COVID-19, liver dysfunction and pathophysiology: A conceptual discussion

Abstract

The intra and extracellular pathways of hepatic injury by coronavirus disease 2019 (COVID-19) are still being studied. Understanding them is important to treat this viral disease and other liver and biliary tract disorders. Thus, this paper aims to present three hypotheses about liver injury caused by COVID-19: (1) The interactions between severe acute respiratory syndrome coronavirus 2 spike protein and membrane receptors in the hepatocyte; (2) The dysbiosis and “gut-liver axis” disruption in patients with serious clinical presentations of COVID-19; and (3) The inflammatory response exacerbated through the production of interleukins such as interleukin-6. However, despite these new perspectives, the pathophysiological process of liver injury caused by COVID-19 is still complex and multifactorial. Thus, understanding all these variables is a challenge to science but also the key to propose individualized and effective patient therapies.

Meta-analysis of liver injury in patients with COVID-19

“…Studies have found that ACE2 is highly expressed in the liver, especially in the intrahepatic bile duct epithelial cells. [59] Therefore, the liver is also one of the target organs for COVID-19 attack. Deng et al [60] compared the clinical characteristics of liver injury in patients infected with Delta and Omicron variants, and found that the liver injury secondary to the 2 variants was mainly caused by elevated cholangiocyte injury parameters (TBA, γ-glutamyl transferase or ALP), and there was no significant difference in the incidence of liver injury between the 2 types.…”

The impact of COVID-19 on liver injury in various age

“…In the next step, these cytokines stimulate the expression of genes relevant to the immune response, and through intracellular signaling, especially using IL-6, other pro-inflammatory cytokine biomarkers like tumor necrosis factor-alpha, IL-2, IL-8, IL-10, IL-17, granulocyte colony-stimulating factor monocyte chemoattractant protein, and interferon-inducible protein[ 38 ]. In addition, IL-6 activates numerous downstream signal pathways using creating complexes with its receptor[ 39 ], and also the reason for raised ferritin and C-reactive protein levels, reduced lymphocytes and enhanced neutrophils[ 40 ].…”