Presence of cholestasis and its impact on survival in SARS-CoV-2 associated acute respiratory distress syndrome

Abstract

Data on cholestasis and biliary injury in patients with COVID-19 are scarce. The primary aim of this study was to evaluate the prevalence of cholestasis and factors associated with its development and outcome in critically ill patients with COVID-19 associated acute respiratory distress syndrome (ARDS). In this retrospective exploratory study, COVID-19 patients with ARDS admitted to an intensive care unit (ICU) at the Medical University of Vienna were evaluated for the development of cholestasis defined as an alkaline phosphatase level of 1.67x upper limit of normal for at least three consecutive days. Simple and multiple logistic regression analysis was used to evaluate parameters associated with development of cholestasis and survival. Of 225 included patients 119 (53%) developed cholestasis during ICU stay. Patients with cholestasis had higher peak levels of alkaline phosphatase, gamma-glutamyl transferase, bilirubin and inflammation parameters. Factors independently associated with cholestasis were extracorporeal membrane oxygenation support, ketamine use, high levels of inflammation parameters and disease severity. Presence of cholestasis and peak ALP levels were independently associated with worse ICU and 6-month survival. Development of cholestasis is a common complication in critically ill COVID-19 patients and represents a negative prognostic marker for survival. It is associated with disease severity and specific treatment modalities of intensive care.

Keywords: COVID-19; Cholestasis; ICU; Ketamine; Liver injury.

Fig. 1

Liver and inflammatory parameters in critically ill COVID-19 patients according to cholestasis development. Comparison of liver chemistries (ALP, γGT, bilirubin, AST and ALT) and inflammatory parameters (CRP, IL-6 and PCT) between patients with (red) and without cholestasis (blue) at three different time points (i.e. admission, peak values and discharge/death) as indicated. Bars represent median values; vertical lines indicate interquartile range.

Fig. 2

Liver and inflammatory parameters in critically ill COVID-19 patients according to ICU survival. Comparison of liver chemistries (ALP, γGT, bilirubin, AST and ALT) and inflammatory parameters (CRP, IL-6 and PCT) between ICU survivors (red) and ICU non-survivors (blue) at three different time points (i.e. admission, peak values and discharge/death) as indicated. Bars represent median values; vertical lines indicate interquartile range.