Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 14, 2020; 26(10): 1020-1028
Published online Mar 14, 2020. doi: 10.3748/wjg.v26.i10.1020
Abnormal liver function tests associated with severe rhabdomyolysis
Andy KH Lim
Andy KH Lim, Department of General Medicine, Monash Health, Clayton VIC 3168, Australia
Andy KH Lim, Department of Medicine, School of Clinical Sciences, Monash University, Clayton VIC 3168, Australia
Author contributions: Lim AKH conceptualized and wrote the paper.
Conflict-of-interest statement: I have no potential conflict of interest to declare and have not received funding support for this work.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Andy KH Lim, MBBS, FRACP, MMed(ClinEpi), PhD, Senior Lecturer, Staff Physician, Department of General Medicine, Monash Health, and Department of Medicine, School of Clinical Sciences, Monash University, 246 Clayton Road, Clayton VIC 3168, Australia.
Received: October 28, 2019
Peer-review started: October 28, 2019
First decision: December 12, 2019
Revised: January 6, 2020
Accepted: March 9, 2020
Article in press: March 9, 2020
Published online: March 14, 2020

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.