnosis is essential as some causes require urgent intervention, particularly obstructive jaundice which may necessitate biliary decompression to prevent complications like cholangitis.

Some key points to consider in the workup of hyperbilirubinemia include:

• The distinction between unconjugated and conjugated hyperbilirubinemia is crucial, as it guides further investigation and management 1.
• Abdominal ultrasound is a useful initial imaging test for assessing biliary obstruction 1.
• Viral hepatitis serologies and autoimmune markers should be considered in the workup of conjugated hyperbilirubinemia 1.
• Genetic testing may be necessary for hereditary conditions like Dubin-Johnson or Rotor syndrome 1.
• Prompt diagnosis and management are essential to prevent complications like cholangitis in obstructive jaundice 1.

Overall, a systematic approach to the workup of hyperbilirubinemia, guided by the distinction between unconjugated and conjugated hyperbilirubinemia, is essential for prompt diagnosis and management of underlying causes.

From the Research

Workup for Elevated Bilirubin

The workup for elevated bilirubin (hyperbilirubinemia) involves a series of tests to determine the underlying cause of the condition. The approach to evaluating a patient with jaundice, which is a physical finding associated with hyperbilirubinemia, typically starts with a careful history and physical examination, followed by laboratory tests and imaging studies.

Initial Laboratory Evaluation

The initial laboratory evaluation should include:

• Fractionated bilirubin to distinguish between unconjugated and conjugated hyperbilirubinemia 2
• Complete blood count to evaluate for hemolytic disorders
• Liver function tests, such as alanine transaminase, aspartate transaminase, alkaline phosphatase, and γ-glutamyltransferase, to assess liver damage or disease
• Prothrombin time and/or international normalized ratio to evaluate coagulation
• Albumin and protein levels to assess liver synthetic function

Imaging Studies

Imaging studies, such as ultrasonography or computed tomography, can help differentiate between extrahepatic obstructive and intrahepatic parenchymal disorders 2, 3. Ultrasonography is the least invasive and least expensive imaging method.

Additional Tests

Additional tests may be necessary to evaluate the underlying cause of hyperbilirubinemia, including:

• Autoimmune antibody assays to evaluate for autoimmune liver disease
• Biliary imaging to evaluate the biliary tree
• Liver biopsy to evaluate liver histology
• Cancer screening to evaluate for hepatobiliary malignancy

Causes of Hyperbilirubinemia

Hyperbilirubinemia can be caused by a variety of conditions, including:

• Hemolytic disorders, such as hemolytic anemia 4
• Disorders of impaired bilirubin conjugation, such as Gilbert's syndrome 5
• Hepatocellular damage, such as viral and alcoholic hepatitis
• Cholestatic disorders, such as choledocholithiasis and neoplastic obstruction of the biliary tree
• Antiviral therapy, which can cause hyperbilirubinemia as a side effect 6

Approach to Evaluation

The approach to evaluating a patient with hyperbilirubinemia should be tailored to the individual patient's presentation and laboratory results. A careful history and physical examination, followed by directed laboratory tests and imaging studies, can help determine the underlying cause of the condition and guide further management 2, 3.