Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Dec 27, 2021; 13(12): 2005-2012
Published online Dec 27, 2021. doi: 10.4254/wjh.v13.i12.2005
Liver dysfunction as a cytokine storm manifestation and prognostic factor for severe COVID-19
Gergana Taneva, Dimitar Dimitrov, Tsvetelina Velikova
Gergana Taneva, Dimitar Dimitrov, Department of Gastroenterology, Sveta Sofia Hospital, Sofia 1618, Bulgaria
Tsvetelina Velikova, Department of Clinical Immunology, University Hospital Lozenetz, Sofia 1407, Bulgaria
Tsvetelina Velikova, Medical Faculty, Sofia University St. Kliment Ohridski, Sofia 1407, Bulgaria
Author contributions: Taneva G, Dimitrov D, and Velikova T wrote different parts of the paper; and all authors revised and approved the final version of the manuscript.
Conflict-of-interest statement: None disclosed.
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: Tsvetelina Velikova, MD, PhD, Assistant Professor, Department of Clinical Immunology, University Hospital Lozenetz, Kozyak 1 Str., Sofia 1407, Bulgaria.
Received: April 22, 2021
Peer-review started: April 22, 2021
First decision: June 15, 2021
Revised: July 2, 2021
Accepted: November 18, 2021
Article in press: November 18, 2021
Published online: December 27, 2021

Liver damage in severe acute respiratory coronavirus 2 infection occurs in patients with or without preexisting liver disorders, posing a significant complication and mortality risk. During coronavirus disease 2019 (COVID-19), abnormal liver function is typically observed. However, liver injury may occur because of the treatment as well. Ischemia, cytokine storm, and hypoxia were identified as the three major factors contributing to liver damage during COVID-19. Indeed, raised liver enzymes during hospitalizations may be attributed to medications used, as well as sepsis and shock. As a result, the proportion of hospitalized patients afflicted with COVID-19 and pathological liver biomarkers varies from 14% to 53%. Aminotransferases and bilirubin are found most often elevated. Usually, increased gamma-glutamyltransferase, alkaline phosphatase, and decreased serum albumin levels are demonstrated. Additionally, although there is no specific treatment for COVID-19, many of the drugs used to treat the infection are hepatotoxic. In this mini-review, we focus on how liver dysfunction can be one of the features associated with the COVID-19 cytokine storm. Furthermore, data show that liver injury can be an independent predictor of severe COVID-19, the need for hospitalization, and death.

Keywords: Liver dysfunction, Liver damage, Cytokine storm, Prognostic factor, COVID-19, Severe COVID-19, SARS-CoV-2, Aspartate aminotransferase, Alanine aminotrans-ferase, Bilirubin, Interleukin-6

Core Tip: Looking at the liver tests in patients with severe coronavirus disease 2019 (COVID-19), C-reactive protein (CRP) showed a strong correlation with the aspartate aminotransferase (AST) levels. This was observed in both intensive care units (ICU) and non-ICU patients. However, CRP levels were higher in non-ICU patients with liver damage, whereas alanine aminotransferase (ALT) was higher in ICU COVID-19 patients. Thus, like interleukin-6 (IL-6), ferritin, and CRP correlated directly with AST and ALT levels in non-ICU patients, there is a direct correlation of IL-6 and acute phase proteins with AST in severe COVID-19 cases. These observations confirm the critical impact of systemic inflammation and specifically elevated IL-6 during severe acute respiratory coronavirus 2 cytokine storm on liver injury.