From the Guidelines
The workup of elevated total bilirubin should begin with fractionating the bilirubin to determine the percentage derived from direct bilirubin, as recommended by the consensus guidelines 1. This initial step is crucial in differentiating between unconjugated and conjugated hyperbilirubinemia, which guides further investigation and management. The most recent and highest quality study, published in 2020, emphasizes the importance of this initial fractionation 1.
Key Steps in the Workup
- Order a fractionated bilirubin test to distinguish between unconjugated and conjugated hyperbilirubinemia.
- For unconjugated hyperbilirubinemia, evaluate for hemolysis with complete blood count, peripheral smear, reticulocyte count, haptoglobin, and LDH, and consider Gilbert syndrome if mild elevation occurs without other abnormalities.
- For conjugated hyperbilirubinemia, assess liver function with ALT, AST, alkaline phosphatase, GGT, albumin, and PT/INR, and consider additional tests such as hepatitis serologies, autoimmune markers, and imaging studies to identify biliary obstruction or structural abnormalities.
Imaging and Further Evaluation
- If obstruction is suspected, MRCP or ERCP may be necessary for further evaluation and potential intervention, as suggested by the American College of Radiology 1.
- In cases without clear etiology after initial testing, consider liver biopsy, taking into account the patient's clinical status and the potential risks and benefits of the procedure.
Prioritizing Patient Outcomes
The approach to elevated total bilirubin should prioritize the identification of the underlying cause, whether it stems from increased bilirubin production, impaired hepatic uptake, decreased conjugation, or obstructed biliary excretion, to guide appropriate management and improve patient outcomes, as emphasized by guidelines on the management of abnormal liver blood tests 1.
From the Research
Evaluating Elevated Total Bilirubin
To work up elevated total bilirubin, the following steps can be taken:
- Start with a careful history and physical examination to identify any underlying disease states 2
- Directed imaging of the biliary tree and liver can help identify any liver lesions or bile duct defects 2, 3
- Measure bilirubin levels using various analytical methods, such as diazo transfer reaction, high-performance liquid chromatography (HPLC), or 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
Common Causes of Elevated Bilirubin
Elevated bilirubin levels can be caused by:
- Excess bilirubin production (e.g., pathologic hemolysis) 3, 4, 5
- Impaired liver uptake or conjugation 3
- Bile clearance defects or inability of the bile to reach the small bowel through bile ducts 3
- Liver lesions or diseases, such as sickle cell disease 4
Laboratory Evaluation
Laboratory tests that can be used to evaluate elevated bilirubin include:
- Reticulocyte count to assess bone marrow response 4, 5
- Lactate dehydrogenase (LDH) to assess intravascular hemolysis 4, 5
- Aspartate aminotransferase (AST) to assess liver damage 4
- Direct antiglobulin test to diagnose autoimmune hemolytic anemia 5
- Blood smear examination to diagnose congenital membrane defects or thrombotic microangiopathies 5