Efficacy and safety of different options for liver regeneration of future liver remnant in patients with liver malignancies: a systematic review and network meta-analysis

Background: Several treatments induce liver hypertrophy for patients with liver malignancies but insufficient future liver remnant (FLR). Herein, the aim of this study is to compare the efficacy and safety of existing surgical techniques using network meta-analysis (NMA). Methods: We searched PubMed, Web of Science, and Cochrane Library from databases for abstracts and full-text articles published from database inception through Feb 2022. The primary outcome was the efficacy of different procedures, including standardized FLR (sFLR) increase, time to hepatectomy, resection rate, and R0 resection margin. The secondary outcome was the safety of different treatments, including the rate of Clavien-Dindo & GE;3a and 90-day mortality. Results: Twenty-seven studies, including three randomized controlled trials (RCTs), three prospective trials (PTs), and twenty-one retrospective trials (RTs), and a total number of 2075 patients were recruited in this study. NMA demonstrated that the Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) had much higher sFLR increase when compared to portal vein embolization (PVE) (55.25%, 95% CI 45.27-65.24%), or liver venous deprivation(LVD) (43.26%, 95% CI 22.05-64.47%), or two-stage hepatectomy (TSH) (30.53%, 95% CI 16.84-44.21%), or portal vein ligation (PVL) (58.42%, 95% CI 37.62-79.23%). ALPPS showed significantly shorter time to hepatectomy when compared to PVE (-32.79d, 95% CI -42.92-22.66), or LVD (-34.02d, 95% CI -47.85-20.20), or TSH (-22.85d, 95% CI -30.97-14.72), or PVL (-43.37d, 95% CI -64.11-22.62); ALPPS was considered as the highest resection rate when compared to TSH (OR=6.09; 95% CI 2.76-13.41), or PVL (OR =3.52; 95% CI 1.16-10.72), or PVE (OR =4.12; 95% CI 2.19-7.77). ALPPS had comparable resection rate with LVD (OR =2.20; 95% CI 0.83-5.86). There was no significant difference between them when considering the R0 marge rate. ALPPS had a higher Clavien-Dindo & GE;3a complication rate and 90-day mortality compared to other treatments, although there were no significant differences between different procedures. Conclusions: ALPPS demonstrated a higher regeneration rate, shorter time to hepatectomy, and higher resection rate than PVL, PVE, or TSH. There was no significant difference between them when considering the R0 marge rate. However, ALPPS developed the trend of higher Clavien-Dindo & GE;3a complication rate and 90-day mortality compared to other treatments.