Letter to the Editor: Coronavirus Disease 2019–Related Liver Injury and Clinical Outcomes: Does It Really Exist?

TO THE EDITOR:

We read with interest the study by Lei and colleagues on the association between markers of liver injury and mortality in coronavirus disease 2019 (COVID‐19) in China.^{( 1 )} The authors have painstakingly collated data from a large number of patients with COVID‐19 from multiple centers across Wuhan. They found that an increase in aspartate aminotransferase (AST) and its dynamicity correlated with COVID‐19‐related liver injury and patient outcomes. They concluded that the dynamic patterns of liver injury indicators, represented by AST, correspond with COVID‐19‐related liver injury. A basic understanding of enzymes that form part of the liver test is fundamental to the interpretation of clinical events. Alanine aminotransferase (ALT) produced in the hepatocytes is a very specific marker of liver cell injury, with relatively lower concentrations in other organ tissues. The rise in ALT may occur with the use of specific drugs, such as antibiotics and glucocorticoids. AST, on the other hand, occurs in two isoforms, indistinguishable on standard assays. It is the mitochondrial isoenzyme, which is produced by the hepatocyte, that reacts to membrane damage similar to ALT, whereas the cytosolic isoenzyme is produced by cells of skeletal muscles, cardiac myocytes, and renal tissue. The use of AST in isolation is not recommended as a marker for hepatocellular injury.^{( 2 )} The conclusion inculpating AST with COVID‐19 liver injury is inaccurate and factually related to the evolving multiorgan dysfunction (MOD). This is underscored by the fact that most patients had already developed cardiac and renal injury before the development of proposed acute liver injury (ALI) at 10‐15 days after admission, further exacerbated by antibiotics and glucocorticoids. AST and ALT levels were significantly high in those with lymphocytopenia, a marker of severe COVID‐19.^{( 3 )} Scoring systems for MOD were not used by the authors, adding to the confounding. The definition of ALI in the current study is flawed. An important criterion for diagnosing ALI in those without preexisting liver disease is an international normalized ratio >2.^{( 4 )} The current study does not incorporate appropriate methods to clearly identify synthetic and metabolic hepatocellular dysfunction. The term “COVID‐19‐related liver injury” is perchance misleading, akin to the recently described COVID‐19 involvement of the pancreas.^{( 5 )}