Incidental Combined Hepatocellular-Cholangiocarcinoma in Liver Transplant Recipients: A Matched Cohort Study

Mixed hepatocellular carcinoma (HCC) with cholangiocarcinoma (HCC-CCA) is an aggressive primary liver cancer and difficult to distinguish from HCC using non-invasive methods. Outcomes of patients incidentally diagnosed with HCC-CCA after LT relative to pure HCC with similar tumor burden were investigated. Medical records of patients undergoing LT (n = 1,898) for HCC (n = 493) from 6/2008-9/2023 were reviewed. Patients incidentally diagnosed with HCC-CCA were propensity matched to HCC patients undergoing LT. Independent analyses were performed using pre-LT (Match1; identifiable pre-LT) and explant pathology (Match2, more prognostic) characteristics. Incidental HCC-CCA occurred in 19 (3.9%) patients; all assumed to have HCC pre-LT and received HCC-directed neoadjuvant treatment. When matched on pre-LT characteristics (Match1, n = 57), more patients with HCC-CCA were outside Milan or University of California, San Francisco criteria on explant (p = 0.01). More patients with HCC-CCA underwent neoadjuvant microwave ablation (p = 0.02) compared to HCC Match2 (n = 45) but were otherwise similar demographically and clinically. Overall and recurrence-free survival were lower for HCC-CCA in Match1 (p = 0.003 and p < 0.001, respectively) and Match2 (p < 0.001 and p = 0.001, respectively). HCC-CCA has an aggressive phenotype with high recurrence after LT. Better screening tools and biomarkers are needed to distinguish HCC-CCA from HCC to ensure patients receive appropriate treatment and maximize post-LT outcomes.