Pretransplant Immune Checkpoint Inhibitor Treatment for Intermediate-advanced Hepatocellular Carcinoma in Living Donor Liver Transplantation

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Background: The use of immune checkpoint inhibitors (ICIs) as a downstaging or bridging therapy for liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) is gaining momentum. However, evidence regarding the feasibility and safety of pre-LT ICI therapy remains limited and controversial. This study presents our experience with patients with intermediate-advanced HCC who were downstaged using regimens incorporating ICIs and subsequently underwent living donor LT. Methods: We retrospectively reviewed the medical records of 10 patients with Barcelona Clinic Liver Cancer stage B or C HCC treated with locoregional therapies (LRTs), ICIs, and living donor LT at Chang Gung Memorial Hospital at Linkou between 2021 and 2024. Results: In total, 10 recipients received pre-LT ICI-based downstaging therapy, with 8 also undergoing concomitant LRTs. Two patients experienced grade III immune-related hepatitis. The median ICI washout period before LT was 149 d. Posttransplantation, 5 patients developed allograft rejection, which was managed effectively with routine steroid therapy. Notably, 4 patients demonstrated a complete pathological response. After a median post-LT follow-up of 15.5 mo (interquartile range, 8-25 mo), 2 patients experienced tumor recurrence. The 12- and 24-mo overall survival rates post-LT were 75%. Conclusions: Selected patients with advanced, initially untransplantable HCC can benefit from a multimodal approach involving LRTs combined with ICIs, enabling successful LT. These findings suggest a potential paradigm shift in the treatment of intermediate-advanced HCC, warranting further investigation in larger cohorts and longer-term studies.

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