key: cord-0682377-6w70mh6l
authors: Qi, Xiaolong; Liu, Chuan; Jiang, Zicheng; Gu, Ye; Zhang, Guo; Shao, Chuxiao; Yue, Hongmei; Chen, Zhenhuai; Ma, Baoyi; Liu, Dengxiang; Zhang, Lin; Wang, Jitao; Xu, Dan; Lei, Junqiang; Li, Xun; Huang, Huihong; Wang, Yan; Liu, Hongyan; Yang, Jie; Pan, Hongqiu; Liu, Weiying; Wang, Wenjuan; Li, Fujian; Zou, Shengqiang; Zhang, Hongguang; Dong, Jiahong
title: Multicenter analysis of clinical characteristics and outcome of COVID-19 patients with liver injury
date: 2020-04-17
journal: J Hepatol
DOI: 10.1016/j.jhep.2020.04.010
sha: 53e8b5b00fbdb5f0a1e04da870295f50f3b1ae11
doc_id: 682377
cord_uid: 6w70mh6l

nan

To the Editor: The coronavirus disease 2019 (COVID-19) has become a global challenge since the December 2019. 1 We read with interest the paper "Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study", in which 43 (43.4%) of 99 patients had differing degrees of liver function abnormality; One patient had severe liver function damage (alanine aminotransferase [ALT] 7590 U/L, aspartate aminotransferase [AST] 1445 U/L). 1 For patients with COVID-19 in intensive care unit care, liver function was significantly worse than those in non-intensive care unit care. 2 The similar features was further reported in a study of 138 hospitalized patients in Wuhan, China. 3 On the basis of these clinical findings, liver injury in COVID-19 attracted widespread concern. 4 There is no data yet focusing on the clinical characteristics and outcome of COVID-19 patients with liver injury.

In the multicenter cohort (COVID-LIVER-CHESS) of 9 designated hospitals in China, patients with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and without pre-existing liver-related comorbidities were consecutively enrolled from January 23, 2020 to February 18, 2020, with final follow-up on March 19, 2020. We defined liver injury as any parameter more than the upper limit of normal value of ALT (40 U/L), AST (40 U/L), and total bilirubin (TBil, 17.1 µmol/L) on admission.

Also, we defined the degree of severity of COVID-19 (severe vs. nonsevere) at the time of admission. 5 During hospitalization, most patients received antiviral treatment with interferon inhalation, lopinavir and ritonavir, combined with probiotics. Patients were discharged once the results of two real-time fluorescence polymerase-chain-reaction tests taken 24 hours apart were negative for SARS-CoV-2. This study was approved by ethics commissions, with a waiver of written informed consent. Leukopenia and lymphopenia occurred in 7 (21.88%) and 5 (15.63%) patients, respectively.

There were elevated blood levels for C-reactive protein in 21 (65.63%) patients with liver injury ( Table 1) . Chest images showed abnormal findings including ground-glass opacity in the lungs of 31 (96.88%) patients. Notably, the time from illness onset to admission of COVID-19 patients was correlated with the risk of liver injury (Figure 1B) . For those with liver injury, the time from onset to admission was significantly longer than that of cases without liver injury (8.00 [IQR, 5.00-10.00] vs 5.00 [IQR, 4.00-9.00]; P=0.037, Figure 1C ). Figure 1D ).

In the COVID-LIVER-CHESS study, we analyzed the clinical characteristics and outcome of multicenter patients with COVID-19 related liver injury for the first time, to our best knowledge. Notably, COVID-19 involves in not only respiratory system, but also digestive system. [4] [5] [6] Diarrhea occurred in 42 (3.8%) of 1,099 patients in China, 5 and 43 (43.4%) of 99 patients had differing degrees of liver function abnormality. 1 On the basis of an unbiased evaluation of cell type specific expression of angiotensin converting enzyme 2 (ACE2) using single cell RNA-seq data, it indicated that SARS-CoV-2 might directly bind to ACE2 positive cholangiocytes to dysregulate liver function. [7] [8] [9] Liver pathological findings of COVID-19

showed moderate microvascular steatosis, and mild lobular and portal activity, which suggested that the injury could have been caused by either SARS-CoV-2 infection or drug-induced liver injury. 10 might be aggravated. The further study on the mechanism of liver injury in COVID-19 remains needed. In addition, the hospital stay of patients with liver injury was not statistically different compared to that of cases without liver injury, which might result from mild liver injury on admission. Therefore, we recommend dynamic monitoring the liver function of patients with liver injury, especially those in intensive care unit care.

The study was limited by small sample size and lack of dynamic monitoring of liver function during hospitalization. A larger longitudinal cohort is needed to clarify the role of liver injury in the outcome of patients with SARS-CoV-2 infection. In summary, the multicenter analysis presents the clinical characteristics and outcome of COVID-19 patients with liver injury, which has important reference value to offer a better multi-system care.

Continuous variables were expressed as median and interquartile range (IQR). Categorical variables were summarized as counts and percentages. The Mann-Whitney test was used to compare difference of continuous variables between groups. Categorical variables were compared by chi-square test or Fisher's exact test. All levels of significance were set at two-sided 5% level. All analyses were performed using SPSS 20.0 (IBM Corp., Armonk, NY). 

A, the distribution of 9 designed hospitals and the percentage of COVID-19 with liver injury.

B, the locally weighted scatterplot smoothing (LOWESS) approach was used to assess the monotonicity between the time from onset to admission and risk of liver injure. C, the compare of the time from onset to admission between patients with liver injure and patients without liver injure using the Mann-Whitney test. D, the compare of the hospital stay between patients with liver injure and patients without liver injure using the Mann-Whitney test. All levels of significance were set at two-sided 5% level. All analyses were performed using SPSS 20.0 (IBM Corp., Armonk, NY) and R 3.5.3 (R Project for Statistical Computing, Vienna, Austria).

Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China

Liver injury in COVID-19: management and challenges

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Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series

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Specific ACE2 Expression in Cholangiocytes May Cause Liver Damage After 2019-nCoV Infection

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