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©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
High prevalence of hepatic steatosis and vascular thrombosis in COVID-19: A systematic review and meta-analysis of autopsy data
Luis Antonio Díaz, Francisco Idalsoaga, Macarena Cannistra, Roberto Candia, Daniel Cabrera, Francisco Barrera, Alejandro Soza, Rondell Graham, Arnoldo Riquelme, Marco Arrese, Michael D Leise, Juan Pablo Arab
Luis Antonio Díaz, Roberto Candia, Francisco Barrera, Alejandro Soza, Arnoldo Riquelme, Juan Pablo Arab, Department of Gastroenterology, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago 8320000, Chile
Francisco Idalsoaga, Department of Internal Medicine, Pontificia Universidad Católica de Chile, Santiago 8320000, Chile
Macarena Cannistra, School of Medicine, Pontificia Universidad Católica de Chile, Santiago 8320000, Chile
Daniel Cabrera, Facultad de Ciencias Médicas, Universidad Bernardo O'Higgins, Santiago 8320000, Chile
Rondell Graham, Department of Laboratory Medicine and Pathology, Mayo Clinic Rochester, Minnesota, MN 55902, United States
Marco Arrese, Department of Gastroenterology, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago 8320000, Chile
Michael D Leise, Division of Gastroenterology and Hepatology, Mayo Clinic Rochester, Minnesota, MN 55905, United States
Author contributions: Díaz LA and Arab JP are responsible for the overall content of the project and the manuscript submitted as guarantors of the project; Díaz LA, Idalsoaga F and Cannistra M had full access to all the data in the study; Díaz LA, Idalsoaga F, Candia R and Arab JP take responsibility for the integrity of the data and the accuracy of the data analysis; Díaz LA and Arab JP take the final decision to submit for publication; Díaz LA, Idalsoaga F, Cannistra M, Candia R, Arab JP, Graham R, Leise MD and Riquelme A contributed analysis or interpretation of data; Díaz LA, Arab JP, Leise MD, Graham R and Riquelme A contributed drafting of the manuscript; Díaz LA, Idalsoaga F, Cannistra M, Candia R, Cabrera D, Barrera F, Soza A, Graham R, Riquelme A, Arrese M, Leise MD and Arab JP contributed critical revision of the manuscript for relevant intellectual content; Díaz LA and Candia R contributed statistical analysis.
Supported by Chilean Government Through the Fondo Nacional de Desarrollo Científico y Tecnológico, No. 1200227, No. 1191183 and No. 1191145; Comisión Nacional de Investigación Científica y Tecnológica (CONICYT, CARE Chile UC), No. AFB170005; and European Union’s Horizon 2020 Research, No. 825510.
Conflict-of-interest statement: The authors have nothing to disclose.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and 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:
http://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Juan Pablo Arab, MD, Assistant Professor, Department of Gastroenterology, Pontificia Universidad Católica de Chile, Diagonal Paraguay 362, Departamento de Gastroenterología, Santiago 8320000, Chile. jparab@med.puc.cl
Received: October 21, 2020
Peer-review started: October 21, 2020
First decision: November 13, 2020
Revised: November 26, 2020
Accepted: December 6, 2020
Article in press: December 6, 2020
Published online: December 28, 2020
BACKGROUND
Coronavirus disease 2019 (COVID-19) disease can frequently affect the liver. Data on hepatic histopathological findings in COVID-19 is scarce.
AIM
To characterize hepatic pathological findings in patients with COVID-19.
METHODS
We conducted a systematic review with meta-analysis registered on PROSPERO (CRD42020192813), following PRISMA guidelines. Eligible trials were those including patients of any age and COVID-19 diagnosis based on a molecular test. Histopathological reports from deceased COVID-19 patients undergoing autopsy or liver biopsy were reviewed. Articles including less than ten patients were excluded. Proportions were pooled using random-effects models. Q statistic and I2 were used to assess heterogeneity and levels of evidence, respectively.
RESULTS
We identified 18 studies from 7 countries; all were case reports and case series from autopsies. All the patients were over 15 years old, and 67.2% were male. We performed a meta-analysis of 5 studies, including 116 patients. Pooled prevalence estimates of liver histopathological findings were hepatic steatosis 55.1% [95% confidence interval (CI): 46.2-63.8], congestion of hepatic sinuses 34.7% (95%CI: 7.9-68.4), vascular thrombosis 29.4% (95%CI: 0.4-87.2), fibrosis 20.5% (95%CI: 0.6-57.9), Kupffer cell hyperplasia 13.5% (95%CI: 0.6-54.3), portal inflammation 13.2% (95%CI: 0.1-48.8), and lobular inflammation 11.6% (95%CI: 0.3-35.7). We also identified the presence of venous outflow obstruction, phlebosclerosis of the portal vein, herniated portal vein, periportal abnormal vessels, hemophagocytosis, and necrosis.
CONCLUSION
We found a high prevalence of hepatic steatosis and vascular thrombosis as major histological liver features. Other frequent findings included portal and lobular inflammation and Kupffer cell hyperplasia or proliferation. Further studies are needed to establish the mechanisms and implications of these findings.
Core Tip: In this systematic review of 18 studies, we identified that hepatic steatosis, congestion of hepatic sinuses, and vascular thrombosis are the main histological findings in deceased coronavirus disease 2019 (COVID-19) patients. Fibrosis is a common histological finding in deceased COVID-19 patients. Kupffer cell hyperplasia, portal inflammation, and lobular inflammation are related to the severe acute respiratory syndrome coronavirus 2 inflammatory process and are frequent histological findings. Other vascular abnormalities (such as venous outflow obstruction, phlebosclerosis of the portal vein, herniated portal vein, periportal abnormal vessels) are frequent histological finding in deceased COVID-19 patients.
