Dysregulated liver function in SARS-CoV-2 infection: Current understanding and perspectives

Abstract

Since it was first reported in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread rapidly around the world to cause the ongoing pandemic. Although the clinical manifestations of SARS-CoV-2 infection are predominantly in the respiratory system, liver enzyme abnormalities exist in around half of the cases, which indicate liver injury, and raise clinical concern. At present, there is no consensus whether the liver injury is directly caused by viral replication in the liver tissue or indirectly by the systemic inflammatory response. This review aims to summarize the clinical manifestations and to explore the underlying mechanisms of liver dysfunction in patients with SARS-CoV-2 infection.

Keywords: COVID-19; Cytokine storm; Dysregulated liver function; SARS-CoV-2.

Figure 1

Severe acute respiratory syndrome coronavirus 2 genome and its pathogenesis. A: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome structure and its encoded proteins; B: Virion structure of SARS-CoV-2 illustrating viral structural proteins including spike protein (S), envelope protein (E), membrane protein (M), and nucleocapsid protein (N); C: SARS-CoV-2 entry to the target cells by binding the receptor-binding domain of S protein to cellular receptors, such as angiotensin-converting enzyme 2 and transmembrane protease serine 2. SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; RBD: Receptor-binding domain; TMPRSS2: Transmembrane protease serine 2; ACE2: Angiotensin-converting enzyme 2.

Figure 2

Schematic diagram of the two mechanisms of severe acute respiratory syndrome coronavirus 2-induced liver dysfunction. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes direct liver injury through binding to the angiotensin-converting enzyme 2 receptor and transmembrane protease serine 2 expressed on cholangiocytes and hepatocytes. Indirect injury by cytokine storm. T cells are stimulated to secrete large quantities of cytokines including type I interferons, interleukin-6, and tumor necrosis factor-α following SARS-CoV-2 infection, leading to systemic excessive inflammation syndrome. ACE2: Angiotensin-converting enzyme 2; TMPRSS2: Transmembrane protease serine 2; TNF-α: Tumor necrosis factor-α; IL-6: Interleukin-6; IFN: Interferons.