Can elevated creatine kinase (CK) levels cause elevated liver function tests (LFTs) in patients with or without a history of liver disease or muscle disorders?

Can Elevated CK Cause Elevated LFTs?

Yes, elevated creatine kinase (CK) from muscle injury can cause elevated liver function tests (specifically AST and ALT) because these enzymes are released from damaged muscle tissue, not just from the liver. This is a well-recognized phenomenon that can lead to misdiagnosis of liver disease when the true source is muscle injury.

Mechanism of CK-Related LFT Elevation

• AST and ALT are present in both liver and muscle tissue, and when muscle injury occurs, these aminotransferases leak into the bloodstream alongside CK 1.

• Testing for CK, aldolase, or other muscle-related enzymes can confirm the non-hepatic origin of elevated AST and ALT 1.

• Intensive exercise (such as weight lifting), statin-related muscle injury, or any cause of rhabdomyolysis can lead to acute elevation in AST and ALT that mimics acute liver injury 1.

Clinical Context and Differential Diagnosis

When evaluating elevated LFTs, always consider muscle injury as a potential source, especially in these scenarios:

• Patients starting intensive exercise programs as part of lifestyle modifications 1
• Patients on statin therapy who may develop muscle injury 1, 2
• Any condition causing rhabdomyolysis, where CK levels can range from 10,000 to 200,000 U/L or even higher (up to 1 million U/L in severe cases) 3
• Patients with muscle disorders such as Pompe disease, where approximately 95% of late-onset patients have elevated CK, and serum enzymes such as AST, ALT, or LDH may be elevated reflecting enzymes released from muscle 1

Key Distinguishing Features

ALT is more liver-specific than AST, making the pattern of elevation important:

• If AST is elevated disproportionately higher than ALT, consider non-hepatic causes including muscle injury 1
• Normal ALT levels are 29-33 IU/L in men and 19-25 IU/L in women, and elevations specific to the liver should show ALT predominance 1
• AST elevations can occur from disorders involving heart, skeletal muscle, kidneys, brain, and red blood cells 1

Practical Diagnostic Approach

When faced with elevated LFTs of unclear etiology, follow this algorithm:

1. Check CK levels immediately to rule out muscle injury as the source 1
2. Assess for recent physical activity, new exercise programs, or trauma 1
3. Review medication list for statins or other drugs that can cause muscle injury 1, 2
4. Evaluate the AST/ALT ratio: AST predominance suggests muscle source 1
5. Consider additional muscle markers such as aldolase if diagnosis remains unclear 1

Common Clinical Pitfalls

Do not assume elevated AST/ALT always indicates primary liver disease without first excluding muscle injury 1. This is particularly important in:

• NASH clinical trials where patients may start intensive exercise programs 1
• Patients on concomitant statin therapy for dyslipidemia 1
• Any patient presenting with muscle symptoms (pain, weakness, dark urine) 2, 3

In patients with known liver disease, muscle injury can still be the cause of acute LFT changes 1. The presence of underlying liver disease does not exclude muscle injury as a contributor to enzyme elevations.

Special Populations

In patients with cirrhosis, the relationship between muscle and liver markers becomes more complex, as decreased muscle mass affects creatinine production and CK clearance may be impaired 4, 5. The liver and blood cells are primarily responsible for CK clearance in blood circulation 4.

In patients with multiple etiologic factors (such as cocaine use, alcohol abuse, infections), rhabdomyolysis can be massive with CK levels reaching exceptionally high values, and this will significantly elevate AST and ALT 3.