Abnormal liver function tests associated with severe rhabdomyolysis

Abstract

Rhabdomyolysis is a syndrome of skeletal muscle injury with release of cellular constituents such as potassium, phosphate, urate and intracellular proteins such as myoglobin into the circulation, which may cause complications including acute kidney injury, electrolyte disturbance and cardiac instability. Abnormal liver function tests are frequently observed in cases of severe rhabdomyolysis. Typically, there is an increase in serum aminotransferases, namely aspartate aminotransferase and alanine aminotransferase. This raises the question of liver injury and often triggers a pathway of investigation which may lead to a liver biopsy. However, muscle can also be a source of the increased aminotransferase activity. This review discusses the dilemma of finding abnormal liver function tests in the setting of muscle injury and the potential implications of such an association. It delves into some of the clinical and experimental evidence for correlating muscle injury to raised aminotransferases, and discusses pathophysiological mechanisms such as oxidative stress which may cause actual liver injury. Serum aminotransferases lack tissue specificity to allow clinicians to distinguish primary liver injury from muscle injury. This review also explores potential approaches to improve the accuracy of our diagnostic tools, so that excessive or unnecessary liver investigations can be avoided.

Keywords: Rhabdomyolysis; Muscle; Creatine kinase; Liver function tests; Alanine aminotransferase; Aspartate aminotransferase; Aminotransferases

Core tip: There is observational and experimental data demonstrating that serum alanine and aspartate aminotransferases can be elevated in patients with rhabdomyolysis due to muscle release of these enzymes, and cause confusion with liver disease. Clinicians should firstly appreciate this association exists and secondly, understand the typical pattern and trajectory of the levels of creatine kinase and aminotransferases in the setting of rhabdomyolysis. An atypical trajectory, concurrently elevated bilirubin or γ-glutamyl transferase, or serum alanine aminotransferase levels above 800 U/L are inconsistent with isolated muscle injury as the cause of the elevated aminotransferases, and further investigation for liver disease may be warranted.