Molecular mechanisms underlying SARS-CoV-2 hepatotropism and liver damage

Abstract

In coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) primarily targets the respiratory system, but evidence suggests extrapulmonary organ involvement, notably in the liver. Viral RNA has been detected in hepatic tissues, and in situ hybridization revealed virions in blood vessels and endothelial cells. Electron microscopy confirmed viral particles in hepatocytes, emphasizing the need for understanding hepatotropism and direct cytopathic effects in COVID-19-related liver injury. Various factors contribute to liver injury, including direct cytotoxicity, vascular changes, inflammatory responses, immune reactions from COVID-19 and vaccinations, and drug-induced liver injury. Although a typical hepatitis presentation is not widely documented, elevated liver biochemical markers are common in hospitalized COVID-19 patients, primarily showing a hepatocellular pattern of elevation. Long-term studies suggest progressive cholestasis may affect 20% of patients with chronic liver disease post-SARS-CoV-2 infection. The molecular mechanisms underlying SARS-CoV-2 infection in the liver and the resulting liver damage are complex. This “Editorial” highlights the expression of the Angiotensin-converting enzyme-2 receptor in liver cells, the role of inflammatory responses, the impact of hypoxia, the involvement of the liver's vascular system, the infection of bile duct epithelial cells, the activation of hepatic stellate cells, and the contribution of monocyte-derived macrophages. It also mentions that pre-existing liver conditions can worsen the outcomes of COVID-19. Understanding the interaction of SARS-CoV-2 with the liver is still evolving, and further research is required.

Keywords: SARS-CoV-2; COVID-19; Hepatotropism; Angiotensin-converting enzyme-2

Core Tip: The hepatotropism of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a growing concern amid the coronavirus disease 2019 (COVID-19) pandemic. Despite its respiratory focus, the virus significantly affects various organs, notably the liver, leading to complications like inflammation, abnormal function tests, and, in severe cases, organ damage. This complex involvement worsens disease outcomes. Understanding the virus's interplay with the liver, mediated by the Angiotensin-converting enzyme-2 receptor, is crucial for tailored treatments. The liver's pivotal role in the immune response emphasizes the need to comprehend SARS-CoV-2 hepatotropism. Ongoing research is vital for uncovering mechanisms, clinical implications, and effective strategies in managing COVID-19 patients with liver involvement.