Can elevated liver enzymes, specifically alanine transaminase (ALT) and aspartate transaminase (AST), be caused by Prednisone in a patient with ulcerative colitis (UC) on Entyvio (Natalizumab)?

Elevated Liver Enzymes Due to Prednisone in a Patient with Ulcerative Colitis on Entyvio

Yes, the drastic elevation in ALT and AST after starting prednisone is likely due to the prednisone itself, as corticosteroids can rarely cause drug-induced liver injury. 1

Mechanism and Presentation

• Prednisone-induced hepatotoxicity typically presents as a mixed hepatocellular and cholestatic liver injury pattern
• While rare, methylprednisolone (related to prednisone) has been documented to cause significant elevations in liver enzymes, with reported cases showing ALT >2000 U/L 1
• The onset of steroid-induced liver injury typically occurs within days to weeks after initiation

Assessment of Liver Enzyme Elevations

Severity Classification

• Grade 1: AST/ALT > ULN to 3× ULN
• Grade 2: AST/ALT > 3× to 5× ULN
• Grade 3: AST/ALT > 5× to 20× ULN
• Grade 4: AST/ALT > 20× ULN 2

Initial Evaluation

1. Confirm pattern of liver enzyme elevation (hepatocellular vs. cholestatic)
2. Rule out other causes:
   • Viral hepatitis (hepatitis A/B/C/E)
   • Autoimmune hepatitis
   • Biliary obstruction
   • Alcohol consumption
   • Thromboembolic events
   • Metastatic disease 2, 3

Management Algorithm

For Grade 2 Elevation (AST/ALT >3-5× ULN):

1. Hold prednisone temporarily
2. Monitor liver enzymes every 2-3 days
3. Consider alternative treatments for ulcerative colitis flare 2

For Grade 3 Elevation (AST/ALT >5-20× ULN):

1. Discontinue prednisone
2. Obtain urgent gastroenterology/hepatology consultation
3. Monitor liver enzymes every 1-2 days
4. Consider liver biopsy if no improvement 2

For Grade 4 Elevation (AST/ALT >20× ULN):

1. Permanently discontinue prednisone
2. Hospitalize the patient
3. Monitor liver enzymes daily
4. Consider transfer to a center with expertise in liver failure management 2

Special Considerations for UC Patients on Entyvio

• Entyvio (vedolizumab) is not typically associated with significant hepatotoxicity
• For UC flare management without prednisone, consider:
  • Budesonide (has lower systemic effects)
  • Biologics like infliximab (if not contraindicated)
  • Vedolizumab dose optimization 2

Important Caveats and Pitfalls

• Prednisone is paradoxical in liver disease - it's typically used to treat certain types of hepatitis but can rarely cause hepatotoxicity itself
• Do not restart prednisone once hepatotoxicity is confirmed, as rechallenge can lead to more severe injury 1
• Patients with pre-existing liver disease may have altered prednisone metabolism, leading to higher prednisolone concentrations 4
• High-dose prednisone (>40mg/day) may be more likely to cause hepatotoxicity than lower doses 5
• Monitor for signs of liver decompensation (jaundice, ascites, encephalopathy) which would indicate severe injury 6

Follow-up Recommendations

• Monitor liver enzymes every 2-3 days until improving
• Once improving, check weekly until normalized
• Consider alternative UC treatments that don't involve systemic corticosteroids
• If liver enzymes don't improve within 1-2 weeks after stopping prednisone, consider liver biopsy to rule out other causes 2

Remember that while prednisone-induced hepatotoxicity is rare, it should be considered in the differential diagnosis when liver enzymes rise after initiating steroid therapy, especially when other causes have been excluded.