COVID-19 and Liver Dysfunction: Current Insights and Emergent Therapeutic Strategies

Abstract

The outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has attracted increasing worldwide attention. Cases of liver damage or dysfunction (mainly characterized by moderately elevated serum aspartate aminotransferase levels) have been reported among patients with COVID-19. However, it is currently uncertain whether the COVID-19-related liver damage/dysfunction is due mainly to the viral infection per se or other coexisting conditions, such as the use of potentially hepatotoxic drugs and the coexistence of systemic inflammatory response, respiratory distress syndrome-induced hypoxia, and multiple organ dysfunction. Based on the current evidence from case reports and case series, this review article focuses on the demographic and clinical characteristics, potential mechanisms, and treatment options for COVID-19-related liver dysfunction. This review also describes the geographical and demographic distribution of COVID-19-related liver dysfunction, as well as possible underlying mechanisms linking COVID-19 to liver dysfunction, in order to facilitate future drug development, prevention, and control measures for COVID-19.

Keywords: COVID-19; Liver dysfunction; SARS-CoV-2.

Fig. 1.. Geographical distribution of COVID-19, using the cut-off date for data extraction of March 5, 2020.

Fig. 2.. Proportion of patients with liver dysfunction in Chinese regions: Wuhan and outside Wuhan.

Fig. 3.. Schematic diagram showing the systemic inflammatory response syndrome induced by SARS-CoV2. After the SARS-CoV-2 infection, pathogenic T cells are rapidly activated, producing granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-6 and other proinflammatory factors. GM-CSF will further activate CD14⁺CD16⁺ inflammatory monocytes, producing a larger amount of IL-6 and other proinflammatory factors, and thereby inducing an inflammatory “storm” that leads to immune damage to other organs, such as the lungs and the liver. Both IL-6 and GM-CSF are two key proinflammatory factors that trigger the inflammatory “storm” in patients with COVID-19.