肝细胞癌与肝移植：新辅助和辅助免疫治疗如何？

Immune checkpoint inhibitors (ICIs) have transformed systemic therapy for hepatocellular carcinoma (HCC), leading to growing interest in their integration into liver transplantation (LT) protocols. Their use in the neoadjuvant and adjuvant settings aims to expand transplant eligibility, improve downstaging and/or bridging options, and reduce tumor recurrence. However, the balance between oncologic benefit and immunologic risk, particularly graft rejection, remains a critical challenge. DATA SOURCES: A literature search was conducted on PubMed for articles published up to August 2025. The search keywords included "hepatocellular carcinoma", "liver transplantation", "immune checkpoint inhibitor", "immunotherapy", "neoadjuvant", "adjuvant", "bridging", "downstaging", "immunosuppression", and "washout". Relevant clinical trials, cohort studies, meta-analyses, and case series were included.

Early-phase trials and multicenter cohorts show that pre-LT ICIs achieved downstaging in ∼75%-82%, with radiologic responses up to 94% and pathologic responses 35%-88%. One- and three-year survival after ICI bridging reached ∼95% and 70%-80%, while post-LT survival remained above 85% in 3 years. Rejection risk is substantial: 16%-28% across large series, highest with washouts < 90 days, but largely mitigated with longer intervals. An individual patient data meta-analysis confirmed a 26.4% rejection rate and highlighted washout duration as the key determinant. Adjuvant ICI use post-LT remains limited to case reports, with rejection in ∼25% and mortality in 10%-12%. Novel strategies such as natural killer cell therapy and atezolizumab/bevacizumab combinations show early promise, with recurrence-free survival up to 82% and post-LT survival near 90% in 3 years.

ICIs represent a powerful tool to extend transplant eligibility and improve outcomes in HCC, but their role before and after LT is not yet standardized. Current evidence highlights the importance of patient selection, timing of therapy, and careful management of immunosuppression. Until prospective randomized trials define optimal strategies, ICI integration into transplant practice should remain individualized, multidisciplinary, and confined to experienced transplant centers.