Outcomes of liver transplantation in incidentally diagnosed combined Hepatocellular-Cholangiocarcinoma: A 25-year single-center matched cohort study

Background and aim. Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare liver malignancy, which comprises clinical and morphological features of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) and corresponds to 1–4.7% of cases of primary liver carcinomas. At present, Liver transplantation (LT) is not routinely recommended for known cHCC-CCA due to concerns regarding aggressive behavior and recurrence risk. However, incidental diagnoses after LT performed for presumed HCC raise questions regarding post-transplant outcomes. Material and methods. We conducted a retrospective single-center study including patients who underwent LT between 2000 and 2025. Patients with incidentally diagnosed cHCC-CCA on explant pathology were matched 1 : 2 with HCC controls according to age, year of transplantation, donor type, tumor burden at explant (number and size), lymphovascular invasion, locoregional therapy, and BAR score. Overall survival (OS) and disease-free survival (DFS) were analyzed using Kaplan–Meier estimates and compared with the log-rank test. Results. After matching, 9 patients with cHCC-CCA were matched with 18 HCC controls. Five-year OS was 41.7% in the cHCC-CCA group and 81.5% in the HCC group (p = 0.26) and Five-year DFS was 70% versus 85.9%, respectively (p = 0.25). Recurrence occurred in two patients in each group. To date, this 25-year study represents one of the most rigorously matched European analyses, uniquely incorporating lymphovascular invasion and BAR score as matching variables. Conclusions. Despite the fact that no statistically significant differences were demonstrated in post-transplant survival or recurrence between the groups, worse results could be observed in the studied group, which is consistent with the current non-indication of LT for cHCC-CCA. This study was substantially underpowered, so the absence of statistical significance should not be interpreted as clinical equivalence.

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