What is the correlation between Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) levels and medication use?

From the Guidelines

Elevated AST and ALT levels are a significant concern when it comes to medications, and regular monitoring is crucial to prevent liver damage, as recommended by the most recent study 1. When considering the correlation between AST, ALT, and medications, it's essential to prioritize the patient's morbidity, mortality, and quality of life. The most recent study 1 provides guidelines for the detection, assessment, and management of suspected immune-mediated liver injury caused by immune checkpoint inhibitors.

Key Points to Consider:

• In patients with normal or near-normal baseline serum ALT, an increase of ALT to ≥3x ULN should prompt an evaluation for possible causes, including possible immune-mediated liver injury versus tumor progression 1.
• In patients with elevated baseline serum ALT, an increase of ALT to ≥2x baseline should prompt an evaluation for possible causes, including possible immune-mediated liver injury versus tumor progression 1.
• Regular liver function monitoring is recommended when starting potentially hepatotoxic medications, particularly during the first 6 months of therapy 1.

Medications that Can Affect Liver Enzymes:

• Statins (atorvastatin, simvastatin)
• Acetaminophen (especially at doses >4g/day)
• NSAIDs (diclofenac, naproxen)
• Antibiotics (amoxicillin-clavulanate, isoniazid, rifampin)
• Antiepileptics (valproic acid, phenytoin)
• Certain antidepressants (duloxetine)

Recommendations:

• For mild elevations (less than 3 times upper limit of normal), monitoring may be sufficient while continuing necessary medications.
• For moderate elevations (3-5 times normal), dose reduction or temporary discontinuation might be needed.
• Severe elevations (>5 times normal) typically require immediate discontinuation of suspected medications. The pattern of elevation can provide clues—hepatocellular injury typically shows greater ALT elevation, while cholestatic patterns show more alkaline phosphatase elevation 1. Recovery after medication discontinuation usually occurs within 2-8 weeks, though some drugs like amiodarone may cause prolonged elevations.

Monitoring and Management:

• Regular liver function monitoring is recommended when starting potentially hepatotoxic medications, particularly during the first 6 months of therapy 1.
• Failure to respond to discontinuation of medications and initiation of corticosteroid therapy within 4–6 weeks should warrant a repeat evaluation for other possible causes of liver injury and consideration of a liver biopsy 1.

From the FDA Drug Label

Elevations in Liver Enzyme Tests Persistent elevations in serum transaminases, defined as more than 3 times the ULN and occurring on 2 or more occasions, occurred in 0. 7% of patients who received atorvastatin calcium in clinical trials. The incidence of these abnormalities was 0.2%, 0.2%, 0.6%, and 2. 3% for 10,20,40, and 80 mg, respectively. One patient in clinical trials developed jaundice. Increases in liver enzyme tests in other patients were not associated with jaundice or other clinical signs or symptoms. Upon dose reduction, drug interruption, or discontinuation, transaminase levels returned to or near pretreatment levels without sequelae Eighteen of 30 patients with persistent liver enzyme elevations continued treatment with a reduced dose of atorvastatin calcium.

The medication atorvastatin has been associated with elevations in liver enzyme tests, including AST and ALT, in some patients. The incidence of these abnormalities varied by dose, with higher doses associated with a greater risk of elevation. In some cases, patients with persistent liver enzyme elevations were able to continue treatment with a reduced dose of atorvastatin calcium. 2

• Key points:
  • Elevations in liver enzyme tests occurred in 0.7% of patients receiving atorvastatin calcium.
  • The incidence of these abnormalities varied by dose.
  • Patients with persistent liver enzyme elevations may be able to continue treatment with a reduced dose.

From the Research

AST and ALT Correlation with Medications

• The correlation between AST and ALT levels and medications, particularly statins, has been studied in various research papers 3, 4, 5.
• Statins have been shown to cause mild elevations of ALT and AST levels in some patients, but these elevations are generally not associated with significant liver toxicity 3, 4.
• The incidence of mild ALT and AST elevation in patients taking statins is around 2-3%, and is more common in older adults and those with chronic liver disease 4.
• Other medications, such as those used to lower LDL, may also affect AST and ALT levels, but the evidence is limited 3.
• The evaluation of abnormal liver chemistries, including AST and ALT levels, should include a history of prescribed and over-the-counter medicines, as well as testing for viral hepatitis, nonalcoholic fatty liver disease, and other liver conditions 6.
• The safety and effectiveness of statins as a class, and of specific statins, have been evaluated in several studies, with some statins showing a better safety profile than others 5.
• The benefits and harms of statins, including their effects on AST and ALT levels, should be carefully considered in the management of cardiovascular disease 5.