What is the management plan for a patient with newly elevated Liver Function Tests (LFTs) after 2 days of normal LFTs in sepsis?

Management of Newly Elevated Liver Function Tests in Sepsis

For a patient with newly elevated liver function tests after 2 days of normal LFTs in sepsis, a comprehensive evaluation for potential causes should be performed while continuing sepsis management, as abnormal LFTs are more commonly attributable to secondary effects of sepsis rather than primary liver disease. 1

Immediate Assessment

• Evaluate for treatment-related GI and hepatic adverse effects, as many medications used in sepsis management can cause liver enzyme elevations 1
• Review all current medications, particularly those with known hepatotoxicity potential (antimicrobials, statins, acetaminophen) 1, 2
• Obtain fractionated bilirubin tests to determine if the hyperbilirubinemia is conjugated or unconjugated 3
• Monitor LFTs throughout hospitalization, especially in patients receiving potentially hepatotoxic medications 1

Potential Causes of Newly Elevated LFTs in Sepsis

• Secondary effects of sepsis including:

  • Systemic inflammatory response syndrome 1
  • Cytokine storm 1
  • Ischemic hepatitis/shock 1
  • Drug hepatotoxicity 1, 4

• Medication-related causes:

  • Patients receiving potentially hepatotoxic medications during treatment have a 3-fold increased risk of developing LFT alterations 4
  • Antimicrobial agents are common culprits in drug-induced liver injury during sepsis management 1

Management Approach

• Investigate non-COVID-19/non-sepsis causes of liver disease in all patients with abnormal LFTs 1
• Consider hepatitis serology (HBsAg, anti-HBc IgM, anti-HAV IgM) to rule out viral causes 1, 2
• Perform abdominal ultrasound to exclude biliary obstruction, verify vessel permeability, and rule out chronic liver disease 1, 3
• Adjust medication dosages based on severity of liver dysfunction, particularly for drugs with predominant hepatic metabolism 5

Monitoring Recommendations

• For mild elevations (<5× upper limit of normal), monitor liver enzymes weekly until normalization 2
• For moderate elevations (5-10× ULN), monitor liver enzymes every 2-3 days until stable or improving 2
• For severe elevations (>10× ULN), consider more aggressive monitoring and potential medication adjustments 2

Special Considerations

• In elderly patients with bacterial sepsis, development of jaundice has been associated with increased survival, contrary to what might be expected 6
• Persistent isolated elevations of direct bilirubin with otherwise normal liver tests should be closely monitored, as this may indicate early liver disease 3
• If LFT abnormalities persist or worsen despite addressing potential medication causes, consider additional imaging or specialist consultation 2

Important Caveats

• Do not automatically discontinue all medications when LFTs become elevated, as this may compromise sepsis treatment 1
• Idiosyncratic drug reactions can occur equally in patients with normal or abnormal baseline liver function 5
• LFT abnormalities at hospital admission may be associated with higher risk for severe disease outcomes (odds ratio 2.73; 95% CI, 1.19–6.3) 1
• Medication review should be ongoing throughout hospitalization as delayed hepatotoxicity can occur even after initial normal LFTs 7