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

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.