Increased Morbidity and Mortality in COVID-19 Patients with Liver Injury

Abstract

Background There is a high prevalence of liver injury (LI) in patients with coronavirus disease 2019 (COVID-19); however, few large-scale studies assessing risk factors and clinical outcomes in these patients have been done. Aims To evaluate the risk factors and clinical outcomes associated with LI in a large inpatient cohort of COVID-19 patients. Methods Adult patients with COVID-19 between March 1 and April 30, 2020, were included. LI was defined as peak levels of alanine aminotransferase/aspartate aminotransferase that were 3 times the ULN or peak levels in alkaline phosphatase/total bilirubin that were 2 times the ULN. Mild elevation in liver enzymes (MEL) was defined as abnormal peak liver enzyme levels lower than the threshold for LI. Patients with MEL and LI were compared to a control group comprising patients with normal liver enzymes throughout hospitalization. Results Of 1935 hospitalized COVID-19 patients, 1031 (53.2%) had MEL and 396 (20.5%) had LI. Compared to control patients, MEL and LI groups contained proportionately more men. Patients in the MEL cohort were older compared to control, and African-Americans were more highly represented in the LI group. Patients with LI had an increased risk of mortality (relative risk [RR] 4.26), intensive care unit admission (RR, 5.52), intubation (RR, 11.01), 30-day readmission (RR, 1.81), length of hospitalization, and intensive care unit stay (10.49 and 10.06 days, respectively) compared to control. Conclusion Our study showed that patients with COVID-19 who presented with LI had a significantly increased risk of mortality and poor clinical outcomes.

Impact of baseline abnormal liver enzymes in the outcome of COVID-19 infection

“…Interestingly, one previous study from Brazil has also reported much lower frequencies of AST and ALT elevations ( 24 ), but the authors only took those with levels of double the upper limit into account, which are less commonly seen in COVID-19. Indeed, most patients with COVID-19 in the present study, and several other reports had mild abnormalities of AST and/or ALT ( 2 , 4 , 5 , 11 , 14 , 19 , 25 ). The preponderance of abnormal levels of AST over ALT has been reported in several studies ( 4 , 5 , 19 , 22 , 25 ), particularly from the United States ( 14 - 16 , 20 , 26 , 27 ).…”

“…Indeed, most patients with COVID-19 in the present study, and several other reports had mild abnormalities of AST and/or ALT ( 2 , 4 , 5 , 11 , 14 , 19 , 25 ). The preponderance of abnormal levels of AST over ALT has been reported in several studies ( 4 , 5 , 19 , 22 , 25 ), particularly from the United States ( 14 - 16 , 20 , 26 , 27 ). Some studies have reported a parallel increase of ALT and AST suggesting that this concordance may reflect a pattern of liver injury ( 22 ), which could be induced by different mechanisms including drug-induced, aggravation of previous CLD or cholangiocyte and/or endothelial cell dysfunction due to a cytokine storm ( 1 , 2 , 28 , 29 ).…”

“…In the present study, baseline LFT assessed at ED were evaluated prior to the use of most of the aforementioned drugs, but we may not exclude the other commonly prescribed drugs for outpatients with COVID-19, such as analgesics, antipyretics or antibiotics, could have influenced the LFT derangements seen in our patients. Worsening of subjacent CLD seems to be a very unlikely reason for those LFT abnormalities, since they were reported in less than 4% of those affected subjects worldwide ( 16 , 25 , 32 ) and are not so commonly found in the general Brazilian population ( 33 ). It is therefore plausible to hypothesize that uncontrolled inflammation could give rise to abnormal LFT seen in COVID-19.…”

“…ALT, alanine aminotransferase; AST, aspartate aminotransferase; COVID-19, corona virus disease 2019; IU/L, international units per liter; ULN, upper limits of normal.© Translational Gastroenterology and Hepatology. All rights reserved.Transl Gastroenterol Hepatol 2022 | https://dx.doi.org/10.21037/tgh-22-41 study, and several other reports had mild abnormalities of AST and/or ALT(2,4,5,11,14,19,25). The preponderance of abnormal levels of AST over ALT has been reported in several studies(4,5,19,22,25), particularly from the United…”

“…All rights reserved.Transl Gastroenterol Hepatol 2022 | https://dx.doi.org/10.21037/tgh-22-41 study, and several other reports had mild abnormalities of AST and/or ALT(2,4,5,11,14,19,25). The preponderance of abnormal levels of AST over ALT has been reported in several studies(4,5,19,22,25), particularly from the United…”