P1776 - Practical Consideration for Drug Monitoring of Tacrolimus in Liver Transplant Recipients With SARS-CoV-2 Infection

Monday, October 25, 2021

10:30 AM – 4:15 PM PT

Location: Shoreline Exhibit Hall

Has Audio

Presenting Author(s)

Tejas V. Joshi, MD

Joan C. Edwards School of Medicine, Marshall University
Houston, TX, United States

Tejas V. Joshi, MD¹, Alsadiq Al-Hillan, MD², Fasiha Kanwal, MD, MSHS, FACG³, John Vierling, MD³, Abbas Rana, MD³, John Goss, MD³, Fuad Zain, MBBS³, George Cholankeril, MD³
¹Joan C. Edwards School of Medicine, Marshall University, Houston, TX; ²Baylor College of Medicine/Beaumont Health (Royal Oak) Program, Houston, TX; ³Baylor College of Medicine, Houston, TX

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.

Discussion: 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: Pathophysiologic Mechanisms of Liver Injury in COVID-19

Age/Gender/Status	Time from LT, years	Daily IS	Baseline Trough (ng/mL)	First Trough (ng/mL)	Time to trough, days^a	AST^b (U/L)	ALT^b (U/L)	Change in IS	Second Trough (ng/mL)
56 male, alive	0.26	Tac 9 mg, Pred 15 mg	5.2	14.7	1	13	12	Tac 5 mg, Pred 10 mg	6.4
35 male, alive	0.04	Tac 8 mg, Pred 20 mg	8.1	19.2	1	186	170	Tac 5 mg, Pred 20 mg	11.8
77 male, alive	21.47	Tac 2 mg	3.7	6.9	2	50	32	Tac 2 mg	5.1
72 female, alive	11.80	Tac 2 mg, Pred 5 mg	4.8	18.7	1	19	14	Tac 1 mg, Pred 5 mg	9.0
68 male, alive	4.92	Tac 3 mg	6.8	14.9	3	44	29	Tac 0.5 mg	8.5
66 male, death	2.56	Tac 2 mg	6.0	7.9	3	48	28	Tac 1 mg	9.1
69 male, alive	0.87	Tac 4 mg, Pred 7.5 mg	6.1	7.2	2	21	15	Tac 2 mg, Pred 7.5 mg	3.8
53 female, death	14.76	Tac 10 mg, Pred 5 mg	2.5	6.3	1	28	6	Tac 1.5 mg, Pred 5 mg	2.6
62 male, alive	0.43	Tac 2 mg, Pred 5 mg	5.0	10.8	2	67	72	Tac 1 mg, Pred 5 mg	6.8
63 male, alive	4.28	Tac 2 mg	7.1	9.9	1	61	39	Tac 1 mg	6.9
54 male, alive	4.62	Tac 5 mg	6.5	6.3	1	82	31	Tac 1 mg	4.5
71 male, alive	5.31	Tac 2 mg	3.7	4.1	1	33	40	Tac 2 mg	3.6
60 male, alive	3.68	Tac 3 mg	4.9	11.0	2	20	20	Tac 1 mg	7.9
30 female, death	22.89	Tac 3 mg, Pred 20 mg, MMF 250 mg	6.7	18.4	1	70	66	Tac 0.5 mg, Pred 20 mg	7.4

Table: Tacrolimus-based immunosuppressive management among liver transplant recipients hospitalized with SARS-CoV-2 infection

a Time from positive SARS-CoV-2 PCR nasal swab to tacrolimus trough
b AST and ALT values at time of admission

Abbreviations: ALT, alanine aminotransferase, aspartate aminotransferase, AST; LT, liver transplant; MMF, mycophenolate mofetil; IS, immunosuppression; Pred, prednisone; Tac, tacrolimus

Disclosures:

Tejas Joshi indicated no relevant financial relationships.

Alsadiq Al-Hillan indicated no relevant financial relationships.

Fasiha Kanwal indicated no relevant financial relationships.

John Vierling indicated no relevant financial relationships.

Abbas Rana indicated no relevant financial relationships.

John Goss indicated no relevant financial relationships.

Fuad Zain indicated no relevant financial relationships.

George Cholankeril indicated no relevant financial relationships.

Tejas V. Joshi, MD¹, Alsadiq Al-Hillan, MD², Fasiha Kanwal, MD, MSHS, FACG³, John Vierling, MD³, Abbas Rana, MD³, John Goss, MD³, Fuad Zain, MBBS³, George Cholankeril, MD³. P1776 - Practical Consideration for Drug Monitoring of Tacrolimus in Liver Transplant Recipients With SARS-CoV-2 Infection, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.