**7.2 Immunosuppressive strategies after liver transplantation for HCC**

The optimal immunosuppressive regimen for post-transplant HCC patients remains a subject of debate and research. In the patients transplanted for HCC within Milan criteria and without high risk features on explants' pathology, i.e. poor differentiation, vascular invasion or tumor viability, most centers would use the individual program's routine regimen. There is data favoring the use of mammalian target of rapamycin inhibitors (mTORi) as part of the immunosuppression of any patient transplanted for HCC, however this is not widely accepted practice. In a large study based upon the Scientific Registry of Transplant Recipients, 2,491 patients transplanted for HCC were compared to 12,167 patients transplanted for non-HCC diagnoses. In this study, a multivariate analysis demonstrated improved survivals for patients transplanted for HCC and induced with anti-CD25 antibodies or maintained with a sirolimus-based regimen (Toso, 2010). A more challenging clinical scenario comes up when patients present with high risk tumor features, when the liver explants' pathology reveals a larger tumor burden than anticipated and when the recipient presents with tumor recurrence. The use mTORi and sorafenib has been studied as a potential combination against Ras pathway activation in the genesis of hepatocellular carcinoma (Newell, 2009).The use of Everolimus or Sirolimus in combination with Sorafenib has anecdotally been proven to control HCC recurrence (Wang, 2010; Kim,2011). A close coordination between the transplant and oncology teams should be exercised in this scenario in order to avoid life threatening side effects of the immunosuppressive therapy chosen.
