Pathophysiological Mechanisms of Liver Injury in COVID-19

Alexander D. Nardo; Mathias Schneeweiss-Gleixner; May Bakail; Emmanuel D. Dixon; Sigurd F. Lax; Michael Trauner


Liver International. 2021;41(1):20-32. 

In This Article

Drug-induced Liver Injury

At the beginning of the COVID-19 outbreak, evidence-based drug therapy was not available. Over the course of 8 months, multiple studies were performed allowing us to give scientifically valid recommendations for the treatment of SARS-CoV-2 infection. In the meantime, various antiviral (remdesivir, lopinavir/ritonavir), antibiotic (macrolids), antimalaria/antirheumatic (hydroxychloroquine), immunomodulating (corticosteroids, tocilizumab) and antipyretic (acetaminophen) drugs have been used in clinical studies or in an off-label fashion. For most of these drugs (eg ritonavir, remdesivir) a hepatotoxic potential has already been confirmed in in vitro/in vivo experiments and in their respective registration studies. Moreover, corticosteroid therapy, which is now recommended by the WHO in patients with severe SARS-CoV-2 infection,[155] is also clearly associated with steatosis or glycogenosis.[156] Recently, the first case of DILI associated with tocilizumab use in a COVID-19 patient has been reported.[62] Tocilizumab undergoes minimal hepatic metabolism, and the most probable etiology for its hepatotoxic effect is the interference with the IL-6 pathway, which plays a key role in hepatic regeneration.[157]