Therapeutic Approach to Post-Transplant Recurrence of Hepatocellular Carcinoma: Certainties and Open Issues

Simple Summary Hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) results in a relevant worsening of the prognosis of transplanted subjects. Pre-transplant HCC characteristics are the main determinants of the risk of recurrence and various tools exist to estimate recurrence risk. Once recurrence has occurred, the pattern of recurrence greatly influences whether the patient is a candidate for curative treatment and consequently significantly impacts prognosis. We reviewed different predictive models of post-transplant recurrence, the role of immunosuppression, and the efficacy and feasibility of various therapeutic approaches.Abstract Hepatocellular carcinoma (HCC) is a growing indication for liver transplantation (LT). Careful candidate selection is a prerequisite to keep post-LT recurrence rates within acceptable percentages. In the pre-LT period, various types of locoregional treatments and/or systemic therapies can be used for bridging or downstaging purposes. In this context, one of the factors limiting the possibility of treatment is the degree of functional liver impairment. In the LT subject, no widely accepted indications are available to guide treatment of disease recurrence and heterogeneity exists between transplant centers. Improved liver function post LT makes multiple therapeutic strategies theoretically feasible, but patient management is complicated by the need to adjust immunosuppressive therapy and to assess potential toxicities and drug-drug interactions. Finally, there is controversy and uncertainty about the use of recently introduced immunotherapeutic drugs, mainly due to the risk of organ rejection. In this paper, we will review the most recent available literature on the management of post-transplant HCC recurrence, discussing evidence and controversies.