Systematic Reviews
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World J Virol. Jan 25, 2023; 12(1): 53-67
Published online Jan 25, 2023. doi: 10.5501/wjv.v12.i1.53
COVID-19-related liver injury: Focus on genetic and drug-induced perspectives
Deepak Parchwani, Amit D Sonagra, Sagar Dholariya, Anita Motiani, Ragini Singh
Deepak Parchwani, Amit D Sonagra, Sagar Dholariya, Anita Motiani, Ragini Singh, Department of Biochemistry, All India Institute of Medical Sciences, Rajkot 360001, India
Author contributions: Sonagra AD, Dholariya S and Motiani A contributed to the search and examination of articles, analysis, manuscript writing and proof reading; Parchwani D designed the research study, examined articles and wrote the manuscript; Singh R contributed to literature search and analysis; and all authors have read and approved the final manuscript.
Conflict-of-interest statement: All authors report no relevant conflicts of interest for this article.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2020 Checklist, and the manuscript was prepared and revised according to the PRISMA 2020 guidelines.
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 Non Commercial (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: Sagar Dholariya, MD, Assistant Professor, Department of Biochemistry, All India Institute of Medical Sciences, Jamnagar Road, Khandheri, Rajkot 360001, India. drsagar.dholariya@gmail.com
Received: September 13, 2022
Peer-review started: September 13, 2022
First decision: October 3, 2022
Revised: October 15, 2022
Accepted: December 1, 2022
Article in press: December 1, 2022
Published online: January 25, 2023
Processing time: 126 Days and 16.1 Hours
ARTICLE HIGHLIGHTS
Research background

Available data advocate that the spectrum of hepatic damage in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may be accredited to the direct cytopathic effect of the virus, indirect involvement by systemic immune-mediated inflammation and by iatrogenic causes, i.e., drug induced. Empirical use of potentially hepatotoxic drugs in the management of SARS-CoV-2 infection is considered as one of the major etiopathogenetic factor for liver injury. Moreover, experimental and clinical evidence has shown that an underlying genetic factor may also be present. Hence, it is important to understand the genetics and iatrogenic-based mechanisms for liver dysfunction to make timely remedial measures.

Research motivation

To identify drug-induced liver injury in coronavirus disease 2019 (COVID-19) patients along with a genetic insight for the development of SARS-CoV-2 infection related liver injury to provide better care and timely management of critical patients.

Research objectives

To explore drug-induced and genetic perspectives in the development of SARS-CoV-2 infection related liver injury.

Research methods

A systematic literature search was carried out in multiple electronic databases: PubMed, Reference Citation Analysis, China National Knowledge Infrastructure and Goggle Scholar. The literature was screened using related MeSH keywords and relevant data. The inclusion criteria were English language articles published between December 1, 2020 and April 30, 2022. Reference lists from the articles in the initial search were screened to identify additional literature. There was no exclusion based on the study outcome and stage or severity of SARS-CoV-2 infection. However, studies with animal or cellular models were not included. Other criteria for exclusion were: injury due to SARS-CoV-2 infection itself; and hepatic injury from herbal or dietary supplements.

Research results

The primary analysis of this review revealed that DILI was due to the large-scale use of drugs/off-label drugs in the prophylactic and therapeutic regimen of COVID-19, and the genetic susceptibility underlying liver damage in COVID-19 patients is not yet fully understood. COVID-19-related liver injury (drug-induced and/or genetic-based) predominantly follows the idiosyncratic mechanism, i.e., it is unpredictable with a variable latency period. In most commonly used drugs, the hepatic specific aminotransferases and other biochemical indices were elevated and were significantly associated with severity, hospital stay, number of COVID-19 treatment drugs and worse clinical outcomes.

Research conclusions

Hepatic dysfunction in SARS-CoV-2 infection could be the result of individual drugs or due to drug-drug interactions and may include a subset of the patient population with a genetic propensity. Thus, serial estimation of hepatic indices in SARS-CoV-2 infection hospitalized patients should be performed to make timely corrective actions for iatrogenic causes to avoid clinical deterioration.

Research perspectives

Additional prospective studies are warranted in this regard to justify drug-induced liver injury due to COVID-19 treatment along with the genetic predisposition, which should provide optimization of disease status.