Are elevated transaminases (liver enzymes) common in patients with rhabdomyolysis?

Elevated Transaminases in Rhabdomyolysis

Yes, elevated transaminases (AST and ALT) are very common in rhabdomyolysis, occurring frequently in severe cases due to release of these enzymes from injured skeletal muscle, not necessarily indicating liver injury. 1, 2

Mechanism and Frequency of Transaminase Elevation

• Skeletal muscle contains both AST and ALT, which are released into the circulation during muscle breakdown alongside creatine kinase (CK) and myoglobin. 1
• In severe rhabdomyolysis (CK ≥10,000 U/L), transaminase elevations are significantly more pronounced, with median AST peaks of 398 U/L (range 270-944) and median ALT peaks of 106 U/L (range 77-235) compared to mild rhabdomyolysis cases. 2
• A strong positive linear correlation exists between CK levels and both AST (r = 0.89, p<0.0001) and ALT (r = 0.73, p<0.0001), demonstrating that transaminase elevation parallels the severity of muscle injury. 2

Distinguishing Muscle-Origin vs. Liver-Origin Transaminases

• AST is significantly less liver-specific than ALT because it is present in cardiac muscle, skeletal muscle, kidneys, brain, and red blood cells, making it particularly elevated in rhabdomyolysis. 3
• The AST:ALT ratio is typically >1 in rhabdomyolysis (often >2), with AST disproportionately elevated compared to ALT, which differs from most primary liver diseases where ALT predominates (AST:ALT <1). 3, 4, 2
• Creatine kinase should always be measured when evaluating elevated transaminases to exclude muscle injury as the source, particularly if the patient has engaged in intensive exercise, experienced trauma, or has other risk factors for rhabdomyolysis. 3

Clinical Presentation and Associated Findings

• Rhabdomyolysis ranges from asymptomatic laboratory abnormalities to life-threatening complications including acute kidney injury, severe electrolyte disorders, and cardiac instability. 5, 6
• The diagnosis is established by elevation of serum muscle enzymes including CK, myoglobin, lactate dehydrogenase (LDH), and transaminases. 5, 7
• In severe rhabdomyolysis, alkaline phosphatase and bilirubin may also be elevated (median ALP 84 U/L vs 52 U/L in mild cases, p=0.0063; median bilirubin 39 U/L vs 14 U/L, p=0.0031), suggesting potential hepatic involvement beyond simple enzyme release. 2

Important Clinical Pitfalls

• Do not assume transaminase elevation indicates primary liver injury in the setting of suspected or confirmed rhabdomyolysis without checking CK levels first. 1
• Avoid triggering unnecessary liver investigations (including liver biopsy) when elevated transaminases are proportional to CK elevation and the AST:ALT ratio is >1. 1
• The combination of markedly elevated CK (typically >1,000 U/L, often >10,000 U/L in severe cases) with elevated transaminases and an AST:ALT ratio >1 strongly suggests muscle origin rather than primary hepatic pathology. 6, 2

When to Suspect Actual Liver Injury

• If bilirubin and alkaline phosphatase are significantly elevated alongside transaminases in severe rhabdomyolysis, this may indicate actual hepatic damage rather than simple enzyme release from muscle. 2
• Oxidative stress from severe rhabdomyolysis may cause genuine liver injury through pathophysiological mechanisms beyond simple enzyme release. 1
• Consider abdominal ultrasound if transaminases remain elevated after CK normalizes, or if cholestatic enzymes (alkaline phosphatase, bilirubin) are disproportionately elevated. 3