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World J Gastroenterol. Apr 14, 2023; 29(14): 2064-2077
Published online Apr 14, 2023. doi: 10.3748/wjg.v29.i14.2064
Insight into the liver dysfunction in COVID-19 patients: Molecular mechanisms and possible therapeutic strategies
Naina Khullar, Jasvinder Singh Bhatti, Satwinder Singh, Bhawana Thukral, P Hemachandra Reddy, Gurjit Kaur Bhatti
Naina Khullar, Department of Zoology, Mata Gujri College, Fatehgarh Sahib 140407, Punjab, India
Jasvinder Singh Bhatti, Laboratory of Translational Medicine and Nanotherapeutics, Department of Human Genetics and Molecular Medicine, School of Health Sciences, Central University of Punjab, Bathinda 151401, Punjab, India
Satwinder Singh, Department of Computer Science and Technology, Central University of Punjab, Bathinda 151401, Punjab, India
Bhawana Thukral, Department of Nutrition and Dietetics, University Institute of Applied Health Sciences, Chandigarh University, Mohali 140413, Punjab, India
P Hemachandra Reddy, Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, United States
Gurjit Kaur Bhatti, Department of Medical Lab Technology, University Institute of Applied Health Sciences, Chandigarh University, Mohali 140413, Punjab, India
Author contributions: Khullar N and Bhatti JS contributed equally, performed the majority of the writing, and prepared the figures and tables; Singh S and Thukral B performed data accusation and writing; Reddy PH provided input on writing the paper; Bhatti GK designed the outline and coordinated the writing of the paper; and all authors have read and approved the final manuscript.
Supported by the Science and Engineering Research Board India grant, No. TAR/2020/000430 and EEQ/2020/000188; and Indian Council of Medical Research grant, No. BMI/12(08)/2021-6329.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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:
Corresponding author: Gurjit Kaur Bhatti, BSc, MSc, PhD, Associate Professor, Department of Medical Lab Technology, University Institute of Applied Health Sciences, Chandigarh University, Gharuan, Mohali 140413, Punjab, India.
Received: September 28, 2022
Peer-review started: September 28, 2022
First decision: October 17, 2022
Revised: October 23, 2022
Accepted: March 21, 2023
Article in press: March 21, 2023
Published online: April 14, 2023

As of June 2022, more than 530 million people worldwide have become ill with coronavirus disease 2019 (COVID-19). Although COVID-19 is most commonly associated with respiratory distress (severe acute respiratory syndrome), meta-analysis have indicated that liver dysfunction also occurs in patients with severe symptoms. Current studies revealed distinctive patterning in the receptors on the hepatic cells that helps in viral invasion through the expression of angiotensin-converting enzyme receptors. It has also been reported that in some patients with COVID-19, therapeutic strategies, including repurposed drugs (mitifovir, lopinavir/ritonavir, tocilizumab, etc.) triggered liver injury and cholestatic toxicity. Several proven indicators support cytokine storm-induced hepatic damage. Because there are 1.5 billion patients with chronic liver disease worldwide, it becomes imperative to critically evaluate the molecular mechanisms concerning hepatotropism of COVID-19 and identify new potential therapeutics. This review also designated a comprehensive outlook of comorbidities and the impact of lifestyle and genetics in managing patients with COVID-19.

Keywords: COVID-19, Liver damage, Pharmacotherapy, Cytokine storm, Molecular mechanisms

Core Tip: Several review articles have contributed to the pathophysiology, therapeutic strategies, vaccine development, and clinical trials of coronavirus disease 2019 (COVID-19). Since the liver is the primary site of immune protein synthesis, any liver defect may compromise the immune system. Patients with chronic liver disease are at a higher risk of severe COVID-19. This review article demonstrated the pathophysiology and molecular mechanisms responsible for more severe outcomes in patients with hepatic defects. Further, we critically evaluated the molecular mechanisms concerning hepatotropism in patients with COVID-19, which could lead to the development of new therapeutics.