Liver transplantation for hepatocellular carcinoma following immunotherapy

To explore the emerging use of immune checkpoint inhibitors (ICIs) in hepatocellular carcinoma (HCC) patients eligible for liver transplantation (LT), particularly as bridging and downstaging therapies. This review also addresses the clinical challenges of integrating ICIs into transplant protocols, including graft rejection, immune-related toxicities, and gaps in evidence.

ICIs have shown potential as bridging and downstaging therapies before LT, with multicentric studies reporting 75.6% successful downstaging, 85% 3-year post-LT survival, and 7.2% rejection-related mortality. A washout interval >94 days and older age have been identified as protective factors against allograft rejection. Combining locoregional therapies with ICIs has proven effective in the EMERALD-1 and LEAP-012 trials, which demonstrated improved progression-free survival (15.0 and 14.6 months, respectively) with ICI-TACE combinations. Similarly, the STAR-FIT phase II trial, combining TACE, SBRT, and avelumab, showed a 42% complete response rate and 12% conversion to curative therapy. Toxicity and rejection risk remain major challenges.

ICIs represent a promising tool for expanding transplant eligibility in HCC, but their integration into LT pathways remains complex. Safety concerns, particularly regarding timing and immune modulation, require careful evaluation. Prospective studies and biomarker development are needed to guide clinical decision-making. Novel therapies such as CAR-T cells may offer more targeted approaches in the future.