Oncological Impact of M-Tor Inhibitor Immunosuppressive Therapy after Liver Transplantation for Hepatocellular Carcinoma: Review of the Literature

Abstract

Background: Hepatocellular Carcinoma (HCC) represents the fifth most common malignancy and the third cancer-related cause of death worldwide. Hepatitis B (HBV) and C (HCV) viral infections and alcohol abuse are the principal etiological factors for HCC. Liver transplantation (LT) is oncologically the preferable approach to HCC, as it can remove all the intrahepatic tumor foci, and also the oncogenic cirrhotic liver. The use of mTOR inhibitors (mTORi) for immunosuppression after LT for HCC has been proposed due to rapamycin antitumor activity. We decided to review the literature to clarify the oncological role of mTORi after liver transplantation for HCC, analyzing both present condition and future perspectives.Material and Methods: A systematic literature search was performed using PubMed, EMBASE, Scopus, and the Cochrane Library Central. The search was limited to studies in humans and to those reported in the English language in the period of time between January 2005 and December 2015.Results: The literature search yielded 93 articles; after duplicates were removed, 77 titles and abstracts were reviewed. Most relevant data and papers are herein reported and discussed.Conclusions: So far, the use of mTORi is encouraging in terms of oncological outcomes for patients underwent LT for HCC, both for prevention and treatment of HCC recurrence although definitive data are still awaited.

Efficacy and Safety of Everolimus With Reduced Tacrolimus in Liver Transplant Recipients: 24-month Results From the Pooled Analysis of 2 Randomized Controlled Trials

“…In this subanalysis, recurrence of HCC was numerically lower, although not statistically significant, in patients transplanted beyond Milan with EVR + rTAC compared with sTAC (5.9% versus 23.1%, P = 0.215). The results from this subanalysis are in line with the metaanalyses by Cholongitas et al36 and Tarantino et al37 who reported encouraging results with the use of mTORis in terms of prevention and treatment of HCC recurrence in patients undergoing liver transplantation for HCC.…”

No apparent benefit of preemptive sorafenib therapy in liver transplant recipients with advanced hepatocellular carcinoma on explant

“…Use of mTOR inhibitor is encouraging in terms of oncological outcomes for patients undergoing LT for HCC, both for prevention and treatment of HCC recurrence although definitive data are still awaited . Most of the data supporting the potential benefit of mTOR inhibitor were available after 2014, and hence, its use for HCC management was rare prior to this period and their potential benefit is not captured in the current study.…”

“…Use of mTOR inhibitor is encouraging in terms of oncological outcomes for patients undergoing LT for HCC, both for prevention and treatment of HCC recurrence although definitive data are still awaited. 25 Most of the data supporting the potential benefit of mTOR inhibitor were available after 2014, and hence, its use for HCC management was rare prior to this period and their potential benefit is not captured in the current study. Additionally, everolimus was approved by FDA as immunosuppression agent in 2013, and considering patients included in the current study were from 2006 to 2012, everolimus was not used as immunosuppression in these patients prior to their HCC recurrence.…”

Recurrence of Hepatocellular Carcinoma After Liver Transplantation: Risk Factors and Predictive Models

“…Simultaneously, studies have reported encouraging results for anti-cancer treatment with mTOR inhibitors. According to several studies, their use in immunosuppression regimens decreased the risk of recurrence and prolonged survival [ 105 – 109 ]. Publication of the results of a randomized, prospective, multi-center clinical study called the SILVER trial provided a more reliable assessment of the suitability of use of rapamycin derivatives in patients who underwent LTx due to HCC [ 110 ].…”