key: cord-0830080-5nas1xb5
authors: Grace, Josephine A.; Casey, Stephen; Burrell, Louise M.; Angus, Peter W.
title: Proposed mechanism for increased COVID-19 mortality in patients with decompensated cirrhosis
date: 2020-09-04
journal: Hepatol Int
DOI: 10.1007/s12072-020-10084-4
sha: 25b05d68fd95cb6ef503f328fb8f0b02d51306ac
doc_id: 830080
cord_uid: 5nas1xb5

nan

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 cirrhotic liver may make it subsequently more vulnerable to angiotensin II-mediated injury.

This hypothesis raises interesting questions regarding possible therapeutic interventions. Emerging observational data suggest that ACE inhibitors and angiotensin-receptor blockers do not increase risk in COVID-19 [10] , and we await with interest data forthcoming from therapeutic trials. These drugs, however, are poorly tolerated in patients with advanced liver disease associated with a hyperdynamic circulation, where they commonly cause renal compromise. Further studies elucidating the role the RAS plays in liver injury due to SARS-CoV-2 and the excess mortality in patients with cirrhosis may lead to novel therapeutic targets.

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