*Purpose: Use of checkpoint inhibitors (CPI) prior to liver transplantation has not been well studied and limited case reports describe a risk of early graft failure secondary to immune mediated hepatic necrosis. However, with CPIs approved as first line therapy for unresectable hepatocellular carcinoma (HCC), the number transplant recipients receiving treatment with CPIs will increase. Therefore, we aimed to explore the association between time from last CPI administration and allograft outcomes in a case series of three liver transplant recipients.

*Methods: We reviewed the charts of patients that received liver transplantation following treatment with checkpoint inhibitor therapy for HCC between January 1, 2018 and November 1, 2020. All transplants were performed with caval sparing technique and received standard three-drug immunosuppression of steroid taper, tacrolimus, and mycophenolate mofetil. Two patients received induction with rATG 3mg/kg. All biopsies were reviewed by a single pathologist and rejection classified by Banff criteria.

*Results: Three patients underwent liver transplantation after receiving CPI therapy for HCC. All three patients received Nivolimab 240mg every 2 weeks the first month, then 480mg every 4 weeks thereafter. Time from last dose of CPI to transplant ranged from 10 days to 3 months. The 2 patients with less than 3 months from last dose of CPI to transplant developed ACR and substantial hepatic necrosis. Patient A’s graft was salvaged after treatment with steroids, 9mg/kg rATG + rituximab. Patient B was re-transplanted for graft failure after failing treatment with steroids, rATG, and plasmapheresis. This patient also developed significant early ACR after re-transplant. Patient C with three months from last dose of CPI to transplant had consistent excellent graft function with no episodes of ACR.

*Conclusions: Pretransplant use of CPI therapy for HCC confers a high risk for acute cellular rejection, antibody mediated rejection and immune mediated hepatic necrosis, which can lead to a high risk of graft loss and patient death. Time from the last dose of CPI to transplant may mitigate the risk for adverse immune mediated outcomes and a waiting period of at least 3 months warrants further evaluation.

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