*Purpose: Prior studies have suggested that induction therapy leads to worse outcomes after liver transplantation (LT) for hepatocellular carcinoma (HCC). This study evaluated the impact of induction immunosuppression (IS) on post-LT survival and tumor recurrence among patients with T2 HCC nationally.

*Methods: A retrospective cohort of adult LT alone recipients with T2 HCC between 2/27/2002 and 3/31/2019 was identified in the United Network for Organ Sharing database. Time-to-event analyses evaluated the association of induction therapy (none, non-depleting [NDI], depleting [DI]) with overall survival and HCC recurrence (with death as a competing event). Models were stratified by center to prevent confounding by center in a flexible manner, given marked differences in induction practices. Separate multivariable models adjusted for tumor characteristics on last exception application (simulating what is known at the time of induction decision-making) or on explant (simulating the biologic effect of induction).

*Results: The study cohort included 22,535 LT recipients with T2 HCC, of which 17,688 (78.48%) received no induction, 2,984 (13.24%) NDI, and 1,863 (8.27%) DI. Few differences in patient and tumor characteristics were noted between induction groups. Significant center variability in induction use for HCC patients (median 11.71%, IQR: 2.17-45.94%). At LT hospital discharge, three-drug IS was least frequent for the DI group (17.49% vs 52.24% for NDI vs 64.74% for no induction; p<0.001). In adjusted stratified analyses, NDI was associated with improved overall survival accounting for exception tumor features (adjusted HR=0.88 vs no induction, p=0.01; Table). DI was not associated with survival (all p>0.1; Table). The HCC recurrence rate was 5.05% and was not associated with either NDI or DI (all p>0.1; Table).

*Conclusions: Induction IS was not associated with worse post-LT outcomes in patients transplanted for T2 HCC. Similar to the non-HCC population, a small but significant improvement in overall survival was observed with NDI versus no induction in T2 HCC patients.

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