Proposed mechanism for increased COVID-19 mortality in patients with decompensated cirrhosis
- PDF / 320,412 Bytes
- 2 Pages / 595.276 x 790.866 pts Page_size
- 113 Downloads / 203 Views
LETTER TO THE EDITOR
Proposed mechanism for increased COVID‑19 mortality in patients with decompensated cirrhosis Josephine A. Grace1,2 · Stephen Casey1,2 · Louise M. Burrell2 · Peter W. Angus1,2 Received: 24 June 2020 / Accepted: 17 August 2020 © Asian Pacific Association for the Study of the Liver 2020
We read with interest the article by Qi et al. on the clinical course of COVID-19 in patients with pre-existing decompensated cirrhosis [1]. We wish to draw attention to a possible contribution of increased hepatic expression of angiotensin converting enzyme 2 (ACE2) and ACE to explain the poor outcomes in these patients. Severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) and the closely related SARS-CoV bind to the ACE2 receptor to enter the target cell. ACE2 is expressed in the liver and it has been postulated that SARS-CoV-2 may bind to ACE2 to directly infect the liver. This is supported by the finding that 14–53% of patients with COVID-19 have evidence of liver dysfunction, which is more marked in patients with severe illness [2]. SARS-CoV-2 has been identified in the liver of patients with SARS and may induce liver cell apoptosis via a caspase-dependent pathway [3]. It is possible that SARS-CoV-2 produces liver injury via a similar mechanism. In addition, while ACE and its product angiotensin II promote vasoconstriction, inflammation and fibrosis, the so-called “alternate arm” of the renin angiotensin system (RAS), consisting of ACE2 and angiotensin-(1–7), has vasodilatory and antifibrotic effects [4]. In respiratory failure due to SARS-CoV-2, receptor binding results in shedding of the ACE2 ectodomain and downregulation of ACE2 activity [5]. Binding of SARS-CoV-2 to ACE2 may lead to unopposed ACE activity and angiotensin II mediated tissue injury [6]. This is supported by the observation that angiotensin II levels are increased in otherwise healthy patients with COVID19 and correlate with viral load [7]. Our work has demonstrated that expression of the “alternate” arm of the RAS is increased in cirrhosis [4]. In healthy * Josephine A. Grace [email protected] 1
Department of Gastroenterology and Hepatology, Austin Health, 145 Studley Road, Heidelberg, VIC 3084, Australia
Department of Medicine and Cardiology, University of Melbourne, Austin Health, Heidelberg, Australia
2
livers, ACE2 is predominantly found in cholangiocytes, but in both experimental and human cirrhosis ACE2 gene expression in markedly upregulated and there is widespread parenchymal expression of ACE2 protein. Moreover, we have previously reported that patients with decompensated cirrhosis have increased circulatory ACE2 enzyme (and Ang-(1–7) levels) compared to compensated cirrhotics [8]. We have also shown that ACE activity and angiotensin II levels are increased in cirrhosis [9]. We propose that increased liver parenchymal expression of ACE2 in patients with cirrhosis, and particularly those with decompensated cirrhosis, facilitates entry of virus into the host. Furthermore, upregulated ACE activity in the cirrh
Data Loading...
