The Role of mTOR Inhibitors after Liver Transplantation for Hepatocellular Carcinoma

Abstract

Liver transplantation is a treatment option for nonresectable patients with early-stage HCC, with more significant advantages when Milan criteria are fulfilled. An immunosuppressive regimen is required to reduce the risk of graft rejection after transplantation, and CNIs represent the drugs of choice in this setting. However, their inhibitory effect on T-cell activity accounts for a higher risk of tumour regrowth. mTOR inhibitors (mTORi) have been introduced as an alternative immunosuppressive approach to conventional CNI-based regimens to address both immunosuppression and cancer control. The PI3K-AKT-mTOR signalling pathway regulates protein translation, cell growth, and metabolism, and the pathway is frequently deregulated in human tumours. Several studies have suggested the role of mTORi in reducing HCC progression after LT, accounting for a lower recurrence rate. Furthermore, mTOR immunosuppression controls the renal damage associated with CNI exposure. Conversion to mTOR inhibitors is associated with stabilizing and recovering renal dysfunction, suggesting an essential renoprotective effect. Limitations in this therapeutic approach are related to their negative impact on lipid and glucose metabolism as well as on proteinuria development and wound healing. This review aims to summarize the roles of mTORi in managing patients with HCC undergoing LT. Strategies to overcome common adverse effects are also proposed.

Keywords

• hepatocellular carcinoma
• HCC
• immunosuppression
• liver transplantation
• mTOR
• mTOR inhibitors