Immune Checkpoint Inhibitors Before Liver Transplantation May Increase the Risk of Rejection: A Meta-Analysis

Abstract

Abstract Background Immune checkpoint inhibitors (ICI) represent a major breakthrough in cancer immunotherapy. Several molecules have shown efficacy in HCC and are increasingly used as a bridging therapy before liver transplantation. Initial reports have raised concern about severe rejections in patients following ICI therapy. Aims This meta-analysis assesses the risk of neoadjuvant ICI therapy before liver transplantation. Methods We systematically searched MEDLINE, Web of Science and Embase for studies including all patients treated with ICI therapy before liver transplantation from a given center. A random-effects model was applied to pooled results with a priori determined subgroup analyses. Results Eight studies published during the past three years fulfilled all inclusion criteria. All studies are noncomparative case series, one prospective, and seven retrospective. Studies included 52 patients who received various PD1 inhibitors between 1 and 253 days prior to liver transplantation. Patients treated with an ICI ahead of transplantation demonstrated an overall relative risk (RR) of 2.5 [95% CI: 1.4-3.8] for an acute rejection event. Furthermore, a subgroup analysis showed that patients who received PD1 inhibitors up to 30 days (RR 7.2 [95% CI: 4.9-10.5]) or between 30 and 60 days (RR 7.2 [95% CI: 5.1-10.3]) prior to liver transplantation suffered a higher rejection risk than patients with a “washout period” beyond 60 days (RR 1.8 [95% CI: 0.6-4.9]). The ICI, age, and underlying etiology were insignificant for RR in their subgroup analysis. Conclusion PD1 inhibitors within two months of liver transplantation may significantly elevate rejection risk. This meta-analysis provides valuable insights to inform clinical decision-making. Nevertheless, future trials remain imperative to establish definitive guidelines.