Risk of transplant rejection associated with ICIs prior to liver transplantation in HCC: A multicenter retrospective study.

BACKGROUND

Studies on the safety of immune checkpoint inhibitors (ICIs) prior to liver transplantation (LT) are still limited to case reports or case series. It is vital to be aware of possible risk of transplant rejection with regards to ICIs after LT.

OBJECTIVE

To explore the possible risk of transplant rejection induced by ICIs in hepatocellular carcinoma (HCC) patients and investigate the safe washout interval between ICIs administration and LT.

METHODS

HCC patients from 3 tertiary hospitals in China who received ICIs prior to LT over the past 5 years were analyzed retrospectively. Patients who had experienced transplant rejection were reported in detail. Additionally, a comprehensive search of databases was conducted to identify case reports of HCC patients who underwent LT after receiving ICIs until October 1, 2024.

RESULTS

In our study, a total of 25 patients were analyzed. Programmed cell death protein 1 (PD-1) inhibitors were most commonly used (68 %, 17/25). The median interval between the last dose of ICIs and LT was 64 (40-150.75) days. Three patients (12 %) experienced T-cell mediated rejection (TCMR), 1 of which was induced by ICIs, and the other 2 of which could not be excluded from the influence of immunosuppressant concentrations. In literature review, a total of 96 cases of HCC patients who had received ICIs prior to LT were included. PD-1 inhibitor monotherapy resulted in significantly higher rejection than PD-L1 inhibitor monotherapy and other ICIs combination regimens (P = 0.021). In patients with pembrolizumab, the interval from ICIs to LT was shorter in the rejection group than in the non-rejection group (P = 0.045). Twenty-one cases (21.88 %) experienced transplant rejection, and 3 patients passed away following transplant rejection.

CONCLUSION

ICIs prior to LT was associated with the risk of transplant rejection, especially with factors such as the type of ICIs and the interval between ICIs and LT. Multicenter prospective studies are needed to further explore the safety of ICIs.