Journal of Clinical and Translational Hepatology

Journal of Clinical and Translational Hepatology

Thursday, 12 / 09 / 2021




COVID-19 and Indirect Liver Injury: A Narrative Synthesis of the Evidence

Francisco Idalsoaga1 , Gustavo Ayares1 , Juan Pablo Arab1,2 and Luis Antonio Díaz1,*

1  Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
2  Centro de Envejecimiento y Regeneración (CARE), Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
*Correspondence to:Luis Antonio Díaz, Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Marcoleta 367, Santiago 8330024, Chile. ORCID: . Tel/Fax:+56-2-2354-3820, E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

Journal of Clinical and Translational Hepatology 2021;9(5):760-768 DOI: 10.14218/JCTH.2020.00140
Received:November 30, 2020 Accepted:May 13, 2021 Published online:June 16, 2021


The liver is frequently affected by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection. The most common manifestations are mildly elevated alanine aminotransferase and aspartate aminotransferase, with a prevalence of 16-53% among patients. Cases with severe coronavirus disease 2019 (COVID-19) seem to have higher rates of acute liver dysfunction, and the presence of abnormal liver tests at admission signifies a higher risk of severe disease during hospitalization. Patients with chronic liver diseases also have a higher risk of severe disease and mortality (mainly seen in patients with metabolic-associated fatty liver disease). Several pathways of damage have been proposed in the liver involvement of COVID-19 patients; although, the end-cause is most likely multifactorial. Abnormal liver tests have been attributed to the expression of angiotensin-converting enzyme 2 receptors in SARS-CoV-2 infection. This enzyme is expressed widely in cholangiocytes and less in hepatocytes. Other factors attributed to liver damage include drug-induced liver injury, uncontrolled release of proinflammatory molecules (“cytokine storm”), pneumonia-associated hypoxia, and direct damage by the infection. Hepatic steatosis, vascular thrombosis, fibrosis, and inflammatory features (including Kupffer cell hyperplasia) are the most common liver histopathological findings in deceased COVID-19 patients, suggesting important indirect mechanisms of liver damage. In this translational medicine-based narrative review, we summarize the current data on the possible indirect mechanisms involved in liver damage due to COVID-19, the histopathological findings, and the impact of these mechanisms in patients with chronic liver disease.


COVID-19, SARS-CoV-2, Liver hepatitis, Liver injury, Novel coronavirus

Journal of Clinical and Translational Hepatology 2021 vol. 9, 760-768  [ Html  ] [ PDF Full-text ]

© 2021 Authors. This is an Open Access article distributed under the terms of the  Creative Commons Attribution-Noncommercial 4.0 License(CC BY-NC 4.0), permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


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