Is COVID-19-induced liver injury different from other RNA viruses?‎

Table 1 Antiviral drugs with a promising efficacy against coronavirus disease 2019 with potential hepatotoxic effect

Drug category	Efficacy and hepatic adverse reactions
Protease inhibitors: lopinavir, ritonavir	They are effective against SARS and MERS but not against COVID-19. These drugs failed to improve the clinical manifestations or shorten the time of conversion to negative test of viral nucleic acids in the bronchoalveolar fluid specimens. They caused increase serum bilirubin and aminotransferases levels in COVID-19 patients.
Viral RNA-dependent RNA polymerase: remdesivir, favipiravir	(1) Remdesivir is an adenine nucleotide analogue used in the management of Ebola virus infection. It inhibits the activity of viral RNA-dependent RNA polymerase. It improves the clinical manifestations of COVID-19 patients presenting with hypoxia with low blood oxygen saturation. It causes a significant increase in AST/ALT in COVID-19 patients; and (2) Favipiravir is a guanosine analogue with a broad-spectrum antiviral activity similar to remdesivir. It is effective against the clinical manifestations and shortening the recovery period of moderate COVID-19 illness. Experimental studies showed that favipiravir increases the serum levels of AST, ALP, ALT and total bilirubin and increased vacuolization in hepatocytes.
Membrane fusion inhibitors: umifenovir	Umifenovir is an indole derivative molecule with broad-spectrum antiviral activity. It is effective in the management of COVID-19, particularly when combined with protease inhibitors. The data are very limited about the hepatotoxicity of umifenovir. Chronic users had high serum transaminases.
Interferon lambda	Endogenous INFλs potentiate the long-term immunity by stimulating T helper 1, cytotoxic T cell and antibody response. It prevents the development of a cytokine storm. Recombinant INFλ may be a promising therapy for COVID-19. There is no clinical evidence that INFλ induces liver injury.

COVID-19: Coronavirus disease 2019; SARS: Severe acute respiratory syndrome; MERS: Middle East respiratory syndrome; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; ALP: Alkaline phosphatase; INFλ: Interferon lambda.