Managing hepatocellular carcinoma recurrence after liver transplantation: emerging role of immune checkpoint inhibitors.

Despite adherence to transplantation selection criteria, such as the Milan criteria, hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) occurs in 8-20% of cases. This highlights the need for improved patient selection strategies and better post-LT management to mitigate recurrence risks. This narrative review explores current approaches for managing HCC recurrence post-LT, with a focus on immune checkpoint inhibitors (ICIs). Surgery or locoregional therapies are preferred but are often unsuitable for disseminated disease, leaving systemic therapies-including tyrosine kinase inhibitors (TKIs) such as sorafenib, lenvatinib, and regorafenib-as primary options. Although ICIs have shown promise in advanced HCC and are increasingly used in LT settings, evidence for their post-LT application remains limited to case reports and series. Post-LT care is especially challenging due to the concurrent use of immunosuppressants, requiring a balance between managing acute rejection and administering ICI agents. This dual approach necessitates identifying biomarkers to predict ICI efficacy and allograft rejection. Key strategies may include using anti-CTLA-4 agents with potentially lower rejection rates, delaying ICI initiation post-LT, and optimizing combination immunosuppression regimens centered on tacrolimus. However, ICIs should be reserved for select cases or clinical trials, with multidisciplinary team collaboration being critical. Prospective studies are needed to establish clear guidelines for their use in post-LT care.