From the Guidelines
For elevated direct bilirubin, the next laboratory tests should include a comprehensive hepatic panel with ALT, AST, alkaline phosphatase, GGT, total protein, albumin, and PT/INR to assess liver function, as recommended by the most recent guidelines 1. The comprehensive hepatic panel will help differentiate between hepatocellular damage, cholestasis, and biliary obstruction as causes of elevated direct bilirubin. Additional tests should include:
- A complete blood count to evaluate for hemolysis
- Hepatitis serologies (A, B, C) to assess for viral hepatitis
- Autoimmune markers (ANA, anti-smooth muscle antibody, anti-mitochondrial antibody) to evaluate for autoimmune hepatitis
- Abdominal imaging such as ultrasound or CT scan to assess for biliary obstruction or other liver pathology If obstruction is suspected, MRCP or ERCP may be necessary to further evaluate the biliary system. Direct (conjugated) hyperbilirubinemia typically indicates that the liver is able to conjugate bilirubin but cannot excrete it properly, suggesting either hepatocellular dysfunction or biliary obstruction, as noted in the guidelines 1. Depending on the clinical context, additional specialized tests may include:
- Iron studies to evaluate for hemochromatosis
- Ceruloplasmin levels for Wilson's disease
- Alpha-1 antitrypsin levels to assess for alpha-1 antitrypsin deficiency
- Tests for primary biliary cholangitis to evaluate for autoimmune liver disease Prompt evaluation is important as elevated direct bilirubin often indicates significant liver pathology requiring timely intervention, as emphasized in the guidelines 1.
From the Research
Next Lab Tests for Elevated Direct Bilirubin
- To further evaluate elevated direct bilirubin, the following lab tests may be considered:
- Fractionation of total bilirubin to direct and indirect bilirubin fractions 2
- Testing for viral hepatitis A, B, and C 2
- Assessment for nonalcoholic fatty liver disease and alcoholic liver disease 2
- Screening for hereditary hemochromatosis, autoimmune hepatitis, Wilson's disease, and alpha-1 antitrypsin deficiency 2
- For cases where the alkaline phosphatase elevation is determined to be of hepatic origin, additional tests may include:
- Testing for primary biliary cholangitis and primary sclerosing cholangitis 2
- A 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
Rationale for Testing
- Elevated conjugated bilirubin implies hepatocellular disease or biliary obstruction in most settings 2
- The degree of elevation of ALT and/or AST in the clinical setting helps guide the evaluation 2
- A true healthy normal ALT level ranges from 29 to 33 IU/l for males, 19 to 25 IU/l for females, and levels above this should be assessed 2