Systemic Treatment for Hepatocellular Carcinoma Recurrence After Liver Transplantation

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, and liver transplantation (LT) remains the only curative treatment addressing both tumor burden and underlying liver disease. Despite an adequate candidate selection, HCC recurrence after LT occurs in 8-20% of cases and is associated with a poor prognosis, particularly in patients who experience an early relapse. The management of HCC recurrence remains particularly challenging due to the lifelong immunosuppression required after LT, which may promote tumor progression and restrict therapeutic options. This review synthesizes the current evidence on systemic therapies for recurrent HCC after LT, focusing on tyrosine kinase inhibitors (TKIs), immunotherapy, and the current available immunosuppression strategies. Unfortunately, in this setting, robust prospective studies are lacking, and clinical decision-making remains based on retrospective data and expert consensus. Future research should prioritize the prospective evaluation of systemic regimens, integration of immunosuppression modulation, and careful exploration of immunotherapy or new target therapies in this special population.