Probiotic intervention to reduce postoperative inflammation in liver transplantation
Guenther Koellinger1, Miachael Treiber1, Florian Prueller2, Rene Pilz3, Philipp Stiegler1, Robert Sucher1, Peter Schemmer4, Judith Kahn1.
1General, Visceral and Transplant Surgery, Department of Surgery, University Hospital, Medical University of Graz, Graz, Austria; 2Clinical Institute of Medical and Chemical Laboratory Diagnostics, University Hospital, Medical University of Graz, Graz, Austria; 3Department of Psychiatry, Psychosomatics and Psychotherapeutic Medicine , University Hospital, Medical University of Graz, Graz, Austria; 4Bern Visceral Surgery & Pancreas Clinic Switzerland, Hirslanden Hospital Beau-Site, Bern, Switzerland
Introduction: End-stage liver failure as an indication for liver transplantation (LT) and the associated changes in the microbiome can lead to the entry of potentially pathogenic pathogens and their metabolites from the intestine into the bloodstream and thus to pathologically increased inflammation, which can be critical in the context of major surgical procedures such as LT. Associated postoperative infections lead to increased morbidity and mortality, which are also associated with high treatment costs. Prophylactic perioperative pro- and synbiotics are intended to influence the postoperative inflammatory reactions in LT patients.
A meta-analysis of studies on the administration of pro-/synbiotics in LT [1] showed a reduction in postoperative clinical infections with a treatment duration of >10 weeks preoperatively to 14 days postoperatively with a pooled relative risk of 0.24, 95% CI: 0.12– 0.24, and improved postoperative liver function in one of 3 studies.
Method: We performed a randomized, controlled, clinical pilot study including cirrhotic patients listed for LT. 5 patients were randomized in the intervention group with multispecies probiotic for at least 2 months before liver transplantation, 5 patients in the control group without probiotic therapy. Endotoxin concentration and inflammatory markers in peripheral and portal venous blood were measured pre-, peri- and postoperatively, as well as parameters of the intestinal barrier and liver function, clinical outcome, and additional assessment of QoL was performed.
Results: There was no significant difference regarding intestinal translocation based on the measured surrogate parameters cluster of differentiation 14 (CD14) and lipopolysaccharide-binding protein (LBP), as well as the inflammatory and liver function parameters after LT and zonulin as a marker for intestinal barrier function between the two groups. Surgical site infection (SSI) rate was 40% in the control and 20% in the intervention group, duration of antimicrobial therapy after LT was 10 (0-109) days in the intervention group and 20 (0-39) days in the control group. Brief symptom inventory (BSI-18) showed significantly less somatization in the intervention group as compared with the control group.
Conclusion: These results provide important insights for the planning of future clinical trials to investigate the influence of probiotic intervention on the outcome after LT.
1 Kahn J, Pregartner G, Schemmer P. Effects of both Pro- and Synbiotics in Liver Surgery and Transplantation with Special Focus on the Gut-Liver Axis-A Systematic Review and Meta-Analysis. Nutrients. 2020;12(8):2461.
[1] probiotic intervention
[2] liver transplantation
[3] inflammation
[4] infection
[5] QoL