Safety of Immune Checkpoint Inhibitors Prior to Liver Transplantation in Hepatocellular Carcinoma

BACKGROUND: Immune checkpoint inhibitors (ICIs) have emerged as promising agents for the management of advanced HCC. By reducing tumour burden, ICIs may serve as a downstaging/bridging tool to improve transplant candidacy. The aim of this study was to assess the safety of patients receiving pre-LT ICIs. METHODS: Multicenter, retrospective cohort study from January 2018 to December 2024, including 48 patients who received ICIs prior to LT (ICI cohort). A control cohort (non-ICI cohort) was built (1:3) using propensity score matching including 144 patients who underwent LT for HCC without prior ICI. RESULTS: Within the ICI cohort (N = 48) rejection occurred in 9 patients (18.8%), all biopsy-proven, with a median onset of 31 days post-LT (12.0-182.0). The median washout period was 60 days (13-96). Patients experiencing rejection had shorter washout periods (p = 0.029). All rejection episodes were successfully managed; two were steroid-resistant, one requiring re-transplantation. There were no rejection-related deaths. Of the 5 patients with HCC recurrence, 60% received ICI for < 90 days (p = 0.027). Comparison between the ICI and non-ICI cohort revealed no significant differences in rejection rates (18.8% vs. 19.4%, p = 0.916), graft failure, HCC recurrence, or overall mortality. Overall survival (OS) did not differ between ICI and non-ICI patients (p = 0.625) or between those with and without rejection (p = 0.119). Rejection was not associated with increased mortality, with deaths primarily attributed to infection or HCC recurrence. CONCLUSION: Our results demonstrate that rejection rates were similar in patients receiving ICIs pre-LT and it can be safely managed.