Significant Liver Injury During Hospitalization for COVID-19 Is Not Associated With Liver Insufficiency or Death

Abstract

Background and Aims COVID-19 is associated with hepatocellular liver injury of uncertain significance. We aimed to determine whether development of significant liver injury during hospitalization is related to concomitant medications or processes common in COVID-19 (e.g. ischemia, hyperinflammatory or hypercoagulable states) and to determine whether it can result in liver failure and death. Methods 834 consecutive patients hospitalized with COVID-19 were included. Clinical, medication and laboratory data were obtained at admission and throughout hospitalization using an identified database. Significant liver injury was defined as an AST≥ 5X ULN; ischemia was defined as vasopressor use for a minimum of 2 consecutive days; hyper-inflammatory state as hs-CRP ≥100mg/L and hypercoagulability as D-dimer ≥5mg/L, any time during hospitalization. Results 105 (12.6%) patients developed significant liver injury. Compared to those without significant liver injury, ischemia [OR 4.3 (2.5-7.4, p <0.0001)] and tocilizumab use [OR 3.6 (1.9-7.0, p=0.0001)] were independent predictors of significant liver injury. While AST correlated closely with ALT (R=0.89) throughout hospitalization, AST did not correlate with INR (R= 0.10) or with bilirubin (R=0.09). Death during hospitalization occurred in 136 (16.3%) patients. Multivariate logistic regression showed that significant liver injury was not associated with death [OR 1.4 (0.8-2.6, p=0.2)], while ischemic [OR 2.4 (1.4-4.0, p=0.001)] hypercoagulable [OR 1.7 (1.1-2.6, p=0.02)], and hyperinflammatory [OR 1.9 (1.2-3.1, p=0.02)] disease states were significant predictors of death. Conclusions Liver test abnormalities known to be associated with COVID-19 are secondary to other insults, mostly ischemia or drug-induced liver injury, and do not lead to liver insufficiency or death.

Prevalence and Prognostic Impact of Deranged Liver Blood Tests in COVID-19: Experience from the Regional COVID-19 Center over the Cohort of 3812 Hospitalized Patients

“…However, other authors did not find consistent correlation between elevated AST and markers of muscle injury, leading to conclusion that the liver was the most likely source of elevated LBTs [ 4 ]. This liver lesion seems not to be clinically significant in majority of cases, as liver failure develops only exceptionally, usually among the patients with already compromised liver function due to existing cirrhosis, or as the part of multiorgan failure in most severe cases of COVID-19 [ 6 , 7 , 17 ].…”

“…Conflicting data have been published regarding the prognostic impact of elevated LBTs. Whereas in some studies, elevated LBTs were associated with more severe clinical presentation but they were lacking follow-up data to analyze mortality, and others reported various associations to ICU admission, need for mechanical ventilation and death [ 5 , 7 , 10 , 11 , 12 , 13 , 14 , 25 ]. In the study conducted over the 1827 hospitalized patients in United States, higher risk of dying was observed only among patients with elevated baseline bilirubin, whereas both elevated bilirubin and AST as recorded at the peak hospitalization were associated with death, and other LBTs were not [ 25 ].…”

“…A total of 3390 (88.9%) patients had pneumonia at admission, and of them 3136 (82.3%) required oxygen supplementation. Median length of hospitalization was 10 days IQR (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). Rates of ICU admission, need for HFNC oxygenation and MV were 23.1%, 19.9% and 17.3%, respectively.…”

“…Whereas elevation of aminotransferases has been commonly seen in hospitalized patients with COVID-19, liver failure represents a rare development usually encountered among patients with already known liver cirrhosis, or as the part of multiorgan failure caused by severe inflammatory response syndrome and septic shock [ 4 , 5 , 6 , 7 , 8 , 9 ]. In some previous reports deranged liver blood tests (LBT) were associated with more severe forms of COVID-19 and adverse clinical outcomes, although not all the authors came to the same conclusion [ 10 , 11 , 12 , 13 , 14 ].…”

Liver Injury in Severe COVID-19 Disease: Need a Closer Look!

“…We read with great interest the study by Chew et al 1 concluding that liver test abnormalities associated with COVID-19 per se do not lead to liver insufficiency or death. Whereas, COVID-19-related ischemic, hypercoagulable, and hyperinflammatory disease states are significant predictors of death.…”