S1140 Practical Consideration for Drug Monitoring of Tacrolimus in Liver Transplant Recipients With SARS-CoV-2 Infection

Abstract

Introduction: Previous studies have shown that infection-related cytokine increase of interleukins can cause suppression of cytochrome P450.. SARS-CoV-2 infection has been associated with increased cytokine levels which may suggest suppression of CYP3A4 enzymes and downstream interaction with CYP-mediated drug metabolism including calcineurin inhibitors. Tacrolimus is a calcineurin inhibitor metabolized via CYP3A4. This potential effect of CYP3A4 inhibition on immunosuppression management with tacrolimus in liver transplant recipients with SARS-CoV-2 infection has yet to be evaluated. Methods: We retrospectively evaluated data between June 1, 2020 through December 31, 2020. All patients had confirmed SARS-CoV-2 and among those on tacrolimus-based therapy, serial tacrolimus trough levels were collected during the hospitalization were analyzed. Results: 18 OLT recipients were hospitalized with SARS-CoV-2.14 patients had tacrolimus trough levels throughout hospitalization, 12 of which were on stable immunosuppression therapy. 9 (64.3%) patients had elevated liver enzymes at time of admission. All patients experienced a decrease in baseline albumin levels and 7 out of 10 had an elevated ferritin level within 72 hours from admission.13 (92.8%) patients on tacrolimus had an increase from their baseline levels after testing positive, with an average increase of 105.6% (SD, 81%.7). 9 patients (64.3%) had at least a 50% increase from baseline trough levels. Among these patients, tacrolimus dose was subsequently reduced by an average of 45%. Steroid use did show a positive correlation (Pearson coefficient=0.57, P=0.03) with a rise above baseline tacrolimus trough. Conclusion: We found that most patients on tacrolimus had a supratherapeutic trough goals. There was an average two-fold increase in tacrolimus trough levels compared to baseline, with 64% (n=9) of patients experiencing at least a 50% increase. As expected, these supratherapeutic levels in trough levels in the setting of SARS-CoV-2 infection led to considerable change in immunosuppressive therapy with an approximately 50% reduction in daily tacrolimus dosing. These observations may suggest that SARS-CoV-2 infection in liver transplant recipients should be taken into special consideration when managing immunosuppression. This is the first study to describe these findings. Our study provides compelling evidence to closely monitor tacrolimus levels during acute infection and adjust dosing accordingly.Figure 1.: Pathophysiologic Mechanisms of Liver Injury in COVID-19Table 1.: Characteristics of Patients with Cirrhosis and Clinically Significant Portal Hypertension (CSPH) Based on SARS-CoV-2 Infection. Abbreviations: IQR, interquartile range; BMI, body mass index; CAD, coronary artery disease; BMI, body mass index; MELD-Na, Model for End-stage Liver Disease; CTP, Child Turcotte Pugh; HgbA1C, hemoglobin A1c; COPD, chronic obstructive pulmonary disease