Immune checkpoint inhibitors in the post-transplant landscape of hepatocellular carcinoma: A systematic literature review

Background : Immune checkpoint inhibitors (ICIs) have shown promise in the treatment of hepatocellular carcinoma (HCC). However, their safety and efficacy in liver transplant recipients with recurrent HCC remain unclear. This systematic review aims to evaluate the use of ICIs for recurrent HCC after liver transplantation and to identify potential predictive factors associated with graft rejection and treatment response. Methods: A comprehensive literature search was conducted using PubMed and Scopus databases to identify case reports and case series describing the use of ICIs for HCC recurrence after liver transplantation. Data on patient characteristics, treatment details, and outcomes were extracted and analyzed. Results: Twenty-one case reports and case series, involving 39 patients, were included. The median time from liver transplantation to ICI initiation was 24 months. Nivolumab was the most commonly used ICI (59.0%). Among all cases, 25.6% demonstrated a positive response, including stable disease, partial or complete response, while 46.2% experienced progressive disease. Graft rejection occurred in 20.5% of patients, with 50% of these cases resulting in death. Although reported in only some of the cases (17 out of 39), positive PD-L1 expression was associated with a higher risk of graft rejection (66.7%) compared to negative expression (0%). CNI-based immunosuppressive regimens appeared to have lower rejection rates (20%) compared to mTOR inhibitor-based regimens (80%). Conclusions: ICIs show potential for treating recurrent HCC after liver transplantation, but the risk of graft rejection is significant. Careful patient selection, close monitoring, and individualized management of immunosuppression are crucial. Positive PD-L1 expression and the choice of immunosuppressive regimen appear to influence the risk of graft rejection; however, these findings are based on limited data. Prospective studies with larger sample sizes are needed to validate these findings and establish evidence-based guidelines for the use of ICIs in the post-transplant setting.