The impact of COVID-19 on the clinical outcome of patients with cirrhosis deserves more attention and research

Abstract

High rates of 30-day mortality in patients with cirrhosis and COVID-19Journal of HepatologyVol. 73Issue 5PreviewCoronavirus disease 2019 (COVID-19) poses a major health threat to healthy individuals and those with comorbidities, but its impact on patients with cirrhosis is currently unknown. Herein, we aimed to evaluate the impact of COVID-19 on the clinical outcome of patients with cirrhosis. Full-Text PDF Reply to: Correspondence on “High rates of 30-day mortality in patients with cirrhosis and COVID-19”Journal of HepatologyVol. 73Issue 6PreviewWe read with interest the letters by Gao et al. and Medhat et al. on our recently published paper reporting data on the impact of COVID-19 on cirrhotic patients in an Italian multicentre cohort.1 Full-Text PDF We read with interest the paper “High rates of 30-day mortality in patients with cirrhosis and COVID-19” by Iavarone et al. in Journal of Hepatology.[1]Iavarone M. D'Ambrosio R. Soria A. Triolo M. Pugliese N. Del Poggio P. et al.High rates of 30-day mortality in patients with cirrhosis and COVID-19.J Hepatol. 2020; Google Scholar In the article, the authors report that COVID-19 is associated with elevated 30-day mortality in cirrhotic patients. After carefully reading, we wish to put forth the following suggestions. First, there were 4 predictor variables (MELD, delta-MELD, CLIF-OF, and moderate/severe respiratory failure) with 17 fatal outcome events in the multivariate Cox model. The rule of thumb is that logistic and Cox models should be used with a minimum of 10 events per predictor variable (EPV). Previous results showed increasing bias and variability, unreliable confidence interval coverage, and problems with model convergence as EPV declined below 10 and especially below 5.[2]Concato J. Peduzzi P. Holford T.R. Feinstein A.R. Importance of events per independent variable in proportional hazards analysis. I. Background, goals, and general strategy.J Clin Epidemiol. 1995; 48: 1495-1501Abstract Full Text PDF PubMed Scopus (531) Google Scholar,[3]Peduzzi P. Concato J. Feinstein A.R. Holford T.R. Importance of events per independent variable in proportional hazards regression analysis. II. Accuracy and precision of regression estimates.J Clin Epidemiol. 1995; 48: 1503-1510Abstract Full Text PDF PubMed Scopus (1317) Google Scholar Therefore, a larger sample size is needed to validate the results of this study. Second, it might be reasonable to use logistic regression, with the outcome being a dichotomous status (alive or dead) since the relative granularity of time is low (a short-term follow-up: 30 days). Third, the authors report that patients with cirrhosis had increased MELD and CLIF-OF scores at COVID-19 diagnosis. However, most patients (80%) with COVID-19 in the cohort received thromboprophylaxis, which would affect the results of prothrombin time (PT) and international normalized ratio (INR). Prolonged PT and high INR levels would result in higher MELD, Child-Pugh and CLIF-OF scores. Finial, previous studies found that ACE2 internalization by SARS-CoV-2 would potentially result in the loss of ACE2 activity at the cell surface and voids a key pathway of angiotensin (Ang)-II metabolism and Ang-(1-7) generation.[4]South A.M. Diz D.I. Chappell M.C. COVID-19, ACE2, and the cardiovascular consequences.. 2020; 318: H1084-H1090Google Scholar,[5]Li Y.C. Bai W.Z. Hashikawa T. The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients.J Med Virol. 2020; Crossref Scopus (68) Google Scholar Experimentally, Ang-(1–7) inhibits liver fibrogenesis and exerts natriuretic and portal hypotensive effects.[6]Sansoè G. Aragno M. Wong F. Pathways of hepatic and renal damage through non-classical activation of the renin-angiotensin system in chronic liver disease.Liver Int. 2020; 40: 18-31Crossref PubMed Scopus (24) Google Scholar The reduction in ACE2 by SARS-CoV-2-induced internalization would be predicted to aggravate liver fibrosis and portal hypertension, and exacerbate disease severity, especially in the long-term. Therefore, the impact of COVID-19 on the long-term liver-related outcomes in patients with cirrhosis deserves attention. The authors received no financial support to produce this manuscript. Study concept and design: Feng Gao, Zhi-Ming Huang; Drafting of the manuscript: Feng Gao; Study supervision: Zhi-Ming Huang. All authors contributed to the manuscript for important intellectual contents and approved the submission. All authors: nothing to declare. Please refer to the accompanying ICMJE disclosure forms for further details. Download .pdf (.15 MB) Help with pdf files disclosures.pdf