Acute-on-chronic liver failure in patients with severe acute respiratory syndrome coronavirus 2 infection

Table 1 Summary of the relationship between the pathophysiologic mechanism of a virus and its possible clinical impact in the context of liver damage caused by severe acute respiratory syndrome coronavirus 2

Pathophysiologic mechanism of virus	Clinical impact	Considerations for clinical management
Direct influence of the virus on the liver cells	Significant ACE2 expression in parenchymal liver cells contributing to virulence and further damaging effect of the virus on the cells	Several antiviral agents are approved for treatment of SARS-CoV-2 infection e.g. remdesivir and ritonavir-boosted nirmatrelvir, which can inhibit viral replication. Also, monoclonal antibodies reduce the binding ability of SARS-CoV-2 to the ACE2 receptor
Drug-induced liver injury	Drug metabolized by cytochrome P-450 could contribute to secondary toxicity of several drugs (paracetamol, antibiotics)	Following the strict rules for avoidance of hepatotoxic drugs if possible. Standard use of hepatoprotective medications
Results of systemic inflammation response and general hypoxia	The hypoxic damage of hepatocytes, platelet activation, endotheliopathy, immune-mediated response related to liver damage	Administration of corticosteroids and other immunomodulators can reduce or modulate the adverse impact of immune over-response
Role of immunity	Impaired synthesis of PRRs are toll-like receptors, activation of the pro-inflammatory cytokines such as IL-1, IL-6, TNF-alpha	Use of IL-1 and IL-6 inhibitors, such as anakinra or tocilizumab, as well as Janus kinase inhibitors, such as baricitinib, can decrease the excessive effect of pro-inflammatory cytokines

ACE2: Angiotensin-converting enzyme 2; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; IL-6: Interleukin 6.