Acute liver injury in COVID-19 patients hospitalized in the intensive care unit: Narrative review

Figure 1 Pathophysiological mechanisms implicated in the development of coronavirus disease 2019 acute liver injury in the intensive care unit setting. Figure 1 depicts the various pathophysiological mechanisms that come into play in the setting of coronavirus disease 2019 (COVID-19) infection, which eventually culminate in the development of acute liver injury (ALI) in intensive care unit (ICU) patients. Hypoperfusion and ischemia due to the frequently observed hemodynamic instability in the ICU patients play a major role in the process. Passive liver congestion as a result of congestive heart failure of various etiologies is another key determinant. The situation can be further aggravated by ischemia-reperfusion injury. Sepsis can also cause hepatic dysfunction, which is usually cholestatic in nature and reversible, but, when it progresses to septic shock, it results in multiple organ dysfunction syndrome and liver hypoperfusion, manifesting as shock liver. Besides, hypoxia due to respiratory failure and acute respiratory distress syndrome may also lead to ALI. Paradocixally, mechanical ventilation per se can exert deleterious effects on the liver through positive pressure ventilation, especially when accompanied by the application of high positive end-expiratory pressure and large tidal volumes. Furthermore, ALI can stem from the inflammatory cascade generated by the cytokine storm, while it can be further complicated by impaired microcirculation and thrombosis as a result of endotheliitis with concomitant coagulopathy. Drug-induced liver injury, as well as parenteral nutrition, must also not be overlooked as potential causative factors. Finally, liver injury could also be attributed to a direct cytopathic viral effect. There seems to be a complex interplay among these numerous underlying mechanisms, which may act either independently and cause COVID-19 induced ALI in the ICU setting, or more frequently synergistically and generate a relentless ALI vicious cycle.