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

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 medicinebased 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.

Vaccination against COVID‐19 decreases hospitalizations in patients with cirrhosis: Results from a nationwide analysis

“…Also, SARS‐CoV‐2 infection by itself can elevate the liver chemistries and affect liver function. 5 This evidence highlights the need to protect these populations from exposure to SARS‐CoV‐2 infection. 6 …”

“…This effect increases according to the severity of cirrhosis and contributes to acute hepatic decompensation in 46% of patients. Also, SARS‐CoV‐2 infection by itself can elevate the liver chemistries and affect liver function 5 . This evidence highlights the need to protect these populations from exposure to SARS‐CoV‐2 infection 6 …”

Liver, NAFLD and COVID-19

“…a) Systemic Inflammatory Response Syndrome (SIRS) is characterized by an excessive uncontrolled secretion of proinflammatory cytokines (interleukins, interferons, TNFs, chemokines) that induce differentiation of B cells and T cells expansion/activation [49]. Such a reaction, commonly described as "cytokine storm" is often observed in severe COVID-19 and can lead to multiple organ failure, including severe liver damage [49]. Additionally, it may facilitate cholestasis by repressing hepatobiliary excretory function and by promoting ductular proliferation [24].…”

“…Acute respiratory distress syndrome (ARDS) is one of the most common severe complications by SARS-CoV-2 and demands intensive treatment with high positive end-expiratory pressures (PEEPs) combined often with vasoconstrictory treatment. Low systemic arterial pressure inevitably leads to low hepatic arterial perfusion, which results in hepatocellular hypoxia [49,55]. Hepatocellular hypoxia promotes lipid accumulation, mitochondrial damage and production of reactive oxygen species, thus further inducing inflammation and finally leading to necrosis.…”

SARS-CoV-2-fehérjék kimutatása immunhisztokémiai módszerrel emberi szövetekben.

“…Nem világos azonban, hogy az extrapulmonalis elváltozásokért a vírus közvetlen sejtkárosító hatása felelős-e, vagy annak közvetett hatása, így a vírus kiváltotta "citokinvihar", a szív-és érrendszeri komplikációk, a hypoxia, a beteg gyógyszeres kezelésének hatása stb. [4,10,[19][20][21]. Ennek eldöntésében segíthet a SARS-CoV-2 egyes komponenseinek, így tüske-és nukleokapszid-fehérjéinek, valamint a vírus-ribonukleinsavnak (RNS) az in situ kimutatása a sejtekben és a szövetekben.…”