Propensity-Matched Analysis of Patients with Mixed Hepatocellular-Cholangiocarcinoma and Hepatocellular Carcinoma Undergoing Liver Transplantation

Mixed hepatocellular-cholangiocarcinomas (HCC-CCAs) are rare tumors with both hepatocellular and biliary differentiation. While liver transplantation (LT) is the gold standard treatment for patients with unresectable hepatocellular carcinoma (HCC), it is contraindicated in known HCC-CCA because of concerns of poor prognosis. We sought to compare posttransplant oncologic outcomes for HCC-CCA and a matched cohort of HCC LT recipients. A retrospective, single-center analysis (1984-2015) identified 12 patients with mixed HCC-CCA who were matched 1:3 to patients with HCC on both pretransplant (radiologic diameter and alpha-fetoprotein) and explant (pathologic diameter, grade/differentiation, and vascular invasion) tumor characteristics. Compared with HCC patients matched on pretransplant characteristics (n = 36), HCC-CCA had higher explant tumor grade, more poorly differentiated tumors, but similar T stage and vascular invasion. HCC-CCA recipients trended toward inferior recurrence-free survival at 5 years (28% versus 61%; P = 0.12) and greater recurrence (HCC-CCA: 50%, median time to recurrence 297 days versus HCC: 22%, median time to recurrence 347 days; P = 0.07). However, when matched to a separate HCC cohort with similar explant pathology, HCC-CCA had similar 5-year recurrence-free survival (42% versus 44%; P = 0.45) and posttransplant recurrence (50% versus 27%; P = 0.13). All 6 HCC-CCA recurrences occurred with poorly differentiated tumors (median survival 21.3 months), without a single recurrence in 5 of the 12 HCC-CCA patients with well-moderately differentiated tumors (median survival 60.2 months). Mixed HCC-CCA tumors are more likely poorly differentiated tumors compared with HCC with similar pretransplant characteristics. However, compared with HCC with similar pathologic characteristics, they display similar recurrence-free survival and are not inherently more aggressive tumors. Low-grade, well-moderately differentiated HCC-CCAs have excellent survival with a low risk for post-LT recurrence, and they should not be excluded from LT. Improved pretransplant identification of pathologic characteristics in HCC-CCA may allow for successful utilization of LT in this subset of patients.