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

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.

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.

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.

Our results demonstrate that rejection rates were similar in patients receiving ICIs pre-LT and it can be safely managed.