Liver Injury in COVID-19 Patients: An Overview of the Current Evidence

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) preferentially infects cells in the respiratory tract but several studies have also demonstrated low levels of SARS-CoV-2 copies in the liver (Lubnow et al., 2021; Puelles et al., 2020). This is supported by the finding that 14–53% of patients with COVID-19 have evidence of liver dysfunction (Grace et al., 2020), showing abnormal liver test results (Cai et al., 2020). However, the exact cellular site of replication in the liver remained unclear. Studies involving transmission electron microscopy approach showed numerous coronavirus particles in the cytoplasm of hepatocytes. Infected cells displayed a cytopathic phenotype with glycogen granule decrease and canalicular impairment with shedding of microvilli (Y. Wang et al., 2020). SARS-CoV-2 virions were also detected by in situ hybridization methods in vessel lumens and endothelial cells of portal veins of COVID-19 liver samples(Sonzogni et al., 2020).If the viral infection per se is enough to induce liver injury remain to investigate. Liver injury in COVID-19 patients has probably a multifactorial etiology (Figure 1) including the rapid onset of a systemic pro-inflammatory state due to viral infection, the use of potentially hepatotoxic drugs, pneumonia-associated hypoxia and the eventual direct injury of the liver by SARS-CoV-2 (Feng et al., 2020; Zhong et al., 2020).

This book chapter will discuss the potential pathophysiological mechanisms for SARS-CoV-2 hepatic tropism and an overview about the main biochemical and histopathological findings observed in liver from COVID-19 patients. Finally, the effects that this infection can produce in patients with chronic liver disease will be also discussed.

Figure 1.

Potential mechanisms of liver injury in patients with COVID-19

• 1: Cytokine storm, observed in the early phase of COVID-19 infection and is probably the main event altering liver function and integrity. It is characterized by increased interleukin (IL)-2, IL-6, IL-8, IL-1ß, granulocyte colony stimulating factor, interferon-γ inducible protein 10 (CXCL10), monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1α (MIP-1α), and tumor necrosis factor-α (TNF-α);

• 2: COVID-19 patients showing hypoxia and shock caused by respiratory distress syndrome can develop pneumonia-associated hypoxiaand increasing the possibility to suffer from acute liver injury.

• 3: SARC-CoV2 may directly bind to angiotensin converting enzyme II predominantly expressed in cholangiocytes and at lower levels in hepatocytes to dysregulate liver function;

• 4: Drugs including antipyretics, antiviral medications (lopinavir/ritonavir), antibiotics (azithromycin) and anti-inflammatory agents (tocilizumab) may have potential hepatotoxicity and lead to abnormal liver function.