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

Liver injury is a common complication of infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The utility of laboratory hematology data in the diagnosis and risk stratification of patients with coronavirus disease 2019 (COVID-19) has not been comprehensively examined.


To address the following. (1) Are the abnormalities in hematologic parameters seen in the general population of patients with COVID-19 also seen in those patients with associated liver injury? (2) Is liver injury in COVID-19 a sign of severe disease and does liver injury correlate with hematologic markers of severe disease? And (3) What is the quality of this evidence?


To address these questions, a comprehensive systematic review was performed. We searched the peer reviewed medical literature using MEDLINE (PubMed interface), Web of Science, and EMBASE for cohort studies that specifically addressed liver injury and COVID-19 without limitation of date of publication or language. A quality assessment of the studies was performed using the Newcastle-Ottawa Scale.


Thirty-two articles were suitable for inclusion in our systematic review. These included 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 helpful in distinguishing COVID-19 with liver injury from COVID-19 without liver injury. ALC and d-dimer were identified as being 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.


Our study supports the use of select hematologic parameters in diagnosis and risk stratification of liver injury in COVID-19 patients. Although of overall high quality, the current medical literature is limited by the small number of studies with high statistical power and the variable definition of COVID-19 liver injury in the literature.

Keywords: COVID-19, SARS-CoV-2, Laboratory hematology, Systematic review, Coagulation, Liver injury

Core Tip: The use of laboratory hematology data as biomarkers of disease has not been examined for coronavirus disease 2019 (COVID-19) patients with liver injury, and the clinical significance of liver injury in COVID-19 is unclear. By means of a systematic review we showed that blood cell count, absolute neutrophil count, absolute lymphocyte count (ALC), and hemoglobin are of potential use in identifying liver failure in COVID-19. ALC and d-dimer have potential utility in distinguishing severe from non-severe disease in patients with liver injury. Our findings provide a rationale for further studies with sufficiently large numbers of patients and rigorous definition of liver injury to validate these findings.