Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Oct 28;9(5):760-768.
doi: 10.14218/JCTH.2020.00140. Epub 2021 Jun 16.

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

Francisco Idalsoaga  1 , Gustavo Ayares  1 , Juan Pablo Arab  1   2 , Luis Antonio Díaz  1
Affiliations
Review

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

Francisco Idalsoaga et al. J Clin Transl Hepatol. .

Abstract

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.

Keywords: COVID-19; Liver hepatitis; Liver injury; Novel coronavirus; SARS-CoV-2.

PubMed Disclaimer

Conflict of interest statement

The authors have no conflict of interests related to this publication.

Figures

Fig. 1
Fig. 1. Mechanisms involved in the pathogenesis of liver damage in patients with COVID-19 infection.
The pathogenic process in COVID-19 begins when the virus binding to ACE2 in the target cell via receptor in the viral capsule. Some patients develop SIRS characterized by a “cytokine storm”. The activated T cells produced GM-CSF, IL-6, and other proinflammatory factors. The inflammatory monocytes CD14+CD16+ respond to GM-CSF, producing a larger amount of IL-6 and other proinflammatory factors. Other factors such as hepatic ischemia, hypoxia-reperfusion dysfunction, and DILI probably perpetuate and induce more significant damage. Other mechanisms of damage, including intestinal abnormalities, have been raised (abnormal permeability, dysbiosis, viral translocation); however, without clear evidence yet. ACE2, angiotensin-converting enzyme 2; COVID-19, coronavirus disease 2019; DILI, drug-induced liver injury; GM-CSF, granulocyte-macrophage colony-stimulating factor; IL, interleukin.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;382(8):727–733. doi: 10.1056/NEJMoa2001017. - DOI - PMC - PubMed
    1. Cucinotta D, Vanelli M. WHO declares COVID-19 a pandemic. Acta Biomed. 2020;91(1):157–160. doi: 10.23750/abm.v91i1.9397. - DOI - PMC - PubMed
    1. Verelst F, Kuylen E, Beutels P. Indications for healthcare surge capacity in European countries facing an exponential increase in coronavirus disease (COVID-19) cases, March 2020. Euro Surveill. 2020;25(13):2000323. doi: 10.2807/1560-7917.ES.2020.25.13.2000323. - DOI - PMC - PubMed
    1. Mannelli C. Whose life to save? Scarce resources allocation in the COVID-19 outbreak. J Med Ethics. 2020;46(6):364–366. doi: 10.1136/medethics-2020-106227. - DOI - PubMed
    1. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382(18):1708–1720. doi: 10.1056/NEJMoa2002032. - DOI - PMC - PubMed