Liver Injury in Critically Ill and Non-critically Ill COVID-19 Patients: A Multicenter, Retrospective, Observational Study

Saiping Jiang, Rongrong Wang, Lu Li, Dongsheng Hong, Renping Ru, Yuefeng Rao, Jing Miao, Na Chen, Xiuhua Wu, Ziqi Ye, Yunzhen Hu, Minghua Xie, Minjuan Zuo, Xiaoyang Lu, Yunqing Qiu, Tingbo Liang, Saiping Jiang, Rongrong Wang, Lu Li, Dongsheng Hong, Renping Ru, Yuefeng Rao, Jing Miao, Na Chen, Xiuhua Wu, Ziqi Ye, Yunzhen Hu, Minghua Xie, Minjuan Zuo, Xiaoyang Lu, Yunqing Qiu, Tingbo Liang

Abstract

Background: Liver injury commonly occurs in patients with COVID-19. There is limited data describing the course of liver injury occurrence in patients with different disease severity, and the causes and risk factors are unknown. We aim to investigate the incidence, characteristics, risk factors, and clinical outcomes of liver injury in patients with COVID-19. Methods: This retrospective observational study was conducted in three hospitals (Zhejiang, China). From January 19, 2020 to February 20, 2020, patients confirmed with COVID-19 (≥18 years) and without liver injury were enrolled and divided into non-critically ill and critically ill groups. The incidence and characteristics of liver injury were compared between the two groups. Demographics, clinical characteristics, treatments, and treatment outcomes between patients with or without liver injury were compared within each group. The multivariable logistic regression model was used to explore the risk factors for liver injury. Results: The mean age of 131 enrolled patients was 51.2 years (standard deviation [SD]: 16.1 years), and 70 (53.4%) patients were male. A total of 76 patients developed liver injury (mild, 40.5%; moderate, 15.3%; severe, 2.3%) with a median occurrence time of 10.0 days. Critically ill patients had higher and earlier occurrence (81.5 vs. 51.9%, 12.0 vs. 5.0 days; p < 0.001), greater injury severity (p < 0.001), and slower recovery (50.0 vs. 61.1%) of liver function than non-critically ill patients. Multivariable regression showed that the number of concomitant medications (odds ratio [OR]: 1.12, 95% confidence interval [CI]: 1.05-1.21) and the combination treatment of lopinavir/ritonavir and arbidol (OR: 3.58, 95% CI: 1.44-9.52) were risk factors for liver injury in non-critically ill patients. The metabolism of arbidol can be significantly inhibited by lopinavir/ritonavir in vitro (p < 0.005), which may be the underlying cause of drug-related liver injury. Liver injury was related to increased length of hospital stay (mean difference [MD]: 3.2, 95% CI: 1.3-5.2) and viral shedding duration (MD: 3.0, 95% CI: 1.0-4.9). Conclusions: Critically ill patients with COVID-19 suffered earlier occurrence, greater injury severity, and slower recovery from liver injury than non-critically ill patients. Drug factors were related to liver injury in non-critically ill patients. Liver injury was related to prolonged hospital stay and viral shedding duration in patients with COVID-19. Clinical Trial Registration: World Health Organization International Clinical Trials Registry Platform, ChiCTR2000030593. Registered March 8, 2020.

Keywords: COVID-19; Incidence; disease severity; liver injury; risk factors.

Copyright © 2020 Jiang, Wang, Li, Hong, Ru, Rao, Miao, Chen, Wu, Ye, Hu, Xie, Zuo, Lu, Qiu and Liang.

Figures

Figure 1
Figure 1
Study flowchart.
Figure 2
Figure 2
Kaplan–Meier survival curve for liver injury. (A) Kaplan–Meier curve for liver injury in all enrolled patients. Shaded area shows point-wise SD. (B) Kaplan–Meier survival curves for liver injury in non-critically ill and critically ill patients.
Figure 3
Figure 3
The metabolic interaction between lopinavir/ritonavir and arbidol in vitro. (A) The metabolic inhibition of lopinavir/ritonavir on arbidol in vitro. (B) The metabolic inhibition of arbidol on lopinavir/ritonavir in vitro. LPV/r: lopinavir/ritonavir. **p < 0.01, ***p < 0.001.

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