Can dexamethasone cause transaminitis (elevated liver enzymes)?

Dexamethasone and Transaminitis: Clinical Evidence and Management

Dexamethasone itself does not typically cause transaminitis (elevated liver enzymes), but rather has been shown to have hepatoprotective effects against transaminitis caused by other medications. 1

Mechanism and Evidence

Dexamethasone's relationship with liver enzymes is complex:

• Dexamethasone has been demonstrated to have a hepatoprotective effect, decreasing the rate of drug-induced ALT release from hepatocytes by approximately 63% in patients receiving trabectedin, a chemotherapeutic agent known to cause transaminitis 2

• In specific drug interaction scenarios, dexamethasone may indirectly contribute to liver enzyme elevations through its effect on drug metabolism. For example, when used with lapatinib (a tyrosine kinase inhibitor), dexamethasone can increase lapatinib metabolism, potentially increasing formation of reactive metabolites that may cause hepatotoxicity 1

• Short-term dexamethasone administration in animal studies showed increased liver ALT activity (up to 3.7-fold) but this was primarily related to enhanced ALT expression rather than hepatocellular injury in early treatment phases 3

Clinical Considerations

Monitoring Recommendations

When using dexamethasone:

• Routine monitoring of liver enzymes is generally not required for dexamethasone monotherapy in standard doses
• For patients receiving dexamethasone with other potentially hepatotoxic medications:
  • Monitor serum transaminases, alkaline phosphatase (ALP) and bilirubin regularly 1
  • Increased vigilance is warranted when dexamethasone is combined with medications known to have potential hepatotoxicity 1

Management of Transaminitis

If transaminitis occurs in a patient receiving multiple medications including dexamethasone:

• For grade 1 liver enzyme elevations (AST/ALT < 3× ULN):

  • Continue therapy with monitoring every 1-2 weeks 1

• For grade 2 liver enzyme elevations (AST/ALT 3-5× ULN):

  • Consider temporarily withholding hepatotoxic medications
  • Monitor enzymes twice weekly
  • Consider corticosteroids 0.5-1 mg/kg/day if no improvement after 3-5 days 1

• For grade 3-4 liver enzyme elevations (AST/ALT >5× ULN):

  • Discontinue hepatotoxic medications
  • Initiate corticosteroids 1-2 mg/kg/day
  • Consider hepatology consultation 1

Important Caveats

• Dexamethasone may mask symptoms of liver injury by suppressing inflammatory responses

• When evaluating transaminitis in patients on multiple medications, consider:

  • Timing of enzyme elevations relative to medication initiation
  • Pattern of liver enzyme elevation (hepatocellular vs. cholestatic)
  • Presence of risk factors for liver injury
  • Concomitant medications with known hepatotoxicity

• In cases where dexamethasone is being used with tyrosine kinase inhibitors or other hepatotoxic medications, careful monitoring is essential as drug interactions may increase risk of hepatotoxicity 1

Conclusion

Dexamethasone alone rarely causes transaminitis and is more commonly used to treat or prevent drug-induced liver injury. When transaminitis occurs in patients receiving dexamethasone, other causes should be thoroughly investigated before attributing the elevation to dexamethasone itself.