Aspartate aminotransferase: A prognostic marker rather than a specific liver injury marker in COVID-19
Authors: Gerui Li
Journal: Journal of Infection (2020)

We read with interest the study by Kunutsor and Laukkanen on the markers of liver injury and clinical outcomes in coronavirus disease 2019 (COVID-19) patients.1Kunutsor Setor K. Laukkanen Jari A Markers of liver injury and clinical outcomes in COVID-19 patients: a systematic review and meta-analysis.J Infect. 2020; https://doi.org/10.1016/j.jinf.2020.05.045Google Scholar The authors conducted a systematic review and meta-analysis of sixteen retrospective cohort studies based in China and concluded that elevated admission levels of markers of liver injury particularly the aminotransferases, may be associated with progression to severe disease or death in COVID-19. One interesting finding is that much larger effect sizes were observed in aspartate aminotransferase (AST) compared to alanine aminotransferase (ALT) in association with both severe illness (risk ratio 2.09 (0.44–9.9) vs 1.03 (0.23–2.15); mean difference 12.60 U/L (8.43, 16.77) vs 9.15 U/L (1.47, 16.82)) and mortality (risk ratio 10.42 (7.05–15.40) vs 3.35 (2.37–4.75); mean difference 17.13 U/L (11.25, 23.01) vs 5.82 U/L (−2.57, 14.21)). These data suggest that AST may serve as a better prognostic marker of COVID-19 compared to ALT. However, it is important to stress that AST is considered a less specific marker for liver injury than ALT. ALT is produced in the hepatocytes with relatively lower expression in other organs. In contrast, AST has two isoforms, the mitochondrial isoenzyme produced by the hepatocyte, and the cytosolic isoenzyme produced by cells of other tissues, such as brain, myocardial cells and skeletal muscle cells. The two isoforms cannot be distinguished in regular liver function test.2Qian Xu Trefor Higgins Cembrowski George S Limiting the testing of AST: a diagnostically nonspecific enzyme.Am J Clin Pathol. 2015; Google Scholar Thus, misinterpretation of AST data may lead to an overestimation on the incidence of liver injury in COVID-19 patients. Indeed, the association of AST levels with severe illness or mortality probably involves the development of multi-organ impairment, which is common in severe and death cases of COVID-19.3Fei Zhou Ting Yu Ronghui Du Guohui Fan Ying Liu Zhibo Liu et al.Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.Lancet. 2020; https://doi.org/10.1016/S0140-6736(20)30566-3Abstract Full Text Full Text PDF PubMed Scopus (18518) Google Scholar,4Dawei Wang Bo Hu Chang Hu Fangfang Zhu Xing Liu Jing Zhang et al.Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China.JAMA - J Am Med Assoc. 2020; https://doi.org/10.1001/jama.2020.1585Crossref Scopus (16034) Google Scholar Furthermore, the association between markers of liver injury and outcomes of COVID-19 is further confounded by in-hospital medications such as antibiotics, antiviral agents, and glucocorticoids. Unfortunately, none of the included studies in this systematic review and meta-analysis properly adjusted or matched these potential confounders. Thus, the actual incidence of liver injury (as usually indicated by the changes of markers such as ALT and AST) and the degree of its contribution to the development of severe illness and death remain unclear. Taken together, markers of liver injury especially AST should be considered as a prognostic marker rather than a specific marker of liver injury in COVID-19 patients. Cautions must be taken when interpreting these data. None. This work did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.