From the Guidelines
The workup for elevated bilirubin should begin with a thorough history and physical examination, followed by laboratory tests to determine if the hyperbilirubinemia is unconjugated (indirect) or conjugated (direct) 1. Initial tests should include complete blood count, liver function tests (ALT, AST, alkaline phosphatase, GGT), direct and indirect bilirubin levels, and a complete metabolic panel. For unconjugated hyperbilirubinemia, evaluate for hemolysis with reticulocyte count, haptoglobin, LDH, and peripheral blood smear. Consider genetic testing for conditions like Gilbert's syndrome if other causes are ruled out 1. For conjugated hyperbilirubinemia, ultrasound of the liver and biliary system is essential to assess for obstruction 1. Additional imaging may include CT scan, MRCP, or ERCP depending on initial findings. If biliary obstruction is identified, intervention may be needed via ERCP or surgery. For parenchymal liver disease, consider viral hepatitis serologies, autoimmune markers (ANA, anti-smooth muscle antibody), iron studies, ceruloplasmin (Wilson's disease), alpha-1 antitrypsin levels, and potentially liver biopsy. The specific workup pathway depends on whether the elevation is predominantly direct or indirect bilirubin, as this distinction helps narrow down potential causes between hepatocellular damage, biliary obstruction, or increased bilirubin production from hemolysis. Key considerations in the workup include:
- Differentiating between unconjugated and conjugated hyperbilirubinemia to guide further testing and management
- Evaluating for hemolysis in cases of unconjugated hyperbilirubinemia
- Assessing for biliary obstruction in cases of conjugated hyperbilirubinemia
- Considering genetic testing for conditions like Gilbert's syndrome
- Utilizing imaging studies such as ultrasound, CT, MRCP, or ERCP as needed to evaluate the liver and biliary system.
From the Research
Elevated Bilirubin Workup
Elevated bilirubin levels can indicate an underlying disease state, and a thorough workup is necessary to determine the cause. The following steps can be taken:
- Start with a careful history and physical examination to identify potential causes of jaundice 2
- Directed imaging of the biliary tree and liver can help identify any obstructions or lesions 2
- Measure bilirubin levels and its metabolites in serum, urine, and feces using various analytical methods, such as diazo transfer reaction, high-performance liquid chromatography (HPLC), and direct spectrophotometry 3
- Assess alterations in bilirubin concentrations in relation to patient anamnesis, the degree of the alteration, and the pattern of concurrent biochemical alterations 3
Potential Causes of Elevated Bilirubin
Several conditions can cause elevated bilirubin levels, including:
- Hemolytic anemia, which can be caused by various hereditary or acquired diseases 4, 5, 6
- Liver disease, which can impair the uptake, conjugation, and clearance of bilirubin 2, 3
- Bile duct obstruction, which can cause elevated direct bilirubin levels 3
- Excess bilirubin production, such as in pathologic hemolysis 3
Diagnostic Evaluation
The diagnostic evaluation of elevated bilirubin levels should include:
- Laboratory tests, such as complete blood count, reticulocyte count, lactate dehydrogenase, and haptoglobin levels 4, 5, 6
- Imaging studies, such as ultrasound or computed tomography, to evaluate the biliary tree and liver 2
- Directed testing, such as the Coombs test or hemoglobin electrophoresis, to identify specific causes of hemolytic anemia 4, 6