Selecting patients with hepatocellular carcinoma for liver transplantation: incorporating tumor biology criteria Víctor Amado, Manuel Rodríguez-Perálvarez, Gustavo Ferrín, Manuel De la Mata Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, IMIBIC, CIBERehd, Córdoba, Spain Abstract: Liver transplantation (LT) is the optimal therapeutic option for patients with liver cirrhosis and hepatocellular carcinoma (HCC). Due to universal donor shortage, only the patients with limited tumor burden (under the so-called Milan criteria) are considered as potential candidates for LT in most institutions. It is expected that in the near future, more liver grafts will be available for patients with HCC due to the implementation of new direct antivirals against hepatitis C, leaving a prone scenario to consider expanding Milan criteria. A moderate expansion of Milan criteria could be implemented without increasing the risk of tumor recurrence if patients with favorable biological behavior are carefully selected. Incorporating information regarding tumor biology in the decision-making algorithm would result in a more rational use of LT in patients with HCC. In the present review, surrogate markers of tumor biology are critically evaluated as potential tools to be combined with existing radiological criteria. In addition, the current state of liquid biopsy is discussed, as this cutting-edge technology may reshape the management of HCC in the upcoming years. Keywords: cell-free DNA, locoregional ablation, alpha-fetoprotein, circulating tumor cells, liquid biopsy, biomarkers