Abstract
Background: There is limited evidence on safety and efficacy on immunotherapy use before and after liver transplantation.
Methods: A literature review was performed to identify patients who received immunotherapy before and after liver transplantation. We reviewed the rejection rate and risk factors of rejection. In patients treated for hepatocellular carcinoma (HCC), the oncological outcomes were evaluated including response rate, progression-free survival and overall survival.
Results: We identified 97 patients from 41 publications. The rejection rate was 36% (n = 35), and graft loss occurred in 11 patients (11%). Forty-four patients received immunotherapy before undergoing a liver transplantation. Among them patients who experienced rejection were transplanted earlier following their last dose of immunotherapy, with a median time of 2.9 weeks compared to 8.3 weeks in patients without rejection (p<0.001). Fifty-three patients had a prior liver transplantation and subsequently received immunotherapy. Among them patients who developed acute rejection received immunotherapy earlier after transplantation, with a median duration of 2.9 years compared to 4.0 years in patients without rejection (p = 0.04). Graft Programmed death-ligand 1 (PD-L1) positivity was more frequent among patients with acute rejection (100% vs. 0%) (p=0.005). In patients treated for recurrent HCC, those with treatment response were patients who received treatment at a later interval from transplant (median time of 4.5 vs. 2.2 years, p=0.02).
Conclusions: Rejection risk remains the major obstacle to immunotherapy use for patients with liver transplant. Shorter interval between immunotherapy and transplant are associated with increased risk of acute rejection.