Systematic Reviews
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Meta-Anal. Apr 28, 2021; 9(2): 193-207
Published online Apr 28, 2021. doi: 10.13105/wjma.v9.i2.193
Laboratory hematologic features of COVID-19 associated liver injury: A systematic review
John L Frater, Tianjiao Wang, Yi-Shan Lee
John L Frater, Tianjiao Wang, Yi-Shan Lee, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, United States
Author contributions: Frater JL designed the research study, performed the research, analyzed the data, and wrote the manuscript; Wang T and Lee YS analyzed the data; All authors have read and approved the final manuscript.
Conflict-of-interest statement: All authors declare no conflicts-of-interest related to this article.
PRISMA 2009 Checklist statement: The manuscript was prepared and revised according to the PRISMA 2009 Checklist.
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: John L Frater, MD, Associate Professor, Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid Ave, Campus Box 8118, 3rd Floor, Rm 3421, Institute of Health Bldg, St. Louis, MO 63110, United States.
Received: January 28, 2021
Peer-review started: January 28, 2021
First decision: February 24, 2021
Revised: March 31, 2021
Accepted: April 23, 2021
Article in press: April 23, 2021
Published online: April 28, 2021
Research background

Hematology laboratory testing has an established role in risk stratification in patients with coronavirus disease 2019 (COVID-19) disease. Liver injury is common in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The utility of hematology laboratory data in diagnosis and risk stratification of patients with COVID-19-related liver injury is unclear.

Research motivation

To what degree are the abnormalities in hematologic parameters seen in the general population of patients with COVID-19 also seen in the subpopulation of patients with associated liver injury? Is liver injury in COVID-19 indicative of severe disease. Does liver injury correlate with hematologic markers of severe disease? What is the quality of literature that addresses these questions?

Research objectives

The objectives of this study were: To determine the extent to which previously reported hematologic abnormalities are seen in patients with COVID-19-associated liver injury; to assess whether liver injury in COVID-19 is a sign of severe disease, and the extent to which liver injury correlates with markers of severe disease; and based on the extant literature, to determine the quality of this evidence.

Research methods

This study was conducted as a Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant systematic review. We extracted information from cohort studies related to the topic of liver injury in COVID-19 in which laboratory hematology data were included.

Research results

In all, 32 articles were included in the systematic review, which consisted of 22 articles with a cohort of COVID-19 patients with liver injury; 5 comparing non-severe vs severe COVID-19 populations in which liver injury was addressed and 5 other cohort studies with a focus on liver injury. White blood cell count, absolute neutrophil count, absolute lymphocyte count (ALC), and hemoglobin were the parameters most useful to distinguish COVID-19 with liver injury from COVID-19 without liver injury. ALC and d-dimer were potentially useful in distinguishing non-severe from severe COVID-19. Liver injury was more frequently seen in cohorts with severe disease. Most studies were of high quality (24/48, 86%) with 4/28 (14%) of moderate quality and 0 of low quality.

Research conclusions

The use of select hematologic parameters in diagnosis and risk stratification of liver injury in COVID-19 patients appears warranted. The relevant literature is high quality, but is limited by the small number of studies with high statistical power and the variable definition of COVID-19 liver injury in the literature.

Research perspectives

Future studies, preferably with a prospective design, large numbers of patients, and rigorous definition of liver injury would be useful to validate these findings.