Pretransplant natural killer cell activity predicts hpatocellular carcinoma recurrence and survival after living donor liver transplantation

Introduction: Natural killer (NK) cells play a crucial role in innate immune defense and tumor surveillance after liver transplantation (LT). However, the prognostic value of pre-transplant NK cell activity in living donor LT (LDLT) remains unclear. This study aimed to investigate whether pre-transplant NK cell activity is associated with post-transplant outcomes, including overall survival (OS) and recurrence-free survival (RFS) in hepatocellular carcinoma (HCC) recipients.
Method: A total of 134 adult patients who underwent LDLT between January 2020 and December 2023 at Seoul St. Mary’s Hospital, The Catholic University of Korea, were retrospectively analyzed. Pre-transplant NK cell activity was measured using interferon-γ release assays and classified as low (<10 pg/mL) or high (≥10 pg/mL). OS was analyzed inthe entire cohort, and RFS was assessed in the 70 patients with HCC. Survival analyses were performed using Kaplan-Meier curves with log-rank tests and multivariate Cox proportional hazards models.
Results: Patients with high NK activity (≥10 pg/mL) showed superior overall survival compared with those with low activity (log-rank p = 0.032). In multivariate analysis, high NK activity independently predicted better overall survival (HR, 0.58; 95% CI, 0.31-0.91; p =0.044). Among HCC recipients, those with high NK activity demonstrated significantly improved recurrence-free survival (log-rank p = 0.004). Multivariate Cox regression confirmed NK activity as an independent predictor for tumor recurrence (HR, 0.27; 95% CI,0.08-0.87; p = 0.028), while tumor size ≥5 cm was associated with higher recurrence risk(HR, 3.88; 95% CI, 1.18-12.69; p = 0.025).
Conclusions: Pre-transplant NK cell activity is an independent prognostic factor for both survival and HCC recurrence after LDLT. High NK activity reflects favorable immunologic competence and may serve as a simple and practical biomarker for risk stratification in liver transplant recipients.