Can prednisone (corticosteroid) increase liver enzymes, specifically alanine transaminase (ALT) and aspartate transaminase (AST)?

Can Prednisone Increase Liver Enzymes?

Yes, prednisone can cause elevations in liver enzymes (ALT and AST), though this is relatively uncommon. While corticosteroids like prednisone are generally used to treat inflammatory liver conditions, they can paradoxically cause hepatotoxicity in some cases.

Mechanism and Incidence

Prednisone-related liver enzyme elevations typically manifest as:

• Mild to moderate increases in ALT and AST
• Mixed hepatocellular and cholestatic pattern of injury
• Usually occurring within the first few weeks of treatment

The exact mechanism is not fully understood but may involve:

1. Direct hepatotoxic effects
2. Idiosyncratic drug reactions
3. Altered metabolism of prednisone in patients with impaired liver function 1

Evidence from Clinical Guidelines

Current guidelines acknowledge the potential for corticosteroid-induced liver injury:

• The British Society of Gastroenterology (BSG) notes that about 25% of patients on immunosuppressive regimens (including corticosteroids) develop side effects 2
• The European Association for the Study of the Liver (EASL) guidelines specifically mention that methylprednisolone (related to prednisone) has been associated with drug-induced liver autoimmune-like hepatitis 2

Monitoring Recommendations

For patients on prednisone therapy:

• Baseline liver function tests before starting therapy
• Regular monitoring of liver enzymes (ALT, AST) during treatment:
  • Weekly for the first 4 weeks
  • Monthly thereafter if stable
  • More frequently if abnormalities develop

Risk Factors for Prednisone-Induced Liver Injury

Patients at higher risk include those with:

• Pre-existing liver disease
• Higher doses of prednisone (>40 mg/day) 3
• Concurrent use of other potentially hepatotoxic medications
• Impaired liver function, which can decrease prednisone metabolism 1

Management of Prednisone-Related Liver Enzyme Elevations

If liver enzyme elevations occur:

1. For mild elevations (1-3× ULN):

   • Continue monitoring more frequently
   • Consider dose reduction if clinically appropriate

2. For moderate elevations (3-5× ULN):

   • Consider dose reduction
   • Evaluate for other causes of liver injury
   • More frequent monitoring

3. For severe elevations (>5× ULN):

   • Consider discontinuation of prednisone if clinically feasible
   • Consult with hepatology
   • Investigate for alternative causes

Clinical Perspective

It's important to note that while prednisone can cause liver enzyme elevations, it is also a primary treatment for many immune-mediated liver conditions. The American Association for the Study of Liver Diseases (AASLD) guidelines indicate that prednisone is the cornerstone of therapy for autoimmune hepatitis despite its potential hepatotoxic effects 2.

Case Reports and Research Evidence

There are documented cases of methylprednisolone (related to prednisone) causing hepatotoxicity:

• A case report described a patient who developed mixed hepatocellular and cholestatic liver injury after taking methylprednisolone, with resolution after discontinuation 4

Conclusion

While prednisone is generally considered safe for the liver and is used to treat liver inflammation, clinicians should be aware of its potential to cause liver enzyme elevations. Regular monitoring of liver function tests is recommended, especially during the initial weeks of therapy and in patients with risk factors for hepatotoxicity.