To the Editor:
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 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 , 3 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 , 5 Experimentally, Ang-(1–7) inhibits liver fibrogenesis and exerts natriuretic and portal hypotensive effects.6 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.
Financial support
The authors received no financial support to produce this manuscript.
Authors' contributions
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.
Conflict of interest
All authors: nothing to declare.
Please refer to the accompanying ICMJE disclosure forms for further details.
Footnotes
Supplementary data to this article can be found online at https://doi.org/10.1016/j.jhep.2020.06.024.
Supplementary data
References
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