From the Guidelines
The workup for elevated bilirubin begins with determining whether the hyperbilirubinemia is predominantly unconjugated (indirect) or conjugated (direct) 1. For unconjugated hyperbilirubinemia, evaluate for hemolysis with complete blood count, peripheral smear, reticulocyte count, haptoglobin, and LDH. Consider Gilbert syndrome if mild elevation occurs without other abnormalities, as it is an inherited disorder of metabolism leading to impaired conjugation via reduced activity of the enzyme glucuronyltransferase 1. For conjugated hyperbilirubinemia, assess for liver disease with liver function tests, hepatitis serologies, and imaging studies like ultrasound or CT. Additional tests include MRCP for biliary obstruction, autoimmune markers (ANA, anti-smooth muscle antibody), and iron studies. If the cause remains unclear, consider liver biopsy. The algorithm follows a stepwise approach: first classify the type of hyperbilirubinemia, then investigate specific causes based on this classification, and finally implement targeted treatment. For unconjugated hyperbilirubinemia, address underlying hemolysis or genetic disorders. For conjugated hyperbilirubinemia, treat the underlying liver disease or relieve biliary obstruction through ERCP or surgery if present. This systematic approach is essential because bilirubin elevation can indicate various conditions ranging from benign disorders to serious hepatic or hematologic diseases requiring prompt intervention 1.
Some key points to consider in the workup and management of elevated bilirubin include:
- Differentiating between unconjugated and conjugated hyperbilirubinemia is crucial for guiding further investigation and treatment 1.
- Gilbert syndrome is a common cause of mild unconjugated hyperbilirubinemia and can be diagnosed by calculating the proportion of conjugated bilirubin, which should be less than 20%-30% of the total bilirubin 1.
- Conjugated hyperbilirubinemia often requires imaging studies to assess for biliary obstruction or liver disease 1.
- Liver biopsy may be necessary if the cause of elevated bilirubin remains unclear after initial evaluation 1.
- Treatment should be targeted at the underlying cause of the hyperbilirubinemia, whether it be hemolysis, genetic disorders, liver disease, or biliary obstruction 1.
Overall, a systematic and stepwise approach to the evaluation and management of elevated bilirubin is essential for providing optimal care and improving patient outcomes 1.
From the Research
Elevated Bilirubin Workup
The workup for elevated bilirubin involves a comprehensive medical history, review of systems, and physical examination to differentiate potential causes such as alcoholic liver disease, biliary strictures, choledocholithiasis, drug-induced liver injury, hemolysis, or hepatitis 2. Initial laboratory evaluation should include:
- Bilirubin (total and fractionated)
- Complete blood cell count
- Aspartate transaminase
- Alanine transaminase
- Gamma-glutamyltransferase
- Alkaline phosphatase
- Albumin
- Prothrombin time
- International normalized ratio
Algorithm for Evaluating Jaundice
The evaluation of jaundice relies on the history and physical examination, followed by laboratory testing and imaging 3. The algorithm for evaluating jaundice includes:
- Fractionated bilirubin to determine whether the hyperbilirubinemia is conjugated or unconjugated
- Imaging with ultrasonography or computed tomography to differentiate between extrahepatic obstructive and intrahepatic parenchymal disorders
- Additional testing such as cancer screening, biliary imaging, autoimmune antibody assays, and liver biopsy may be necessary for a more extensive evaluation
Causes of Hyperbilirubinemia
Hyperbilirubinemia can be caused by:
- Increased bilirubin production due to red blood cell destruction, such as hemolytic disorders
- Disorders of impaired bilirubin conjugation, such as Gilbert syndrome
- Hepatocellular damage, such as viral and alcoholic hepatitis
- Cholestatic disorders, such as choledocholithiasis and neoplastic obstruction of the biliary tree 3, 4
Predicting Common Bile Duct Stones
Trends in total bilirubin can be used to predict the presence of common bile duct stones (CBDS) in patients with acute cholecystitis or symptomatic cholelithiasis 5. However, prediction is not improved by following levels over time, and patients presenting with elevated serum bilirubin should undergo immediate imaging or procedural intervention rather than obtaining follow-up bilirubin levels.