From the Guidelines
For chronic elevated bilirubin, the recommended laboratory workup includes a comprehensive metabolic panel with liver function tests, direct and indirect bilirubin fractionation, and specific tests such as hepatitis serologies and autoimmune markers, as the most recent and highest quality study suggests a thorough evaluation to determine the underlying cause of hyperbilirubinemia 1. The evaluation should start with a comprehensive metabolic panel to assess liver function, including AST, ALT, alkaline phosphatase, and GGT, as well as a complete blood count to rule out hemolysis or other hematological disorders.
- Direct and indirect bilirubin fractionation is essential to determine the type of hyperbilirubinemia and guide further testing.
- Additional specific tests may include:
- Hepatitis serologies (A, B, C) to evaluate for viral hepatitis
- Autoimmune markers (ANA, anti-smooth muscle antibody, anti-mitochondrial antibody) to assess for autoimmune liver disease
- Iron studies (ferritin, transferrin saturation) to evaluate for iron overload or deficiency
- Ceruloplasmin for Wilson's disease
- Alpha-1 antitrypsin levels to assess for alpha-1 antitrypsin deficiency
- Hemolysis evaluation with reticulocyte count, haptoglobin, and LDH should be performed if indirect hyperbilirubinemia is present to rule out hemolytic anemia.
- Genetic testing for conditions like Gilbert's syndrome or Dubin-Johnson syndrome may be warranted in certain cases.
- Abdominal ultrasound is also important to assess liver structure and rule out biliary obstruction, as recommended by the most recent consensus guidelines 1. This comprehensive approach helps differentiate between hepatocellular, cholestatic, or hemolytic causes of hyperbilirubinemia, allowing for appropriate management of the underlying condition causing the chronic bilirubin elevation.
From the Research
Laboratory Evaluation for Chronic Elevated Bilirubin
The following laboratory tests are recommended for the evaluation of chronic elevated bilirubin:
- Bilirubin (total and fractionated) to determine whether the hyperbilirubinemia is conjugated or unconjugated 2, 3, 4
- Complete blood cell count to evaluate for hemolysis or other blood disorders 2, 3, 5
- Alanine transaminase and aspartate transaminase to assess liver damage 2, 3, 4, 5
- Alkaline phosphatase to evaluate for cholestatic disease 2, 3, 4, 5
- Gamma-glutamyltransferase to assess liver damage 2
- Albumin and prothrombin time to evaluate liver function 2, 5
- International normalized ratio to assess coagulation status 2
Additional Tests
Additional tests may be ordered based on the patient's specific risk factors and the pattern of abnormal liver test results, including:
- Hepatitis B surface antigen and hepatitis C antibody to evaluate for viral hepatitis 4, 5
- Ferritin and iron levels and transferrin saturation to evaluate for hereditary hemochromatosis 4, 5
- Autoimmune antibody assays to evaluate for autoimmune hepatitis 4
- Right upper quadrant abdominal ultrasonography to evaluate the liver and biliary tract 2, 3, 5
- Liver biopsy may be considered when serologic testing and imaging fail to elucidate a diagnosis, to stage a condition, or when multiple diagnoses are possible 2, 4