key: cord-0991988-tmwvojiv
authors: Yang, Haiyan; Xu, Jie; Liang, Xuan; Shi, Li; Wang, Yadong
title: Chronic liver disease independently associated with COVID-19 severity: evidence based on adjusted effect estimates
date: 2021-01-28
journal: Hepatol Int
DOI: 10.1007/s12072-020-10133-y
sha: d0c671b3caabcf5f281bd9e98a3069181608afd0
doc_id: 991988
cord_uid: tmwvojiv

nan

without sufficient data were excluded. The heterogeneity was detected by I 2 statistics. The pooled effect sizes with 95% confidence interval (CI) were estimated. Publication bias was evaluated by Begg's test and Egger's test. Sensitivity analysis, subgroup analysis and meta-regression analysis were also performed. All data were analyzed using Stata 12.1. p < 0.05 was considered statistical significance. Figure S1 shows the flow diagram of study selection. 29 articles with 90,095 confirmed COVID-19 patients were included. The characteristics of the included studies are summarized in Table 1 . Our meta-analysis based on adjusted effect estimates demonstrated that COVID-19 patients with chronic liver disease tended to develop severe outcome compared to those without (pooled effect size = 1.52, 95% CI: 1.14-2.02, Fig. 1a ) and had a significantly increased risk for mortality compared to those without (pooled effect size = 1.36, 95% CI: 1.22-1.53, Fig. 1b) . Sensitivity analysis exhibited that our findings were stable (Fig. 1c) . Subgroup analyses by sample size and study design exhibited consistent results (Table S1 and Figure S2 -3). But inconsistent results were observed in subgroup analyses by age, male percentage, effect estimate and region (Table S1 and Figure S4-7) . Meta-regression analysis showed that the tested variables such as sample size, age, male percentage, effect estimate, study design and region might not be the source of heterogeneity (Table S1 ). Begg's test and Egger's test suggested that there might be potential publication bias ( Figure S8 ).

This meta-analysis has several limitations. First, inconsistent results were observed in subgroup analyses by age, male percentage and region. Thus, the findings should be cautiously extrapolated to whole population. Second, most of the included studies are retrospective, further welldesigned studies with more prospective literatures are warranted to confirm our findings. Third, publication bias might The forest plot on the association between chronic liver disease and COVID-19 mortality; c Leave-one-out sensitivity analysis indicated that our results were stable and robust. *Indicates that the combined value was calculated on the basis of subgroups exist although we tried to search potential articles in electronic databases. In summary, our study indicated that chronic liver disease was independently associated with COVID-19 severity and mortality, especially among aged individuals, male-dominated population, USA and Europe. Proper management of COVID-19 patients with chronic liver disease is highly recommended to prevent severe situations and mortality.

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We would like to thank Ying Wang, Hongjie Hou, Peihua Zhang, Yang Li, Jian Wu and Wenwei Xiao (All are from Department of Epidemiology, School of Public Health, Zhengzhou University, Zhengzhou 450001, China) for their kind help in searching articles and collecting data, and valuable suggestions for data analysis. 

Conflict of interest The authors Haiyan Yang, Jie Xu, Xuan Liang, Li Shi and Yadong Wang have no any potential conflict of interest regarding this submitted manuscript.