Liver Transplantation for Hepatocellular Carcinoma

Abstract

Objective: To establish the significance of complete pathologic response (cPR) on survival and locoregional treatment outcomes in a large US cohort. Background: cPR in hepatocellular carcinoma (HCC) is associated with improved post–liver transplant (LT) outcomes. cPR rates, modality-specific differences, and predictors remain undefined. Materials and Methods: Patients were identified from the United Network for Organ Sharing (UNOS) database (2012–2024). cPR was defined as the absence of a viable tumor on explant pathology. Logistic regression identified predictors of cPR, Fine-Gray models estimated the incidence of cPRand Kaplan-Meier analysis assessed survival. Results: Among 7398 LT recipients, 2167 (29.3%) achieved cPR. Imaging–pathology concordance was poor (30.5%), with imaging overestimating response in 42.6% of cases (κ=0.17, P <0.001). Longer waitlist time [>18 vs. <6 mo; odds ratio (OR): 1.94, 95% CI: 1.57–2.40], Y-90 (41.2%), and ablation (36.4%) were associated with higher cPR rates than transarterial chemoembolization (24.0%; P <0.001). On multivariable analysis, yttrium-90 (Y-90) [adjusted OR (aOR): 1.89, 95% CI: 1.46–2.05] and ablation (aOR: 1.23, 95% CI: 1.08–1.39) independently increased cPR, whereas greater tumor burden and elevated alpha-fetoprotein reduced cPR. Y-90 benefit was greatest when administered ≤6 months of waitlisting (OR: 2.40, 95% CI: 1.59–3.61) and in all-comer candidates (OR: 1.58, 95% CI: 1.17–3.26). Fine-Gray analysis confirmed the highest cumulative incidence of cPR with Y-90 across transplant eligibility criteria. cPR was associated with improved 5-year overall survival (86.6% vs. 77.4%) and recurrence-free survival (76.9% vs. 63.1%; P <0.001). Conclusions: Nearly one-third of LT recipients with HCC achieved cPR, which was associated with improved survival. Y-90 was independently associated with higher cPR rates, particularly when administered early and among patients with higher tumor burden.