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World J Hepatol. Mar 27, 2023; 15(3): 353-363
Published online Mar 27, 2023. doi: 10.4254/wjh.v15.i3.353
COVID-19 and liver dysfunction in children: Current views and new hypotheses
Yang-Fang Yun, Zhi-Yuan Feng, Jing-Jing Zhang
Yang-Fang Yun, Zhi-Yuan Feng, Jing-Jing Zhang, State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Chemistry and Biomedicine Innovation Center, Nanjing University, Nanjing 210023, Jiangsu Province, China
Author contributions: Yun YF and Zhang JJ conceived of the contents of the manuscript; Yun YF wrote the manuscript and prepared the figures and tables; Zhang JJ and Feng ZY revised the manuscript; all the authors read and approved the final manuscript.
Supported by the National Natural Science Foundation of China, No. 22004063; the Natural Science Foundation of Jiangsu Province, No. 20200303; Program for Innovative Talents and Entrepreneur in Jiangsu, No. 021413006001; the Fundamental Research Funds for the Central Universities, No. 021414380504; and State Key Laboratory of Analytical Chemistry for Life Science, No. 5431ZZXM2206.
Conflict-of-interest statement: The authors have no conflict of interest to disclose.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jing-Jing Zhang, Doctor, Professor, State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Chemistry and Biomedicine Innovation Center, Nanjing University, No. 163 Xianlin Avenue, Qixia District, Nanjing 210023, Jiangsu Province, China. jing15209791@nju.edu.cn
Received: October 28, 2022
Peer-review started: October 28, 2022
First decision: January 3, 2023
Revised: January 14, 2023
Accepted: March 17, 2023
Article in press: March 17, 2023
Published online: March 27, 2023
Abstract

Coronavirus disease 2019 (COVID-19) poses an extremely serious global impact on public healthcare for individuals of all ages, including children. Increasing evidence has shown that liver abnormalities are commonly found in children with COVID-19, and age-related features in innate and adaptive response have been demonstrated. However, there are few reports and studies on COVID-19 related liver injury in children, and the data are scattered. So that many contradictions have arose. This situation is not only due to the serious ethical issues in studying pediatric patients with COVID-19, but also because of the short duration and wide coverage of the COVID-19 epidemic, the severity and complexity of clinical cases varied, as did the inclusion criteria for case reporting and patient outcomes. Therefore, we totaled the incidences, characteristics and pathomechanism of liver injury in children since the COVID-19 outbreak. The etiology of COVID-19-related liver injury is divided into three categories: (1) The direct mechanism involves severe acute respiratory syndrome coronavirus 2 binding to angiotensin-converting enzyme 2 in the liver or bile duct to exert direct toxicity; (2) the indirect mechanisms include an inflammatory immune response and hypoxia; and (3) COVID-19-related treatments, such as mechanical ventilation and antiviral drugs, may cause liver injury. In summary, this minireview provides fundamental insights into COVID-19 and liver dysfunction in children.

Keywords: COVID-19, SARS-CoV-2, Children, Liver injury, Inflammatory immune response, Cytokine storm

Core Tip: There are few cases of liver injury in children with coronavirus disease 2019 (COVID-19) and clinical reports are scarce. We collected reports on COVID-19-related liver injury (CRLI) in children over the last two years and divided the etiology of CRLI into three categories: (1) The direct mechanism involves severe acute respiratory syndrome coronavirus 2 binding to angiotensin-converting enzyme 2 in the liver or bile duct to exert direct toxicity; (2) the indirect mechanisms include an inflammatory immune response and hypoxia; and (3) COVID-19-related treatments, such as mechanical ventilation and antiviral drugs, may cause liver injury. We also discuss the current controversies regarding the pathophysiology of CRLI.