title: Mammalian target of rapamycin inhibitors are associated with lower rates of hepatocellular carcinoma recurrence after liver transplantation: a systematic review.
abstract: Calcineurin inhibitors (CNIs) have been associated in a dose-dependent fashion with an increased risk of post-transplant hepatocellular carcinoma (HCC) recurrence. The mammalian target of rapamycin inhibitors (mTORi) (sirolimus/everolimus) might represent an alternative immunosuppressive regimen with antineoplastic effect. In the present systematic review, the association between mTORi and HCC recurrence after liver transplantation (LT) was evaluated and compared against that of CNIs-treated patients. In total, 3666 HCC liver transplant recipients from 42 studies met the inclusion criteria. Patients under CNIs developed HCC recurrence significantly more frequently, compared with patients under mTORi (448/3227 or 13.8% vs. 35/439 or 8%, P < 0.001), although patients treated with CNIs had a higher proportion of HCC within Milan criteria (74% vs. 69%) and lower rates of microvascular invasion, compared with mTORi-treated patients (22% vs. 44%) (P < 0.05). Patients on everolimus had significantly lower recurrence rates of HCC, compared with those on sirolimus or CNIs (4.1% vs. 10.5% vs. 13.8%, respectively, P < 0.05), but everolimus-treated recipients had shorter follow-up period (13 vs. 30 vs. 43.2 months, respectively) and more frequently been transplanted for HCC within Milan criteria (84% vs. 60.5% vs. 74%, respectively, P < 0.05). Our findings favor the use of mTORi instead of CNIs to control HCC recurrence after LT, but comparative studies with longer follow-up are needed for final conclusions.
authors.affiliation: 4th Department of Internal Medicine, Medical School of Aristotle University, Hippokration General Hospital of Thessaloniki, Thessaloniki, Greece.
authors.forename: Evangelos
authors.initials: E
authors.lastname: Cholongitas
authors.forename: Chrysanthi
authors.initials: C
authors.lastname: Mamou
authors.forename: Kryssia I
authors.initials: KI
authors.lastname: Rodríguez-Castro
authors.forename: Patrizia
authors.initials: P
authors.lastname: Burra
mesh_terms: D065095:Calcineurin Inhibitors / Q000008:administration & dosage; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000601:surgery; D015331:Cohort Studies; D016503:Drug Delivery Systems; D000068338:Everolimus; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D015994:Incidence; D008113:Liver Neoplasms / Q000473:pathology / Q000601:surgery; D016031:Liver Transplantation / Q000009:adverse effects / Q000379:methods*; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000453:epidemiology / Q000517:prevention & control*; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D020123:Sirolimus / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D016896:Treatment Outcome
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D000068338:Everolimus; D020123:Sirolimus
keywords: cyclosporine; everolimus; hepatocellular carcinoma recurrence; immunosuppression; liver transplantation; sirolimus; tacrolimus