Sirolimus or Everolimus Improves Survival After Liver Transplantation for Hepatocellular Carcinoma: A Systematic Review and Meta‐Analysis

Abstract

The effects of mammalian target of rapamycin (mTOR) inhibitors (sirolimus [SRL] and everolimus [EVL]) on survival in liver transplantation (LT) recipients with hepatocellular carcinoma (HCC) remain the subject of intense research. Therefore, we performed this systematic review and meta-analysis to investigate the potential survival benefits of mTOR inhibitors (mTORis). Embase, PubMed, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for all randomized controlled trials (RCTs) and cohort studies investigating effects of SRL or EVL on LT recipients for HCC. The primary outcomes were 1-, 2-, 3-, and 5-year overall survival (OS), and the secondary outcomes were 1-, 2-, and 3-year recurrence-free survival (RFS) and adverse effects. Pooled relative risks (RRs) with 95% confidence interval (CI) were calculated by a fixed or random effects model with Mantel-Haenszel weighting. Subgroup analyses were performed according to crucial clinical characteristics. We also conducted sensitivity analyses to assess the reliability of our findings. A total of 17 studies were included. OS was improved in both RCTs (1 year: RR,

2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma

“…[468][469][470] Recent meta-analysis reported better outcomes in mTORi group than non-mTORi groups in the 5-year RFS rate (ratio, 1.13; 95% CI, 1.02-1.26 in RCT and ratio, 1.17; 95 CI, 1.10-1.24 in cohort study). 471 Therefore, if there are no significant adverse events related to drugs, mTORi may be considered in LT recipients with HCC.…”

“…Recent studies have shown that the use of mTORi may be helpful for reducing recurrence and prolonging survival in HCC patients after LT, but further studies are needed [ 468 - 470 ]. Recent meta-analysis reported better outcomes in mTORi group than non-mTORi groups in the 5-year RFS rate (ratio, 1.13; 95% CI, 1.02–1.26 in RCT and ratio, 1.17; 95 CI, 1.10–1.24 in cohort study) [ 471 ]. Therefore, if there are no significant adverse events related to drugs, mTORi may be considered in LT recipients with HCC.…”

Sirolimus vs tacrolimus: Which one is the best therapeutic option for patients undergoing liver transplantation for hepatocellular carcinoma?

“…The most important indication for LT is concurrent HCC and cirrhosis. For end-stage liver diseases, LT is the most effective strategy[ 7 ]. However, tumor recurrence remains a significant challenge.…”

“…A systematic review and meta-analysis reported that SRL or EVL improved one, two, three and five-year overall survival (OS) [randomised controlled trials: 1-year, relative risk (RR) =1.04, 95%CI: 1.00-1.08; 2-year, RR = 1.09, 95%CI: 1.02-1.16; 3-year, RR = 1.13, 95%CI: 1.04-1.24; 5-year, RR = 1.13, 95%CI: 1.02-1.26) vs (cohort studies: 1-year, RR = 1.13, 95%CI: 1.06-1.20; 2-year, RR = 1.24, 95%CI: 1.16-1.32; 3-year, RR = 1.24, 95%CI: 1.15-1.34; 5-year, RR = 1.17, 95%CI: 1.10-1.24)), respectively[ 7 ]. A 13% improvement in OS was demonstrated over five years, with 14% survival benefit in three years, and minimal risk of nephrotoxicity was noticed (RR = 0.75, 95%CI: 0.60-0.93) in the mTOR inhibitors group.…”

Mammalian Target of Rapamycin and Hepatocellular Carcinoma: The Question's Always There, Until We Choose To Answer It

“…In this issue of Liver Transplantation , Yan et al ( 1 ) synthesize existing data through a systematic review and meta‐analysis to attempt to answer whether mammalian target of rapamycin (mTOR) immunosuppression protocols influence hepatocellular carcinoma (HCC) recurrence. This study updates prior meta‐analyses on the subject, which primarily included a limited number of observational studies.…”