*Purpose: Mixed hepatocholangiocarcinomas (HCC-CCA) are rare tumors with both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) differentiations. They are usually associated with a worse prognosis than pure HCC tumors however only a few series describing outcomes following liver transplantation (LT) have been reported. We sought to compare post-OLT outcomes of HCC-CCA and HCC in the largest series from the Western hemisphere to date.

*Methods: This is a single-center retrospective cohort study of all consecutive patients with HCC treated with between 1998 and 2018. Patient and tumor characteristics as well as post-LT survival and oncologic outcomes were compared among patients with pure HCC and those with mixed HCC-CCA identified on liver explant.

*Results: A total of 18 HCC-CCA cases were identified and their outcomes compared to 615 pure HCC patients. The median follow-up duration for the cohort was 54 months (IQR 23-103). Both groups were comparable in terms of preoperative findings such as baseline, laboratory and radiological variables. Notable differences however were seen on liver explant pathology, HCC-CCA tumors were significantly more aggressive: 41% were Grade 3 and 41% Grade 4 vs 28 and 16% (p=0.033) of HCC tumors; 60% exhibited microvascular (vs 26%, p=0.006) and 36% lymphatic invasion (vs 5%, p<0.001). Patients with mixed HCC-CCA tumors had a significantly lower 5-year survival rate of 39 vs 75% (p<0.001) as well as a lower 5-year recurrence-free survival rate of 42 vs 87% (p<0.001). Moreover, the time to recurrence was significantly shorter for HCC-CCA patients with a median of 7 (IQR 3 - 8) vs 15 months (IQR 8 - 33) (p=0.004).

*Conclusions: These findings from the largest Western series to date further confirm that mixed HCC-CCA are more aggressive than pure HCC tumors and confer a worse prognosis following liver transplantation.

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