Rodriguez-Espada A, Salgado-de la Mora M, Rodriguez-Paniagua BM, Limon-de la Rosa N, Martinez-Gutierrez MI, Pastrana-Brandes S, Navarro-Alvarez N. Histopathological impact of SARS-CoV-2 on the liver: Cellular damage and long-term complications. World J Gastroenterol 2024; 30(22): 2866-2880 [PMID: 38947288 DOI: 10.3748/wjg.v30.i22.2866]
Corresponding Author of This Article
Nalu Navarro-Alvarez, MD, PhD, Assistant Professor, Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, 15 Vasco de Quiroga, Mexico 14080, Mexico. nalu.navarroa@incmnsz.mx
Research Domain of This Article
Infectious Diseases
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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/
World J Gastroenterol. Jun 14, 2024; 30(22): 2866-2880 Published online Jun 14, 2024. doi: 10.3748/wjg.v30.i22.2866
Histopathological impact of SARS-CoV-2 on the liver: Cellular damage and long-term complications
Alfonso Rodriguez-Espada, Moises Salgado-de la Mora, Briana Mariette Rodriguez-Paniagua, Nathaly Limon-de la Rosa, Monica Itzel Martinez-Gutierrez, Santiago Pastrana-Brandes, Nalu Navarro-Alvarez
Alfonso Rodriguez-Espada, Briana Mariette Rodriguez-Paniagua, Santiago Pastrana-Brandes, Nalu Navarro-Alvarez, Department of Molecular Biology, Universidad Panamericana School of Medicine, Campus México, Mexico 03920, Mexico
Moises Salgado-de la Mora, Department of Internal Medicine, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico 14080, Mexico
Nathaly Limon-de la Rosa, Nalu Navarro-Alvarez, Department of Surgery, University of Colorado Anschutz Medical Campus, Denver, CO 80045, United States
Monica Itzel Martinez-Gutierrez, PECEM, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico 04360, Mexico
Nalu Navarro-Alvarez, Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico 14080, Mexico
Author contributions: Rodriguez-Espada A, Salgado-de La Mora M, Mariette Rodriguez-Paniagua B, Limon-de la Rosa N, Itzel Martinez-Gutierrez M, Pastrana-Brandes S, bibliography search, draft writing and preparation of figures and tables; Navarro-Alvarez N, conceived, wrote and critically revised the work.
Conflict-of-interest statement: We have no financial relationships to disclose.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Nalu Navarro-Alvarez, MD, PhD, Assistant Professor, Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, 15 Vasco de Quiroga, Mexico 14080, Mexico. nalu.navarroa@incmnsz.mx
Received: March 8, 2024 Revised: May 8, 2024 Accepted: May 24, 2024 Published online: June 14, 2024 Processing time: 89 Days and 6.8 Hours
Abstract
Coronavirus disease 2019 (COVID-19), caused by the highly pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily impacts the respiratory tract and can lead to severe outcomes such as acute respiratory distress syndrome, multiple organ failure, and death. Despite extensive studies on the pathogenicity of SARS-CoV-2, its impact on the hepatobiliary system remains unclear. While liver injury is commonly indicated by reduced albumin and elevated bilirubin and transaminase levels, the exact source of this damage is not fully understood. Proposed mechanisms for injury include direct cytotoxicity, collateral damage from inflammation, drug-induced liver injury, and ischemia/hypoxia. However, evidence often relies on blood tests with liver enzyme abnormalities. In this comprehensive review, we focused solely on the different histopathological manifestations of liver injury in COVID-19 patients, drawing from liver biopsies, complete autopsies, and in vitro liver analyses. We present evidence of the direct impact of SARS-CoV-2 on the liver, substantiated by in vitro observations of viral entry mechanisms and the actual presence of viral particles in liver samples resulting in a variety of cellular changes, including mitochondrial swelling, endoplasmic reticulum dilatation, and hepatocyte apoptosis. Additionally, we describe the diverse liver pathology observed during COVID-19 infection, encompassing necrosis, steatosis, cholestasis, and lobular inflammation. We also discuss the emergence of long-term complications, notably COVID-19-related secondary sclerosing cholangitis. Recognizing the histopathological liver changes occurring during COVID-19 infection is pivotal for improving patient recovery and guiding decision-making.
Core Tip: Severe acute respiratory syndrome coronavirus 2 infection is linked to significant liver injury, emerging from the facilitated entry of the virus into liver cells, including cholangiocytes and endothelial cells, due to increased receptor expression. This invasion triggers critical cellular alterations such as mitochondrial swelling, endoplasmic reticulum dilation, and hepatocyte apoptosis. Confirmed by biopsy or autopsy, the presence of viral particles in liver tissues correlates with extensive histological damage, characterized by necrosis, steatosis, cholestasis, and inflammation. Such findings highlight the acute hepatic impact of coronavirus disease 2019 (COVID-19) and signal the risk of severe long-term complications, such as COVID-19-associated sclerosing cholangitis, emphasizing the profound and enduring effect of the virus on liver health.
