What are the treatment options for elevated bilirubin levels?

Treatment Options for Elevated Bilirubin Levels

The treatment approach for elevated bilirubin depends primarily on whether the hyperbilirubinemia is predominantly conjugated or unconjugated, the patient's age, and the underlying cause. 1

Initial Diagnostic Evaluation

• Determine whether hyperbilirubinemia is predominantly conjugated or unconjugated by obtaining fractionated bilirubin levels 1
• Order complete liver function tests including ALT, AST, ALP, GGT, and albumin to assess for liver injury and synthetic function 1
• Measure prothrombin time (PT) and INR to evaluate liver synthetic capacity 1
• Obtain complete blood count with peripheral smear to assess for hemolysis if unconjugated hyperbilirubinemia is suspected 1

Treatment Based on Bilirubin Type

For Unconjugated Hyperbilirubinemia:

• For Gilbert's syndrome (most common cause of isolated elevated bilirubin), no specific treatment is required as it's a benign condition 2, 3
• For hemolytic causes, identify and treat the underlying condition with appropriate therapies 1
• For neonatal unconjugated hyperbilirubinemia:
  • Phototherapy is the mainstay of treatment when total serum bilirubin (TSB) reaches treatment thresholds 2, 4
  • Exchange transfusion is recommended for severe cases with TSB ≥25 mg/dL or signs of acute bilirubin encephalopathy 2, 1
  • Intravenous immunoglobulin (0.5-1 g/kg over 2 hours) is recommended for isoimmune hemolytic disease if TSB is rising despite intensive phototherapy 1

For Conjugated Hyperbilirubinemia:

• Treatment targets the underlying cause:
  • For biliary obstruction, consider preoperative biliary drainage if total bilirubin >12.8 mg/dL, especially if major hepatic resection is planned 1
  • For hepatocellular causes, treat the underlying liver disease 5
  • For neonates and infants with conjugated bilirubin >25 μmol/L, urgent referral to a pediatrician for assessment of possible liver disease is essential 2, 1

Special Considerations for Neonates

• Intensive phototherapy should be used when TSB exceeds treatment thresholds based on age and risk factors 2
  • "Intensive phototherapy" requires irradiance in the blue-green spectrum (430-490 nm) of at least 30 mW/cm² per nm delivered to as much of the infant's surface area as possible 2
• Exchange transfusion should only be performed by trained personnel in a neonatal intensive care unit with full monitoring and resuscitation capabilities 1
• Treatment thresholds are lower for younger infants and those with risk factors for bilirubin neurotoxicity 1

Treatment for Medication-Induced Hyperbilirubinemia

• For antiviral medication-induced hyperbilirubinemia:
  • Mild indirect hyperbilirubinemia associated with impaired conjugation is usually well tolerated and may not require intervention 6
  • Modification in antiviral drug choice or dose may be required in cases of liver injury or brisk hemolysis leading to significant anemia 6

Pitfalls to Avoid

• Do not subtract direct (conjugated) bilirubin from total bilirubin when making treatment decisions in neonates 1
• Avoid overinterpreting albumin concentrations as a marker of liver disease severity 2
• Do not delay appropriate imaging in patients with conjugated hyperbilirubinemia, as early identification of biliary obstruction is critical for timely intervention 1
• Be aware that standard laboratory tests for hemolysis have poor specificity and sensitivity in neonates 1

Emerging Therapies

• Tin-mesoporphyrin, a drug that inhibits heme oxygenase production, could be considered for preventing the need for exchange transfusion in infants not responding to phototherapy, though it is not yet FDA approved 1