Protective Role of Tacrolimus, Deleterious Role of Age and Comorbidities in Liver Transplant Recipients With Covid-19: Results From the ELITA/ELTR Multi-center European Study

Abstract

Background and aims: Despite concerns that liver transplant (LT) recipients may be at increased risk of unfavorable outcomes from COVID-19 due the high prevalence of co-morbidities, immunosuppression and ageing, a detailed analysis of their effects in large studies is lacking.

Methods: Data from adult LT recipients with laboratory confirmed SARS-CoV2 infection were collected across Europe. All consecutive patients with symptoms were included in the analysis.

Results: Between March 1 and June 27, 2020, data from 243 adult symptomatic cases from 36 centers and 9 countries were collected. Thirty-nine (16%) were managed as outpatients while 204 (84%) required hospitalization including admission to the ICU (39 of 204, 19.1%). Forty-nine (20.2%) patients died after a median of 13.5 (10-23) days, respiratory failure was the major cause. After multivariable Cox regression analysis, age >70 (HR, 4.16; 95% CI, 1.78-9.73) had a negative effect and tacrolimus (TAC) use (HR, 0.55; 95% CI, 0.31-0.99) had a positive independent effect on survival. The role of co-morbidities was strongly influenced by the dominant effect of age where comorbidities increased with the increasing age of the recipients. In a second model excluding age, both diabetes (HR, 1.95; 95% CI, 1.06-3.58) and chronic kidney disease (HR, 1.97; 95% CI, 1.05-3.67) emerged as associated with death CONCLUSIONS: Twenty-five percent of patients requiring hospitalization for COVID-19 died, the risk being higher in patients older than 70 and with medical co-morbidities, such as impaired renal function and diabetes. Conversely, the use of TAC was associated with a better survival thus encouraging clinicians to keep TAC at the usual dose.

Keywords: COVID-19; Liver transplantation; Outcome; Tacrolimus.

Graphical abstract

Figure 1

Flowchart shows the selection of the study population.

Figure 2

Patients with COVID-19 included in the study by country.

Figure 3

Kaplan-Meier survival curve from the date of COVID-19 symptoms (A) overall and (B) stratified by place of management.

Supplementary Figure 1

Kaplan-Meier curves for survival from the date of COVID-19 diagnosis, stratified by age (2 categories) and main immunosuppressant. Cya, cyclosporin A; FK, tacrolimus; mTOR, mammalian target of rapamycin.

Supplementary Figure 2

Kaplan-Meyer curves for survival from the date of COVID-19 diagnosis show the interplay between age of the recipient, primary immunosuppressant, and chronic renal failure (CRF). mTOR, mammalian target of rapamycin.