Value of Probiotics on Outcome in Patients Following Liver Surgery: A Systematic Review and Meta-Analysis

Abstract

Background and Objectives: The gut-liver axis plays a crucial role in the development of post-surgical infections. Surgery-induced dysbiosis can lead to increased bacterial translocation, impairing the liver's detoxification capacity and negatively affecting surgical outcomes. Following liver surgery, approximately a third of the patients develop bacterial infections, with a high risk of bacteremia or even sepsis-related liver failure and death. The potential advantages of administering pro- or synbiotics before/after surgery remain a topic of discussion. Therefore, a systematic review of randomized clinical trials comparing patients with and without supplementation and their outcomes and effects after liver resection (LR) or liver transplantation (LT) was conducted. Materials and Methods: A computer-based search of electronic databases was conducted to gather randomized controlled trials (RCTs) that focused on probiotic/synbiotic use during the perioperative period for liver surgery patients. Two researchers independently screened the studies, extracted the data, evaluated the risk of bias, and performed a meta-analysis using RevMan Web. Results: Our research revealed 19 relevant randomized controlled studies that included a total of 1698 patients on the perioperative use of pro-/symbiotic administration in liver surgery. Eight studies were performed on liver transplantation (LT), and 11 studies were performed for liver resection (LR). The results of the meta-analysis demonstrated that the probiotic group exhibited lower rates of postoperative infectious complications (OR = 0.34; 95%CI 0.25 to 0.45; p < 0.0001), hospital stay duration (SMD = -0.13; 95%CI -0.25 to -0.00; p = 0.05), lower serum endotoxin levels (SMD = -0.39%CI -0.59 to -19; p < 0.0001), and white blood cell counts (SMD = -SMD = -0.35; 95%CI -0.56 to -0.13; p = 0.002) compared to the control group. Further, with regard to liver function, we observed significant postoperative differences in alanine aminotransferase (ALT)-levels (SMD = -0.46; 95%CI -0.63 to -0.29; p < 0.0001), aspartate aminotransferase (AST) levels (SMD = -0.53; 95%CI -0.71 to -0.34; p < 0.0001), bilirubin levels (SMD = -0.35; 95%CI -0.50 to -0.19; p < 0.0001), and international ratio (INR) levels (SMD = -0.1; 95%CI -0.12 to -0.08; p ≤ 0.0001), favoring the symbiotic group compared to the control group. Conclusions: The use of pro-/synbiotics during the perioperative period reduces the risk of postoperative infections, support postoperative liver function, and recovery and shortens hospital stays for liver surgery patients. However, they do not appear to particularly aid in inflammation reduction.

Keywords: hepatectomy; liver resection; liver surgery; liver transplantation; meta-analysis; prebiotics; probiotics; prognosis; randomized controlled trial; synbiotics.

Figure 1

Flow chart of the literature selection.

Figure 2

Risk of bias summary: review of the authors’ judgement on the risk of bias for the analyzed randomized controlled trials.

Figure 3

Forest plot for the meta-analysis of postoperative liver function: (A) alanine aminotransferase (ALT), (B) aspartate aminotransferase (AST), (C) total bilirubin, and (D) international normalized ratio (INR), (+) low risk of bias, (?) unclear risk of bias and (−) high risk of biasl.

Figure 3

Forest plot for the meta-analysis of postoperative liver function: (A) alanine aminotransferase (ALT), (B) aspartate aminotransferase (AST), (C) total bilirubin, and (D) international normalized ratio (INR), (+) low risk of bias, (?) unclear risk of bias and (−) high risk of biasl.

Figure 4

Forest plot for the meta-analysis of postoperative inflammatory indexes: (A) C-reactive protein (CRP); (B) procalcitonin (PCT); (C) white blood cell counts (WBC); (D) endotoxin; (E) interleukin-6, (+) low risk of bias, (?) unclear risk of bias and (−) high risk of bias.

Figure 4

Forest plot for the meta-analysis of postoperative inflammatory indexes: (A) C-reactive protein (CRP); (B) procalcitonin (PCT); (C) white blood cell counts (WBC); (D) endotoxin; (E) interleukin-6, (+) low risk of bias, (?) unclear risk of bias and (−) high risk of bias.

Figure 5

Forest plot for the meta-analysis of postoperative outcome: (A) infection complications in all studies, liver transplantation (C), and liver resection (D); (B) length of hospital stay, (+) low risk of bias, (?) unclear risk of bias and (−) high risk of bias.

Figure 5

Forest plot for the meta-analysis of postoperative outcome: (A) infection complications in all studies, liver transplantation (C), and liver resection (D); (B) length of hospital stay, (+) low risk of bias, (?) unclear risk of bias and (−) high risk of bias.