mTORi‐based immunosuppression reduces HCC recurrence at the expense of increased adverse side effects: A systematic review and meta‐analysis

Sirolimus and everolimus are mammalian target of rapamycin inhibitors (mTORi) that can reduce relapse rates following liver transplantation (LT) for hepatocellular carcinoma (HCC). Herein, we performed a systematic review and meta-analysis to investigate the efficacy of mTORi and calcineurin inhibitors (CNI) in reducing HCC recurrence and survival adverse effects (AEs) in HCC patients after LT. Systematic literature searches were conducted using MEDLINE, EMBASE, and Cochrane Library databases up to October 2021. The primary outcomes of interest were tumor recurrence rates and overall survival. The secondary outcomes were the characterization and incidence of AEs. A total of 38 trials involving 10,607 participants was included in the analysis. The incidence of recurrence and overall mortality was significantly lower in the mTORi than in the CNI group (relative ratio [RR]: .78, 95% confidence interval [CI]: .68-.89 and RR: .76, 95% CI: .67-.86, respectively). The incidence of some AEs and complications such as acne, anemia, abnormal healing, dyslipidemia, depression, diarrhea, edema, headache/migraine, hypercholesterolemia, incisional hernia, infection, leukopenia, mouth ulceration, pyrexia, proteinuria, pruritis, rash, and thrombocytopenia were higher in the mTORi than in the CNI group. mTORi reduced the recurrence incidence and overall 5-year mortality rate but increased many other incidences of AEs compared with that by CNI. Therefore, clinicians should be aware of the risks and benefits of mTORi use when managing patients undergoing LT for HCC.