High immunosuppressants variability adversely affects post-transplant recurrence for patients with hepatocellular carcinoma

Abstract

Tumor recurrence after liver transplantation (LT) for hepatocellular carcinoma (HCC) is the most significant obstacle impacting the prognosis of patients. Managing the clinical application of immunosuppressive agents is difficult, owing to their limited therapeutic range and notable intrapatient variability (IPV). In this study, we explored the association between the IPV of different immunosuppressants and LT outcomes according to HCC. The study retrospectively analyzed 242 patients with HCC undergoing LT between January 2015 and December 2020. We initially stratified the administration of sirolimus into two groups to observe its impact on post-transplant prognosis. Subsequently, we investigated the influence of high and low immunosuppressant IPV on patient outcomes within each group. Overall survival in patients was significantly increased with sirolimus compared with patients solely receiving tacrolimus ( P < 0.05), especially among patients beyond the Hangzhou criteria ( P < 0.0001). High IPV was defined as a coefficient of variance > 30%. Patients with HCC who exhibited high tacrolimus IPV had markedly lower 5-year recurrence-free survival (73% vs 47%; P < 0.05). Tacrolimus IPV is not applicable to patients using mTOR inhibition to predict post-transplant recurrence. Sirolimus IPV serves as an effective predictor of post-transplant prognosis. Patients with HCC who exhibited high sirolimus IPV had markedly lower 5-year recurrence-free survival (73.7% vs 50.0%; P < 0.05). Multivariable analysis confirmed the independent association between high sirolimus IPV and recurrence-free survival (hazard ratio, 2.636; 95% confidence interval, 1.159–5.998). IPV of immunosuppressants effectively predicts prognosis in patients with HCC undergoing LT; however, using tacrolimus IPV is not applicable to patients undergoing mTOR inhibition. Using post-LT surveillance of sirolimus concentration could effectively assess the risk of tumor recurrence.