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

SARS-CoV-2 and Hypoxic Hepatitis

Causes for hypoxic hepatitis are multifactorial. In general, cardiac failure, sepsis and respiratory failure account for more than 90% of all cases.[135–138] Additionally, right-sided heart failure was found to aggravate liver injury by liver congestion as a result of elevated central venous pressure.[122,135–140] In cases of long-lasting hemodynamic and/or respiratory failure, hypoxia results in hepatic cell death, histopathologically defined as centrilobular necrosis.[141]

COVID-19-associated ARDS remains the most common complication requiring critical care management including invasive ventilation, high levels of positive end-expiratory pressure (PEEP) and vasoconstrictor therapy in case of hemodynamic instability.[142–145] These factors may be accompanied by right ventricular dysfunction caused by high pulmonary vascular resistance as a result of hypoxaemia and hypercapnia during ARDS.[146,147] Furthermore, COVID-19 causes a hyper-coagulate state with a significant incidence of pulmonary thrombotic complications aggravating acute right-sided heart failure and consequently liver congestion.[148] However, in the majority of cases, SARS-CoV-2 associated liver injury was generally mild and did not exceed >5 times the upper reference limit, therefore not fulfilling the diagnostic criteria for hypoxic hepaitis.[35] These findings were also obtained in critically ill patients referred to the ICU, suggesting that even in cases of severe respiratory failure during SARS-CoV-2 infection, the adequate oxygen supply to the liver is ensured by compensatory mechanisms.[35,36,39,149–154]