key: cord-319278-d0rgrmd2
authors: Iavarone, Massimo; D’Ambrosio, Roberta; Lampertico, Pietro
title: Authors’ reply on HIGH RATES OF 30-DAY MORTALITY IN PATIENTS WITH CIRRHOSIS AND COVID-19
date: 2020-08-07
journal: J Hepatol
DOI: 10.1016/j.jhep.2020.08.001
sha: 
doc_id: 319278
cord_uid: d0rgrmd2

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Both letters pointed out the limited sample size of our study, which however had already been acknowledged as a possible limitation in the discussion session of our paper. So far, no studies have been able to enrol significantly larger cohorts of COVID-19 cirrhotics, although data are warranted in order to better characterize the natural history of Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in this setting. However, two recent studies seem to confirm our findings. In fact, a single study conducted in North America enrolling 37 patients has confirmed the high mortality rates of patients with cirrhosis and COVID-19, whilst an ongoing international registry has shown a mortality risk similar to ours in the 103 patients with cirrhosis 2, 3 Gao et al raised some concerns regarding the statistical analysis used to predict mortality, suggesting to perform a logistic regression analysis. The logistic regression analysis confirmed that CLIF-OF (OR 1.77, 95%CI 1.24-2.54, p=0.002) and moderate to severe lung failure (OR 1.86, 95%

1.00-3.44, p=0.048) were the only two independent predictors of mortality.

Gao and colleagues also suggested that Model End-Stage Liver disease (MELD), Child-Pugh-Turcotte (CPT) and CLIF-OF scores might have been influenced by thromboprophylaxis. However, in our study, these scores were calculated at COVID-19 diagnosis, i.e. before thromboprophylaxis was started. As low molecular weight heparin was used in most cases, we do not foresee any 1.219-1.539, p≤0.0001) but neither age nor comorbidies, independently predicted mortality.

Moreover, at multivariate analysis on the 50 patients with cirrhosis and COVID-19 only, the presence of comorbidities did not independently predict mortality.

Finally, we agree that acute on chronic liver failure (ACLF) was not cause of death in the majority of our patients, as respiratory failure accounted for 71% of deaths. However, we demonstrated that the mortality rates were significantly higher in our cohort of cirrhotics than in a control-group of non-cirrhotic patients with COVID-19. Moreover, ACLF at COVID-19 was diagnosed in 14 (28%) patients and both the CLIF-OF and CLIF-C scores independently predicted mortality in our cohort.

These findings suggest that SARS-CoV-2 infection had a precipitating role in compensated cirrhotics in causing MELD and Child-Pugh-Turcotte scores deterioration. Resulting liver failure has been found to be a co-factor in addition to respiratory failure in mortality for these patients. 1 This is not a surprising, given the well-known effects of infections as drivers of liver disease worsening and death in the setting of cirrhosis.

While the real role of interaction between SARS-CoV-2 and ACE-2 receptors in liver cells is far to be elucidated, we agree that long-term effects of SARS-CoV-2 on cirrhosis might deserve attention.

As suggested by EASL recommendations on cirrhotics management during SARS-CoV-2 pandemic, we still need to implement systems allowing for remote management of patients, to prevent their exposure to situations and settings at risk as we have already previously suggested for the management of patients with HCC. 4, 5 J o u r n a l P r e -p r o o f

High rates of 30-day mortality in patients with cirrhosis and COVID-19

Comparison of mortality risk in patients with cirrhosis and COVID-19. compared to cirrhosis anone and COVID-19 alone: a multi-center matched cohort

High mortality rates for SARS-CoV-2 infection in patients with pre-existing chronic liver disease and cirrhosis: Preliminary results from an international registry

Care of patients with liver disease during the COVID-19 pandemic: EASL-ESCMID position paper

Management of hepatocellular carcinoma in the time of COVID-19