Can rhabdomyolysis cause elevated Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) or abnormal liver function tests?

Can Rhabdomyolysis Cause Elevated AST and ALT?

Yes, rhabdomyolysis commonly causes elevated AST and ALT, with AST elevation being nearly universal (93% of cases) and significantly more pronounced than ALT elevation (75% of cases), because skeletal muscle is a major source of these aminotransferases, particularly AST. 1, 2

Understanding the Mechanism

Skeletal muscle contains both AST and ALT enzymes, which are released into the bloodstream during muscle injury. When rhabdomyolysis occurs, the massive breakdown of muscle tissue releases these aminotransferases along with creatine kinase (CK), myoglobin, and other intracellular contents. 3

• AST is highly concentrated in skeletal muscle and is released in parallel with CK during rhabdomyolysis, making it the predominant aminotransferase elevation in muscle injury. 2
• ALT is present in skeletal muscle but at lower concentrations than in liver tissue, which explains why ALT elevations are less pronounced than AST elevations in rhabdomyolysis. 4

Pattern of Enzyme Elevation

The characteristic pattern in rhabdomyolysis is AST-dominant elevation with an AST:ALT ratio typically >1, which helps distinguish muscle injury from primary liver disease. 5

• AST concentrations decrease in parallel with CK levels during the first 6 days of hospitalization, confirming that skeletal muscle is the primary source of AST elevation rather than liver injury. 2
• In severe rhabdomyolysis (CK ≥10,000 U/L), median AST peaks around 398 U/L and ALT around 106 U/L, demonstrating the AST-predominant pattern. 6
• There is a strong positive correlation between CK and AST (r=0.89) and a moderate correlation between CK and ALT (r=0.73), further supporting muscle as the source. 6

Distinguishing Muscle from Liver Injury

The critical diagnostic step is measuring CK levels, which will be markedly elevated in rhabdomyolysis (typically >1,000 U/L and often >10,000 U/L in severe cases). 1, 7

• If CK is markedly elevated alongside aminotransferases, the source is skeletal muscle rather than liver, avoiding unnecessary hepatic workup. 1, 7
• In contrast, primary liver diseases typically show different patterns: alcoholic liver disease has AST:ALT ratio >2:1, while NAFLD has AST:ALT ratio <1. 1, 7
• Aminotransferases lack tissue specificity, meaning elevated AST and ALT alone cannot distinguish between liver and muscle injury without additional testing. 3

Common Clinical Pitfall

The major pitfall is misinterpreting elevated aminotransferases as primary liver injury and initiating extensive hepatic investigations including liver biopsy, when the source is actually skeletal muscle. 3

• Always check CK levels when encountering elevated aminotransferases in patients with potential muscle injury (trauma, prolonged immobilization, intense exercise, drug-induced myopathy, seizures). 1, 7
• AST can be elevated from cardiac muscle, skeletal muscle, kidneys, brain, and red blood cells, not just liver, making it a non-specific marker. 4
• Even in patients with concurrent liver disease, the degree of aminotransferase elevation in rhabdomyolysis is not significantly different, so rhabdomyolysis should be considered first when muscle injury is suspected. 5

Actual Liver Injury in Severe Rhabdomyolysis

In severe rhabdomyolysis, true hepatic injury can occur through oxidative stress and other pathophysiological mechanisms, evidenced by elevated bilirubin and alkaline phosphatase. 3, 6

• When CK levels are ≥10,000 U/L, bilirubin and alkaline phosphatase are significantly elevated, suggesting actual hepatocellular damage beyond simple enzyme release from muscle. 6
• The positive correlation between CK and bilirubin (r=0.37) and alkaline phosphatase (r=0.41) indicates hepatic damage occurs when rhabdomyolysis is severe. 6