Evaluation of Drug-Induced Liver Injury in Hospitalized Patients with SARS-CoV-2 Infection

Abstract

Elevated liver enzymes are frequently reported in SARS-CoV-2-infected patients. Several mechanisms of liver injury have been proposed, but no clear conclusions were drawn. We aimed to evaluate hepatocellular and cholestatic injury in relation to the administration of potentially hepatotoxic drugs included in the current COVID-19 therapeutic guidelines in a retrospective cohort of 396 hospitalized COVID-19 patients. The main findings of our study are: (1) Significant increase in aminotransferases level was observed during hospitalization, suggesting drug-related hepatotoxicity. (2) Tocilizumab was correlated with hepatocellular injury, including ALT values greater than five times the upper limit of normal. (3) Anakinra was correlated with ALT values greater than three times the upper limit of normal. (4) Younger patients receiving tocilizumab or anakinra had a higher risk of hepatocellular injury. (5) The combination of favipiravir with tocilizumab was associated with AST values greater than three times the upper limit of normal and with an increase in direct bilirubin. (6) The administration of at least three potentially hepatotoxic drugs was correlated with hepatocellular injury, including ALT values greater than five times the upper limit of normal, and with the increase in indirect bilirubin. (7) Remdesivir and favipiravir by themselves did not correlate with hepatocellular or cholestatic injury in our study cohort.

Keywords

• COVID-19
• SARS-CoV-2
• liver injury
• tocilizumab
• anakinra
• favipiravir