(CSPOT12) Effectiveness of everolimus on transplant outcomes in Korean liver transplant recipients: a nationwide cohort study

Background: Liver transplantation (LT) and post-LT immunosuppressive protocols have been vital procedures for the survival of patients with end-stage liver disease. Although everolimus with reduced-dose tacrolimus have been known to offer reduced nephrotoxicity and similar efficacy compared to standard-dose tacrolimus in LT patients, limited evidence is available regarding to the real-world effectiveness in these patients.

Objectives: To evaluate the effectiveness of everolimus on transplant outcomes in Korean LT recipients.

Methods: In a nationwide retrospective cohort study, patients who had undergone their first LT between 2011 and 2020 were identified using the National Health Insurance Service database. The cohort was followed up until the end of 2021 for the development of graft failure, defined as either death or re-transplantation, or acute rejection. Hazard ratios (HRs) were estimated using Cox proportional hazards regression in a propensity score-matched cohort.

Results: Among 4,071‬ matched LT recipients (1,357 everolimus-users and 2,714 non-users), 75.5% and 76.1% were transplanted using living donors with average Charlson comorbidity indexes for orthotopic LT of 1.07 and 1.03, respectively. The incidence rates [95% confidence interval (95% CI)] of graft failure per 100 person-years were 3.09 (2.55–3.63) and 1.32 (1.09–1.56) for the everolimus-users and non-users, respectively. Everolimus use in the real-world was associated with a significantly increased risk of graft failure [adjusted HR (95% CI) = 2.10 (1.64–2.71)], acute rejection [1.61 (1.38–1.89)] and death [2.31 (1.77–3.01)]. However, the risk of re-transplantation was not increased in the everolimus-user group with the adjusted HR (95% CI) of 0.92 (0.46–1.83). The graft-failure survival rate was lower in the everolimus-user group than in the non-user group (p <.0001).

Conclusions: Although everolimus use after liver transplantation did not significantly affect the risk of re-transplantation in Korean liver transplant recipients, it increased the risk of acute rejection and death.