Immunotherapy for Recurrent Hepatocellular Carcinoma After Liver Transplantation: Current Evidence and Challenges
Stella Vasileiadou, Stavros Neiros, Filippos F. Karageorgos, Athanasios Kofinas, Ifaistion Palios, Nikolaos Antoniadis, Emmanouil Sinakos, Georgios TsoulfasBackground/Objectives: Hepatocellular carcinoma (HCC) frequently develops in the set-ting of chronic liver disease, and liver transplantation (LT) represents the most effective curative option for selected patients. Despite advances in patient selection and surveillance, HCC recurrence after LT remains a major cause of post-transplant mortality and is associated with limited therapeutic options. Immune checkpoint inhibitors (ICIs) have transformed the management of advanced HCC in non-transplant populations; however, their role after liver transplantation remains controversial due to safety concerns and the risk of allograft rejection. This narrative review aims to critically evaluate the current evidence on immunotherapy for recurrent HCC after liver transplantation. Methods: A structured narrative review of PubMed/MEDLINE was conducted through 31 May 2026. Primary clinical reports describing ICI treatment for recurrent HCC after LT were selected using predefined eligibility criteria. Results: Twenty-one primary publications were included, consisting predominantly of case reports and small case series, supplemented by three retrospective cohorts. The reports described heterogeneous oncological outcomes, including occasional durable responses, but progressive disease remained common. Allograft rejection was an important safety concern and was sometimes associated with graft failure and death. More favourable outcomes were observed among some recipients treated at longer intervals after LT; however, this pattern remains hypothesis-generating and may reflect selection and survivor bias, tumour biology, graft stability, and differences in maintenance immunosuppression. Conclusions: ICI treatment for recurrent HCC after LT is associated with uncertain oncological benefit and a clinically important risk of allograft rejection. Its use should be restricted to highly selected recipients following multidisciplinary assessment and, whenever possible, within prospective studies or structured registries.