Risk Factors of Tumor Recurrence After Liver Transplantation for Combined Hepatocellular Carcinoma and Cholangiocarcinoma

Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) is commonly diagnosed as hepatocellular carcinoma (HCC) preoperatively. Therefore, unexpected recurrence occurs in some patients after liver transplantation (LT). The aim of this study was to identify the risk factors of recurrence. We retrospectively reviewed the data of 20 patients who underwent LT for cHCC-CC from January 2005 to December 2015. Of the 20 patients, 11 (55%) had concurrent HCC and 10 (50%) had multiple cHCC-CCs. Before LT, 13 patients had undergone transarterial chemoembolization (TACE, n = 9), radiofrequency ablation, and TACE (n = 3) or surgical resection (n = 1). Four of the patients (20%) had the classical type, whereas 16 (80%) had subtypes with stem cell features. Six of the 16 patients (37.5%) with subtypes with stem cell features and 3 of the 4 patients (75%) with the classical type showed recurrence after LT. In multivariate analysis, the classical type was significantly associated with poorer recurrence-free survival (RFS) (hazard ratio [HR]: 8.65, confidence interval [CI]: 1.25–60.05, P  = .03) and poorer overall survival (HR: 8.89, CI: 1.37–57.84, P  = .02). Spontaneous tumor necrosis also showed significance on RFS ( P  = .03) among 11 patients with nontreated lesions. In cHCC-CC, the classical type and spontaneous tumor necrosis were associated with recurrence. If these risk factors are found after LT, short-interval follow-up and strategies such as chemotherapy and/or use of mammalian target of rapamycin inhibitors to prevent recurrence are needed.