Cardiac and Muscle Injury Might Partially Contribute to Elevated Aminotransferases in COVID-19 Patients
Authors: Yongxing Xu, Jianwen Gu
Journal: Clinical Gastroenterology and Hepatology (2020)

Corona virus disease 2019 (COVID-19) patients can have elevated aminotransferases.1Fan Z. et al.Clin Gastroenterol Hepatol. 2020; (Epub 2020/04/14)Google Scholar, 2Guan W.J. et al.N Engl J Med. 2020; (Epub 2020/02/29)Google Scholar, 3Wang D. et al.JAMA. 2020; (Epub 2020/02/08)Google Scholar It seemed that increases of aspartate aminotransferase were more prominent than alanine aminotransferase in COVID-19 patients according to previous studies.1Fan Z. et al.Clin Gastroenterol Hepatol. 2020; (Epub 2020/04/14)Google Scholar, 2Guan W.J. et al.N Engl J Med. 2020; (Epub 2020/02/29)Google Scholar, 3Wang D. et al.JAMA. 2020; (Epub 2020/02/08)Google Scholar In the study by Fan et al,1Fan Z. et al.Clin Gastroenterol Hepatol. 2020; (Epub 2020/04/14)Google Scholar the proportions of patients with elevated aspartate aminotransferase and alanine aminotransferase were 21.6% and 18.2%, respectively. Among severe COVID-19 patients, the proportion of patients with elevated levels of aspartate aminotransferase also seemed higher than the proportion with elevated levels of alanine aminotransferase (39.4% vs 28.1%) in the study by Guan et al.2Guan W.J. et al.N Engl J Med. 2020; (Epub 2020/02/29)Google Scholar In another study,3Wang D. et al.JAMA. 2020; (Epub 2020/02/08)Google Scholar the absolute levels of aspartate aminotransferase were also higher than alanine aminotransferase (31 vs 24 U/L). Of note, the upper limits of normal for aspartate aminotransferase and alanine aminotransferase were different, which were 40 vs 50 U/L, respectively.3Wang D. et al.JAMA. 2020; (Epub 2020/02/08)Google Scholar But not all abnormal liver function test results mean liver damage. Guo et al4Guo T. et al.JAMA Cardiology. 2020; (Epub 2020/03/29)Google Scholar indicated that acute cardiac injury can occur in COVID-19 patients, which can be seen in up to 27.8% of patients (52/187). Patients with acute cardiac injury also had significantly higher levels of aspartate aminotransferase than those without cardiac injury (39.5 vs 29.0 U/L; P < .001). However, the difference in alanine aminotransferase did not reach statistical significance between patients with acute cardiac injury and without it (28.5 vs 23.0; P = .11).4Guo T. et al.JAMA Cardiology. 2020; (Epub 2020/03/29)Google Scholar Meanwhile, the heart may occasionally contain a high alanine aminotransferase activity,5Giesen P.L. et al.Clin Chem. 1989; 35: 279-283Crossref PubMed Scopus (25) Google Scholar so abnormal levels of alanine aminotransferase and aspartate aminotransferase might partly result from myocardial injury, especially when increases of aspartate aminotransferase are more prominent. In addition, the viral infection can cause muscle injury. In the case of muscle injury, sarcoplasmic proteins including creatine kinase, alanine aminotransferase, and aspartate aminotransferase can be high. It has been reported that rhabdomyolysis can occasionally occur in COVID-19 patients.2Guan W.J. et al.N Engl J Med. 2020; (Epub 2020/02/29)Google Scholar,6Jin M. et al.Emerging Infectious Diseases. 2020; 26 (Epub 2020/03/21)Google Scholar Hence, we think the incidence of liver damage might be overestimated in COVID-19 patients. We speculate that cardiac and muscle injury might partially contribute to elevated aminotransferases in COVID-19 patients. The largest study so far found that 13.7% of COVID-19 patients had elevated levels of creatine kinase, which may also indicate that muscle or cardiac injury occurred.2Guan W.J. et al.N Engl J Med. 2020; (Epub 2020/02/29)Google Scholar Regarding the association between liver injury and overall prognosis in COVID-19 patients, Fan et al1Fan Z. et al.Clin Gastroenterol Hepatol. 2020; (Epub 2020/04/14)Google Scholar indicated that baseline liver impairment was associated with a prolonged hospital stay, and abnormal liver function during admission had little effect on the length of hospital stay. However, the acute cardiac injury is significantly associated with fatal outcome in COVID-19 patients4Guo T. et al.JAMA Cardiology. 2020; (Epub 2020/03/29)Google Scholar; meanwhile, rhabdomyolysis is a potentially life-threatening condition. We suggest that patients with elevated aminotransferase be evaluated for the presence of acute cardiac injury or rhabdomyolysis. The authors thank all the medical workers and scientists who are battling for days and nights to eradicate this epidemic. ReplyClinical Gastroenterology and HepatologyVol. 19Issue 2PreviewWe appreciate Xu et al for the external validation of the NASH PT score that we developed for identifying nonalcoholic steatohepatitis (NASH) among the diverse spectra of nonalcoholic fatty liver disease (NAFLD).1 The NASH PT score is a polygenic risk scoring model incorporating 2 genetic risk factors, PNPLA3 rs738409 and TM6SF2 rs58542926. We developed it from the biopsy-proven NAFLD cohort (n = 302) and validated it using an independent replication dataset (n = 151).1 The area under the receiver operating characteristic curve in the replication cohort was 0.787 (95% confidence interval, 0.715–0.860), which was significantly better than the NASH score based on only 1 single-nucleotide polymorphism, PNPLA3 rs738409. Full-Text PDF ReplyClinical Gastroenterology and HepatologyVol. 18Issue 12PreviewWe thank Chen and Zhou,1 Lv et al,2 and Ye and Song3 for the comments on our study. We did not apply the definition of drug-induced liver injury from the European Association for the Study of the Liver Clinical Practice Guidelines in our study because the exact mechanism of COVID-19-related liver damage is still unclear (eg, a drug, the virus itself, immune response, or a mixture). We defined COVID-19-related liver injury based on elevation in any 1 of the 5 (not 6) parameters including alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), alkaline phosphatase (ALP), and total bilirubin. Full-Text PDF