Background aims: Immune checkpoint inhibitors (ICI) are increasingly used in patients with advanced hepatocellular carcinoma (HCC) patients awaiting liver transplantation (LT). However, concerns about the risk of post-transplant rejection persist.

Methods: We conducted an international retrospective cohort study including 119 HCC patients who received ICIs prior to LT. We analyzed the incidence of allograft rejection, graft loss, and post-transplant recurrence with particular focus on the washout period between the last ICI dose and LT.

Results: In this study, 24 of the 119 (20.2%) patients experienced allograft rejection with a median time to rejection of 9 days (IQR 6-10) post-LT. A linear relationship was observed between shorter washout periods and higher rejection risk. Washout periods less than 30 days (OR 21.3, 95% CI: 5.93-103, p<0.001) and between 30 and 50 days (OR 9.48, CI 2.47-46.8, p=0.002) were significantly associated with higher rejection rates in the univariate analysis compared to the washout period above 50 days. Graft loss as a result of rejection occurred in 6 patients (25%) with rejection. No factors related to grafts were associated with rejection. A longer washout period was not associated with a lower recurrence-free survival post-transplantation at 36 months (71 vs. 67%, p=0.71).

Conclusions: Our findings suggest that a washout period longer than 50 days for ICIs before liver transplantation appears to be safe with respect to rejection risk. While these results may help guide clinical decision-making, future prospective studies are essential to establish definitive guidelines.