Do Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) levels increase in patients with rhabdomyolysis?

AST and ALT Elevation in Rhabdomyolysis

Yes, AST and ALT are typically elevated in rhabdomyolysis, with AST showing more significant elevation than ALT due to its higher concentration in skeletal muscle. 1, 2

Patterns of Aminotransferase Elevation in Rhabdomyolysis

Frequency and Magnitude

• AST elevation is extremely common in rhabdomyolysis, occurring in approximately 93% of patients with CPK ≥1,000 U/L 2
• ALT elevation is less common but still prevalent, occurring in about 75% of patients with rhabdomyolysis 2
• AST tends to be more significantly elevated than ALT, creating an AST-dominant pattern 3
• The elevation can be substantial, with some cases showing aminotransferase levels exceeding 1,000 IU/L 4

Source of Elevation

• The elevated aminotransferases in rhabdomyolysis primarily originate from damaged skeletal muscle, not from liver injury 1, 2
• AST is present in higher concentrations in skeletal muscle than ALT, explaining the AST-dominant pattern typically seen 3
• This pattern differs from most primary liver diseases where ALT is often more elevated or equal to AST (except in alcoholic liver disease) 5, 6

Clinical Correlation and Monitoring

Relationship with CPK

• AST levels tend to decrease in parallel with CPK during recovery from rhabdomyolysis, further supporting skeletal muscle as the source 2
• ALT levels do not show the same parallel decrease with CPK 2

Diagnostic Challenges

• The elevation of aminotransferases in rhabdomyolysis can lead to unnecessary liver investigations, including liver biopsy 1
• Standard liver function tests lack tissue specificity to distinguish primary liver injury from muscle injury 1, 7
• When evaluating elevated aminotransferases, it's crucial to consider rhabdomyolysis first in patients with suspected skeletal muscle injury 3

Distinguishing Liver Injury from Muscle-Derived Enzyme Elevation

Key Differentiating Features

• AST:ALT ratio can help differentiate the source:
  • Rhabdomyolysis typically shows AST > ALT 2, 3
  • Alcoholic liver disease typically shows AST:ALT ratio >2 5, 6
  • Viral hepatitis and other non-alcoholic liver diseases typically show AST:ALT ratio closer to 1:1 6

Advanced Biomarkers

• Serum microRNA-122 (miR-122) shows promise as a more liver-specific biomarker
• miR-122 is elevated in only about 34% of patients with acute skeletal muscle injury compared to 100% of patients with acute liver injury 7
• miR-122 may be particularly useful in cases where both rhabdomyolysis and potential liver injury coexist, such as in recreational drug use 7

Clinical Implications

Prognostic Significance

• Patients with rhabdomyolysis who have significantly elevated aminotransferases (>1,000 IU/L) may have higher mortality rates than those with lower aminotransferase levels 4
• However, this likely reflects more severe overall disease rather than primary liver injury

Management Considerations

• When elevated aminotransferases are found in the setting of confirmed rhabdomyolysis, extensive liver investigations may not be necessary unless there are other signs of liver dysfunction 1, 3
• Focus should remain on treating the underlying cause of rhabdomyolysis and preventing complications like acute kidney injury

Understanding that aminotransferase elevations in rhabdomyolysis primarily reflect muscle damage rather than liver injury can help avoid unnecessary diagnostic procedures while ensuring appropriate management of these patients.