What is the cause of transaminase elevation and acute myopathy (transaminase elevation refers to elevated levels of Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT))?

From the Guidelines

Transaminase elevation and acute myopathy are most likely caused by statin-induced muscle injury, and the immediate recommendation is to discontinue the suspected offending medication, most commonly statins like atorvastatin, rosuvastatin, or simvastatin, as supported by the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol 1. The cause of transaminase elevation and acute myopathy can be attributed to various factors, but statin-induced muscle injury is a well-established cause. According to the 2018 guideline, statins can cause muscle symptoms, including myalgia, myopathy, and rhabdomyolysis, with an incidence of approximately 5% in clinical trials 1.

Key Considerations

• The 2018 guideline recommends measuring creatine kinase (CK) levels in patients with severe statin-associated muscle symptoms (SAMS) and in the presence of objective muscle weakness 1.
• An asymptomatic increase in transaminases (>3 times upper limit of normal) is an infrequent statin-associated side effect that often resolves with dose reduction or rechallenge with alternative statins 1.
• Severe statin-associated hepatotoxicity is rare, and the incidence is not impacted by routine monitoring of transaminases 1.

Management Strategy

• Discontinue the suspected offending medication, most commonly statins, and monitor CK levels, liver enzymes (ALT, AST), and assess renal function with creatinine and BUN tests.
• For mild cases (CK < 5x upper limit of normal), monitoring may be sufficient after drug discontinuation.
• For severe cases (CK > 10x upper limit of normal or symptoms of rhabdomyolysis), intravenous hydration with normal saline at 150-200 mL/hour should be initiated to prevent kidney injury, with hospital admission for monitoring.
• After resolution, if cholesterol management is still needed, consider alternative medications like ezetimibe 10 mg daily or PCSK9 inhibitors, or a different statin at a lower dose with careful monitoring, as recommended by the 2018 guideline 1. Some studies suggest that statin use may be associated with a rare but increased risk of polyneuropathy, as noted in the acc/aha/nhlbi clinical advisory on the use and safety of statins 1. However, this association is not consistently found in large blinded randomized controlled trials. Complete recovery from statin-induced muscle injury typically occurs within 2-6 weeks after medication discontinuation.

From the Research

Causes of Transaminase Elevation and Acute Myopathy

• Transaminase elevation, referring to elevated levels of Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT), can be caused by various factors, including liver damage and muscle injury 2, 3.
• In cases of idiopathic inflammatory myopathies, elevated transaminases, including AST and ALT, have been observed concomitantly with the activity of myositis, and approximately half of these cases could not be associated with coexisting liver disease 2.
• A study found that serum transaminases were frequently elevated at the time of diagnosis of idiopathic inflammatory myopathy and normalized with creatine kinase, suggesting a strong correlation between CK and serum transaminases 3.
• Acute myopathy of intensive care, which occurs in critically ill patients treated with intravenous corticosteroids and neuromuscular junction-blocking agents, can also cause elevated transaminases 4.
• Other causes of transaminase elevation include choledocholithiasis, which can present with very high transaminase levels, and ischemic hepatitis, acute viral hepatitis, and drug-induced liver injury 5, 6.

Relationship Between Transaminase Elevation and Muscle Injury

• Elevated transaminases, including AST and ALT, can be indicators of muscle damage, and a strong correlation has been found between CK and serum transaminases in patients with idiopathic inflammatory myopathy 3.
• Muscle histopathology has revealed myopathy with loss of thick filaments in patients with acute myopathy of intensive care, which can cause elevated transaminases 4.
• The elevation of transaminases in cases of muscle injury can be attributed to the release of these enzymes from damaged muscle cells 2, 3.

Clinical Implications

• The elevation of transaminases in patients with idiopathic inflammatory myopathy or acute myopathy of intensive care should be recognized as a potential indicator of muscle damage, rather than solely as a sign of liver disease 2, 3, 4.
• Appropriate recognition of these laboratory changes can help reduce unnecessary hepatic evaluation, delayed diagnosis, and misdiagnosis of primary liver disease 3.