Covid‐19 and Liver Injury: Role of Inflammatory Endotheliopathy, Platelet Dysfunction, and Thrombosis

McConnell, Matthew; Kondo, Reiichiro; Kawaguchi, Nao; Iwakiri, Yasuko

doi:10.1002/hep4.1843

Cited by 57 publications

(48 citation statements)

References 156 publications

(194 reference statements)

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“…Acute dysregulations in hemostasis and inflammation are prominent features of patients with moderate-to-severe COVID-19 (3). Thrombi have been detected in the lung, heart, brain, and liver of COVID-19 patients, and the prevalence of deep vein thrombosis in hospitalized patients with an infection is significantly increased (4)(5)(6). Microthrombosis, also extensively documented by autopsy reports, reflects the increased platelet activation and subsequent fibrin clot formation in the pulmonary microvasculature in 80%-100% of lungs examined (7).…”

Section: Introductionmentioning

confidence: 99%

Disease Severity in Moderate-to-Severe COVID-19 Is Associated With Platelet Hyperreactivity and Innate Immune Activation

et al. 2022

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BackgroundHemostasis and inflammation are both dysregulated in patients with moderate-to-severe coronavirus disease 2019 (COVID-19). Yet, both processes can also be disturbed in patients with other respiratory diseases, and the interactions between coagulation, inflammation, and disease severity specific to COVID-19 are still vague.MethodsHospitalized patients with acute respiratory symptoms and with severe acute respiratory syndrome coronavirus 2 (SARS-CoV2)-positive (COVpos) and SARS-CoV2-negative (COVneg) status were included. We assessed adenosine diphosphate (ADP)-, thrombin receptor activator peptide 6 (TRAP)-, and arachidonic acid (AA)-induced platelet reactivity by impedance aggregometry, as well as leukocyte subtype spectrum and platelet-leukocyte aggregates by flow cytometry and inflammatory cytokines by cytometric bead array.ResultsADP-, TRAP-, and AA-induced platelet reactivity was significantly higher in COVpos than in COVneg patients. Disease severity, assessed by sequential organ failure assessment (SOFA) score, was higher in COVpos than in COVneg patients and again higher in deceased COVpos patients than in surviving COVpos. The SOFA score correlated significantly with the mean platelet volume and TRAP-induced platelet aggregability. A larger percentage of classical and intermediate monocytes, and of CD4pos T cells (TH) aggregated with platelets in COVpos than in COVneg patients. Interleukin (IL)-1 receptor antagonist (RA) and IL-6 levels were higher in COVpos than in COVneg patients and again higher in deceased COVpos patients than in surviving COVpos. IL-1RA and IL-6 levels correlated with the SOFA score in COVpos but not in COVneg patients. In both respiratory disease groups, absolute levels of B-cell-platelet aggregates and NK-cell-platelet aggregates were correlated with ex vivo platelet aggegation upon stimulation with AA and ADP, respectively, indicating a universal, but not a COVID-19-specific mechanism.ConclusionIn moderate-to-severe COVID-19, but not in other respiratory diseases, disease severity was associated with platelet hyperreactivity and a typical inflammatory signature. In addition to a severe inflammatory response, platelet hyperreactivity associated to a worse clinical outcome in patients with COVID-19, pointing to the importance of antithrombotic therapy for reducing disease severity.

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Section: Introductionmentioning

confidence: 99%

Disease Severity in Moderate-to-Severe COVID-19 Is Associated With Platelet Hyperreactivity and Innate Immune Activation

et al. 2022

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“…[1][2][3] It has been reported that infection with coronavirus disease 2019 induces severe ALI and lacks effective treatment. [4] According to the World Health Organization, the incidence of ALI continues to increase due to drug abuse, the heavy use of pesticides, environmental pollution, and unhealthy lifestyle habits. [1][2][3] There are three potential outcomes to ALI: disease resolution, progression to chronic liver injury, and progression to acute liver failure.…”

Section: Introductionmentioning

confidence: 99%

Scavenging ROS to Alleviate Acute Liver Injury by ZnO‐NiO@COOH

Liu

Zhu

et al. 2022

Advanced Science

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Currently, the incidence of acute liver injury (ALI) is increasing year by year, and infection with coronavirus disease 2019 (COVID-19) can also induce ALI, but there are still no targeted therapeutic drugs. ZnO-NiO particles is mainly used to clean up reactive oxygen species (ROS) in industrial wastewater, and it is insoluble in water. Its excellent properties are discovered and improved by adding shuttle-based bonds to make it more water-soluble. ZnO-NiO@COOH particles are synthetically applied to treat ALI. The p-n junction in ZnO-NiO@COOH increases the surface area and active sites, thereby creating large numbers of oxygen vacancies, which can quickly adsorb ROS. The content in tissues and serum levels of L-glutathione (GSH) and the GSH/oxidized GSH ratio are measured to assess the capacity of ZnO-NiO@COOH particles to absorb ROS. The ZnO-NiO@COOH particles significantly reduce the expression levels of inflammatory factors (i.e., IL-1, IL-6, and TNF-𝜶), macrophage infiltration, and granulocyte activation. ZnO-NiO@COOH rapidly adsorb ROS in a short period of time to block the generation of inflammatory storms and gain time for the follow-up treatment of ALI, which has important clinical significance.

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“…Additionally, it may facilitate cholestasis by repressing hepatobiliary excretory function and by promoting ductular proliferation 24 . A recent study demonstrated that IL-6 is probably the main cytokine orchestrating this inflammatory response leading to liver damage 50 . Specifically, high levels of interleukin-6 lead through IL-6 signaling to increased expression of procoagulants, proinflammatory factors [von Willebrand factor (vWF) and factor VIII], increased cell surface vWF and enhanced platelet attachment in liver sinusoidal endothelial cells, thus linking IL-6-mediated procoagulant endotheliopathy-endothelial inflammation with vascular inflammation and coagulation commonly observed in COVID-19 50 .…”

Section: Introductionmentioning

confidence: 99%

Liver, NAFLD and COVID-19

Hoffmann¹,

Gerber²,

Cavelti-Weder³

et al. 2022

Horm Metab Res

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Coronavirus disease 2019 (COVID-19) is characterized by a wide clinical spectrum that includes abnormalities in liver function indicative of liver damage. Conversely, people with liver diseases are at higher risk of severe COVID-19. In the current review, we summarize first the epidemiologic evidence describing the bidirectional relationship between COVID-19 and liver function/liver diseases. Additionally, we present the most frequent histologic findings as well as the most important direct and indirect mechanisms supporting a COVID-19 mediated liver injury. Furthermore, we focus on the most frequent liver disease in the general population, non-alcoholic or metabolic-associated fatty liver disease (NAFLD/MAFLD), and describe how COVID-19 may affect NAFLD/MAFLD development and progression and conversely how NAFLD/MAFLD may further aggravate a COVID-19 infection. Finally, we present the long-term consequences of the pandemic on the development and management of NAFLD.

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Covid‐19 and Liver Injury: Role of Inflammatory Endotheliopathy, Platelet Dysfunction, and Thrombosis

Cited by 57 publications

References 156 publications

Disease Severity in Moderate-to-Severe COVID-19 Is Associated With Platelet Hyperreactivity and Innate Immune Activation

Disease Severity in Moderate-to-Severe COVID-19 Is Associated With Platelet Hyperreactivity and Innate Immune Activation

Scavenging ROS to Alleviate Acute Liver Injury by ZnO‐NiO@COOH

Liver, NAFLD and COVID-19

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