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

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.

Keywords: HCC recurrence; checkpoint inhibitors; liver transplantation; mTOR inhibitors; vascular invasion.

Figure 1

Pre- and post-transplant factors affecting HCC recurrence and post-recurrence survival.Various pre-transplant characteristics may affect the risk of post-transplant HCC recurrence. AFP is a powerful predictor of both recurrence risk and post-recurrence mortality. The immunosuppressive regimen may affect both the risk of neoplasm recurrence and post-recurrence survival. Once recurrence occurs, time to recurrence, pattern of recurrence (and consequently applicable treatments), and residual graft function are the main predictors of mortality. IS: immunosuppression; VI: vascular invasion; AFP alpha-fetoprotein.

Figure 2

Proposed treatment algorithm for HCC recurrence. Recurrence pattern and liver function have a major influence on treatment. Whenever possible, through discussion in a multidisciplinary team, the treatment with the best expected results should be offered, only switching to treatments of lower efficacy if more radical treatments are not applicable. IS: immunosuppression; LT: liver transplantation, HCC: hepatocellular carcinoma, IS: immunosuppression, LF: liver function; TACE: trans-arterial chemoembolization, TARE: trans-arterial radioembolization, BSC: best supportive care; MDT: multidisciplinary team.