What medications can cause elevated Aspartate Aminotransferase (AST) levels?

Medications That Cause Elevated AST Levels

Statins are the most common medications that cause elevated AST levels, with fluvastatin showing the highest risk (6.9 times), followed by atorvastatin (3.1 times) and simvastatin (3.0 times) compared to other medications. 1

Common Medications Associated with AST Elevation

Statins

• Statins can cause hepatic transaminase elevations, including AST, with varying degrees of risk among different agents 2, 3, 4
• Risk hierarchy based on pharmacovigilance data (from highest to lowest risk) 1:
  • Fluvastatin (highest risk, 6.9 times higher odds)
  • Atorvastatin (3.1 times higher odds)
  • Simvastatin (3.0 times higher odds)
  • Lovastatin (2.8 times higher odds)
  • Rosuvastatin (2.3 times higher odds)
  • Pravastatin (2.1 times higher odds, lowest risk among statins)
• High-intensity statin therapy increases the risk of elevated hepatic transaminases >2-3 times ULN more than moderate-dose therapy (<1.5% over 5 years) 2
• Older patients (≥65 years) show stronger signals for statin-induced liver injury, particularly with atorvastatin, simvastatin, pravastatin, and fluvastatin 1

Other Common Medications

• Niacin (immediate-release, approximately 2g dose) can cause elevated levels of serum glutamic oxaloacetic transaminase (AST) 2
• Tocilizumab causes ALT elevation in >20% of patients; ALT increase to >5 times ULN in <1% of patients 2
• Lopinavir-ritonavir can cause ALT increases to >5 times ULN in 5% of patients 2
• Interferon alfa can cause ALT increases to >2 times ULN in >25% of patients with chronic viral hepatitis 2
• Interferon beta may cause ALT increases to >3 times ULN in 10% of patients 2

Risk Factors for Medication-Induced AST Elevation

• Age ≥65 years (particularly with statins) 1, 5
• Pre-existing liver disease or chronic liver conditions 2, 5
• Alcohol consumption 3, 4
• Concomitant use of multiple hepatotoxic medications 2
• Intensive exercise (e.g., weight lifting) can lead to acute elevation in AST due to muscle injury, which can be mistaken for drug-induced liver injury 2

Clinical Approach to AST Elevation in Patients on Medications

Assessment

• Determine severity of AST elevation 2:
  • Mild: <5 times the upper reference limit
  • Moderate: 5-10 times the upper reference limit
  • Severe: >10 times the upper reference limit
• Consider non-hepatic causes of AST elevation (muscle injury, hemolysis, thyroid disease) 2, 6
• AST:ALT ratio >2 suggests alcohol-related liver disease, while ratio <1 suggests metabolic disease-related fatty liver 2

Management

• For statin-induced AST elevation 3, 4:
  • If persistent increases to more than 3× ULN in serum transaminases occur, consider discontinuation
  • Most elevations appear soon after initiation, are transient, and resolve with continued therapy or brief interruption
  • Consider liver enzyme testing before statin initiation and when clinically indicated thereafter
• For niacin-induced AST elevation 2:
  • Baseline hepatic transaminases should be obtained before initiation
  • Monitor during up-titration to maintenance dose and every 6 months thereafter
  • Niacin should not be used if hepatic transaminase elevations are higher than 2-3 times ULN

Important Caveats and Pitfalls

• AST elevation may be non-hepatic in origin - always check creatine kinase (CK) levels to rule out muscle injury, especially in patients on statins who exercise 2
• Isolated AST elevation without ALT elevation may indicate macro-AST, a benign condition that can be confirmed with polyethylene glycol precipitation tests 6
• Extreme elevations of AST (>3000 U/L) are rarely medication-induced and more commonly due to ischemic/hypoxic hepatitis or viral hepatitis 7
• In patients with NASH (non-alcoholic steatohepatitis), ALT elevation of ≥5× ULN is rare and usually should not be attributed to NASH, especially if this represents a significant change from baseline 2
• Patients with long-standing T2DM and other features of metabolic syndrome have higher risk of liver conditions that may cause AST elevation independent of medications 2

Remember that while medications can cause AST elevation, it's essential to rule out other causes such as viral hepatitis, autoimmune hepatitis, gallstone disease, or other liver conditions before attributing the elevation solely to medication effects 2.