Reappraising Liver Transplantation for Combined Hepatocellular-cholangiocarcinoma

OBJECTIVE: To determine whether liver transplantation (LT) confers durable oncologic benefit in combined hepatocellular-cholangiocarcinoma (cHCC-CCA) and to identify predictors of recurrence that may guide transplant candidacy. BACKGROUND: cHCC-CCA is a rare primary liver malignancy with aggressive biological behavior. LT has traditionally been contraindicated due to concerns regarding recurrence. We evaluated long-term outcomes of LT versus liver resection (LR) and compared LT outcomes for cHCC-CCA with those for hepatocellular carcinoma (HCC). METHODS: Patients with cHCC-CCA who underwent LT or LR between 2010 and 2024 were identified from a prospective database. Survival outcomes, recurrence patterns, and risk factors for recurrence were analyzed. Outcomes of LT for cHCC-CCA were additionally compared with HCC. RESULTS: A total of 79 patients underwent LT (diagnosed on explant) and 32 underwent LR for cHCC-CCA. 5-year overall survival (OS) and recurrence-free survival (RFS) were superior following LT compared with LR (OS: 89.9% vs. 65.6%, P=0.007; RFS: 84.8% vs. 53.1%, P=0.001). This benefit was maintained for tumors within UCSF criteria [overall survival (88.7% LT vs. 65.6% LR, log rank P 0.014) and RFS (89.8% LT vs. 51.6% LR, P<0.001)]. Among LT recipients, OS for cHCC-CCA was comparable to HCC (89.9% vs. 86%, P=0.721). Within the LT cohort, macrovascular invasion (HR 25.01, P=0.003) and poor tumor differentiation (HR 7.29, P=0.004) independently predicted recurrence. CONCLUSION: In carefully selected patients, cHCC-CCA within UCSF criteria can achieve transplant outcomes comparable to HCC. Macrovascular invasion and poor tumor differentiation are major predictors of recurrence and may inform candidate selection for LT.