Is transaminitis (elevated liver enzymes) in rhabdomyolysis from a muscle source?

Transaminitis in Rhabdomyolysis: Muscle Origin of Elevated Liver Enzymes

Yes, elevated liver enzymes (transaminitis) in rhabdomyolysis are primarily from muscle source rather than actual liver injury. Skeletal muscle breakdown releases intracellular enzymes including aspartate aminotransferase (AST) and alanine aminotransferase (ALT) into the circulation, mimicking liver damage.

Mechanism of Transaminitis in Rhabdomyolysis

• Rhabdomyolysis is characterized by skeletal muscle injury with release of intracellular constituents into the circulation, including enzymes that are traditionally associated with liver function 1
• During muscle breakdown, muscle-derived AST and ALT are released into the bloodstream, causing elevations that can be misinterpreted as liver injury 1
• These enzymes lack tissue specificity, making it difficult to distinguish between primary liver injury and muscle-derived enzyme elevations 1

Clinical Characteristics of Muscle-Derived Transaminitis

• In rhabdomyolysis, AST elevations are typically higher than ALT elevations, which differs from the pattern seen in primary liver injury 1
• Transaminase elevations correlate with creatine kinase (CK) levels, supporting their muscle origin 2
• Transaminitis can be severe, with enzyme levels reaching hundreds or thousands of times the upper limit of normal in cases of significant muscle breakdown 3

Distinguishing Muscle-Derived from Liver-Derived Transaminitis

• Concurrent marked elevation of CK (often >5 times upper limit of normal) suggests muscle as the source of transaminase elevation 2
• The AST:ALT ratio is typically higher in muscle-derived transaminitis than in primary liver injury 1
• Absence of other liver function abnormalities (normal bilirubin, alkaline phosphatase, and coagulation studies) supports muscle rather than liver origin 1
• Transaminitis typically resolves as CK levels normalize during recovery from rhabdomyolysis 3

Clinical Implications

• Recognizing the muscle origin of transaminitis in rhabdomyolysis can prevent unnecessary liver investigations, including liver biopsy 1
• In patients with rhabdomyolysis and elevated liver enzymes, clinicians should first consider muscle as the source before pursuing extensive hepatic workup 1
• Monitoring transaminase levels alongside CK can help confirm their muscle origin as both should decline in parallel during recovery 3

Special Considerations

• In some cases, true hepatic injury may coexist with rhabdomyolysis due to shared mechanisms such as ischemia or toxin exposure 1
• Patients with underlying liver disease may have exacerbation of their condition during episodes of rhabdomyolysis 1
• In cases of statin-induced rhabdomyolysis, distinguishing between drug-induced liver injury and muscle-derived transaminitis is particularly important 4

Common Pitfalls

• Misattributing muscle-derived transaminitis to liver disease can lead to unnecessary diagnostic procedures 1
• Failure to recognize the muscle origin of transaminitis may delay appropriate management of rhabdomyolysis 5
• The absence of myoglobinuria does not exclude rhabdomyolysis as a cause of transaminitis, as myoglobin may be negative in up to 81% of cases despite significant muscle breakdown 2

By understanding that transaminitis in rhabdomyolysis primarily reflects muscle enzyme release rather than liver injury, clinicians can avoid unnecessary hepatic investigations and focus on appropriate management of the underlying muscle damage.