From the Guidelines
Elevated bilirubin levels should be interpreted by distinguishing between unconjugated (indirect) and conjugated (direct) hyperbilirubinemia to determine the underlying cause, which can be broadly categorized as pre-hepatic, hepatic, or post-hepatic 1. When interpreting elevated bilirubin, it is essential to consider the clinical presentation, laboratory findings, and imaging studies to guide diagnosis and management.
- Unconjugated hyperbilirubinemia suggests hemolysis, genetic disorders like Gilbert's syndrome, or ineffective erythropoiesis.
- Conjugated hyperbilirubinemia indicates liver disease or biliary obstruction. A complete workup should include:
- Liver function tests
- Complete blood count
- Imaging studies such as ultrasound or CT scan Mild elevations (less than 3 mg/dL) may be monitored, while levels above 3 mg/dL typically warrant more urgent evaluation 1. Treatment depends on the underlying cause—hemolysis may require addressing the underlying condition, biliary obstruction might need endoscopic or surgical intervention, while hepatocellular causes may require specific treatments for the liver disease. Patients with jaundice, dark urine, clay-colored stools, or signs of liver failure need immediate medical attention, as indicated by the most recent guidelines on the management of abnormal liver blood tests 1. The pattern of bilirubin elevation, along with other laboratory findings, helps guide diagnosis and management, as bilirubin is produced from the breakdown of hemoglobin and normally processed by the liver for excretion. In clinical practice, differentiating between the various potential etiologies of jaundice requires a detailed history, targeted physical examination, and pertinent laboratory studies, the results of which allow the physician to categorize the type of jaundice 1. The most common causes of jaundice vary by geography, type of hospital, and demographics, but in the United States, the most common causes include hepatitis, alcoholic liver disease, blockage of the common bile duct by a gallstone or tumor, and toxic reaction to a drug or medicinal herb 1. It is crucial to consider these factors when interpreting elevated bilirubin levels to provide appropriate management and improve patient outcomes.
From the Research
Interpretation of Hyperbilirubinemia
Hyperbilirubinemia, or elevated bilirubin, can be interpreted as an indication of derangements in bilirubin metabolism, which may be caused by various underlying diseases of the liver or biliary tract 2, 3. The evaluation of hyperbilirubinemia relies on a comprehensive medical history, review of systems, and physical examination, as well as laboratory tests and imaging studies.
Causes of Hyperbilirubinemia
The causes of hyperbilirubinemia can be categorized into two main types:
- Unconjugated hyperbilirubinemia, which occurs with increased bilirubin production caused by red blood cell destruction, such as hemolytic disorders, and disorders of impaired bilirubin conjugation, such as Gilbert syndrome 3, 4.
- Conjugated hyperbilirubinemia, which occurs in disorders of hepatocellular damage, such as viral and alcoholic hepatitis, and cholestatic disorders, such as choledocholithiasis and neoplastic obstruction of the biliary tree 3, 4.
Laboratory Evaluation
The laboratory evaluation of hyperbilirubinemia should include assays for bilirubin (total and fractionated), a complete blood cell count, liver function tests, and coagulation tests 2, 3, 4. Measuring fractionated bilirubin allows for determination of whether the hyperbilirubinemia is conjugated or unconjugated.
Imaging Studies
Imaging studies, such as ultrasonography, computed tomography, and magnetic resonance cholangiopancreatography, can help differentiate between extrahepatic obstructive and intrahepatic parenchymal disorders 2, 3. Ultrasonography is the least invasive and least expensive imaging method.
Clinical Significance
Elevated plasma bilirubin levels are a frequent clinical finding, and can be secondary to alterations in any stage of its metabolism 5. The evaluation of bilirubin concentrations should be assessed in relation to patient anamnesis, the degree of the alteration, and the pattern of concurrent biochemical alterations. In some cases, high levels of unconjugated bilirubin can reflect a persistent defect in bilirubin conjugation in relationship with liver centrilobular injury 6.