Table 2.
The mechanisms of coronavirus-induced liver injury.
| Pathogenic mechanism | Coronavirus type | References | Highlights |
|---|---|---|---|
| ACE2/DPP4-mediated direct injury of hepatocytes | SARS-CoV | Li et al. (27) | ACE2 was shown to be the functional receptor of SARS-CoV. ACE2 will likely contribute to the development of antivirals and vaccines. |
| SARS-CoV-2 | Bourgonje et al. (28) | ACE2 has been established as the functional host receptor for SARS-CoV-2. ACE2 expression and activity are related to COVID-19 severity. ACE2 inhibitor is a selection of potential treatment modalities for COVID-19. |
|
| MERS-CoV | Wang et al. (29) | The receptor-binding subdomain is critical for viral binding to DPP4 and entry into the target cell. | |
| Immune-mediated injury | SARS-CoV | Duan et al. (68) | IL-1, IL-6, and IL-10 in the serum of SARS patients with abnormal liver function were higher than those in patients with normal liver function. |
| MERS-CoV | Mahallawi et al. (77) | IFN-γ, TNF-α, IL-15, and IL-17 were significantly increased in those infected by MERS-CoV. | |
| SARS-CoV-2 | Huang et al. (38) | TNF-α, IFN-γ, IL-6, IL-8, IL-4, and IL-10 were dramatically elevated in COVID-19 patients. | |
| Thrombosis | SARS-CoV, SARS-CoV-2, and MERS-CoV | Giannis et al. (78) | There was a great proportion of patients with hypercoagulable states after coronavirus infection. |
| SARS-CoV-2 | Llitjos et al. (79) | Elevated D-dimer level and thrombocytopenia were observed in some COVID-19 patients. | |
| Drug hepatotoxicity | SARS-CoV, SARS-CoV-2, MERS-CoV | Sheahan et al. (80) | The anti-corona acitivities of remdesivir has been reported. Redesivir can cause elevation in aminotransferases. |
| SARS-CoV | Cao et al. (81) | Lopinavir/Ritonavir can cause elevation in serum amylase and liver enzymes. | |
| SARS-CoV-2 | Fan et al. (39) | A significantly higher proportion of patients with abnormal liver function had received lopinavir/ritonavir after admission. | |
| SARS-CoV-2 | Xu et al. (82) | Tocilizumabcan cause mild elevation in serum aminotransferase, jaundice and occasional reactivation of hepatitis B. |
ACE2, angiotensin-converting enzyme 2; DPP-4, dipeptidyl-peptidase 4.