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

Conclusions and Perspectives

Over the last months, several studies have highlighted the potential role of liver involvement in COVID-19 infection and pathology. In this review, we analysed the published experimental and clinical findings concerning SARS-CoV-2 and previous coronavirus pandemics and proposed mechanisms concerning a putative SARS-CoV-2 hepatic tropism and the interplay between cytopathic and systemic effects in hepatic COVID-19 pathophysiology.

Elevated liver enzymes reflecting hepatic injury are common in COVID-19 patients both with and without chronic liver diseases.[35,38,43,44] Interestingly, while early clinical studies identified significant raises exclusively in serum ALT and AST upon SARS-CoV-2 infection, which reflect hepatocellular damage, recent investigations and metanalyses also highlighted significant increases in ALP and γ-GT and therefore cholangiocellular injury.[35,45] However, it is still not clear whether elevated serum liver biochemistries are causative for the worse outcome, or a consequence of the severe disease course.

In COVID-19 patients without pre-existing hepatic conditions who experienced liver damage, the injury is mostly mild. However, given the central role of the liver in endo- and xenobiotic/drug metabolism, coagulation, albumin and acute phase reactant production, hepatic dysfunction may impact on systemic disease pathophysiology of COVID-19. Long-term follow-up studies are required to explore potential long-term sequels of SARS-CoV-2 infection such as fibrosis.

Crucial questions remain open and need to be answered by future research: Which specific hepatic cells are infected by SARS-CoV-2? Which molecular processes are dysregulated by the infection? What is the real contribution of direct cytopathic effects, cytokine storm, DILI or hypoxia in hepatic dysfunction? By which means could liver injury promote respiratory failure and predispose to a severe course of COVID-19?

The establishment of international registries collecting clinical reports of patients with liver diseases also tested positive for COVID-19, such as the COVID-Hep[175] and the SECURE-Cirrhosis,[176] together with molecular and translational research will surely help us shed some light on these intriguing questions and to set up more effective hepatoprotective programs for future pandemics.