Can the elevation of AST and ALT in my patient with rhabdomyolysis be related to the muscle injury itself?

Yes! Elevated serum AST and ALT in the setting of rhabdomyolysis is not uncommon and, at least in some cases, appears to be related to the skeletal muscle injury itself.1,2

In a study of 16 patients considered to have significant muscle necrosis due to extreme exercise, polymyositis or seizures without evidence of liver disease (eg, viral hepatitis, exposure to hepatotoxic drugs, heart failure, biliary tract disease, recent hypotension) AST and, to lesser degree, ALT was elevated. For extreme exercise, the median AST and ALT concentrations were 2,466 IU/L and 497 U/L, respectively, while for seizures these levels were 1,448 U/L and 383 U/L respectively.1  

Another study reported AST elevation (>40 U/L) in 93.1% of patients with rhabdomyolysis and ALT elevation (>40 U/L) in 75.0% of patients with serum creatine kinase ≥1000 U/L. Further supporting a skeletal muscle origin for AST elevation was the finding that AST concentrations fell in parallel with CK drop during the first 6 days of hospitalization for rhabdomyolysis. It was posited that ALT concentrations dropped slower because of its longer serum half-life (47 hours vs 17 hours for AST).2 Despite these findings, concurrent liver injury as an additional source of AST or ALT elevation cannot be excluded.

Elevation of AST and ALT with muscle injury should not come as a surprise. AST is found in heart and skeletal muscle among many other organs. Even ALT which is considered more specific to liver is found in organs such as skeletal muscle, heart and kidney, though at lower concentrations.3

Bonus Pearl: Did you know that the first description of rhabdomyolysis in the literature involved English victims of crush injuries during World War II?2

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References

  1. Nathwani RA, Pais S, Reynolds TB, et al. Serum alanine aminotransferase in skeletal muscle diseases. Hepatology 2005;41:380-82. https://www.ncbi.nlm.nih.gov/pubmed/15660433
  2. Weibrecht K, Dayno M, Darling C, et al. Liver aminotransferases are elevated with rhabdomyolysis in the absence of significant liver injury. J Med Toxicol 2010;6:294-300. https://link.springer.com/article/10.1007%2Fs13181-010-0075-9
  3. Giannini EG, Testa R, Savarino V. Liver enzyme alteration: a guidance for clinicians. CMAJ2005;172:367-79. Giannini EG, Testa R, Savarino V. Liver enzyme alteration: a guidance for clinicians. CMAJ 2005;172:367-79. https://www.ncbi.nlm.nih.gov/pubmed/15684121
Can the elevation of AST and ALT in my patient with rhabdomyolysis be related to the muscle injury itself?

Why is serum AST levels generally higher than ALT in alcohol-induced liver injury?

Alcohol is thought to cause injury to the mitochondria which contains AST but not ALT. In addition, in chronic alcoholics, pyridoxine (vitamin B6) deficiency may reduce the synthesis of ALT more than AST because the former is more B6-dependent (1).  

AST/ALT ratio >1 may be more common in advanced alcohol liver disease (e.g. cirrhosis) than in the setting of high alcohol consumption without severe liver disease (2). 

Also, remember that AST levels greater than 500 U/L and ALT levels greater than 300 U/L are uncommon in alcohol-related liver injury.  In this setting, other causes such as acetaminophen toxicity should be excluded (1).

Referemces

1. Johnston DE. Special considerations in interpreting liver function tests. Am Fam Physician1999;59:2223-30.  https://www.ncbi.nlm.nih.gov/pubmed/10221307  

2. Nyblom H, Berggren U, Balldin J, et al. High AST/ALT ratio may indicate advanced alcoholic liver disease rather than heavy drinking. Alcohol &Alcoholism 2004;39:336-39. https://www.ncbi.nlm.nih.gov/pubmed/15208167

Why is serum AST levels generally higher than ALT in alcohol-induced liver injury?