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26.11.2021 | Original Scientific Report

Influence of Probiotics Administration Before Liver Resection in Patients with Liver Disease: A Randomized Controlled Trial

verfasst von: Edouard Roussel, Carole Brasse-Lagnel, Jean-Jacques Tuech, Helène Montialoux, Eloise Papet, Pauline Tortajada, Soumeya Bekri, Lilian Schwarz

Erschienen in: World Journal of Surgery | Ausgabe 3/2022

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Abstract

Background

By inhibiting the growth of pathogenic bacteria and modulating the local intestinal immune system, probiotics may reduce bacterial translocation and systemic endotoxaemia, factors partially responsible for post-operative complications following liver resection for hepatocellular carcinoma in patients with cirrhosis.

Methods

Patients with resectable hepatocellular carcinoma developed in the setting of chronic liver disease were prospectively divided into two equal-sized groups: one receiving probiotic treatment 14 days prior to surgery and the other receiving placebo. The primary endpoint was the level of circulating endotoxins after hepatectomy. Secondary endpoints were systemic inflammation (inflammatory cytokine levels), post-operative liver function and overall post-operative complication rate.

Results

From May 2013 to December 2018, 64 patients were randomized, and 54 patients were included in the analysis, 27 in each arm. No significant change in endotoxin levels was observed over time in either group (P = 0.299). No difference between the groups in terms of post-operative liver function and overall complication rates was observed. The only differences observed were significant increases in the levels of TNFalpha (P = 0.019) and interleukin 1-b (P = 0.028) in the probiotic group in the post-operative period.

Conclusion

Contrary to the modest data reported in the literature, the administration of probiotics before minor liver resection for hepatocellular carcinoma developed in the setting of compensated chronic liver disease does not seem to have an impact on circulating endotoxin levels or post-operative complication rates.

Trial registration

Trial registration: NCT02021253.
Literatur
1.
Zurück zum Zitat Filmann N, Walter D, Schadde E et al (2019) Mortality after liver surgery in Germany. Br J Surg 106(11):1523–1529PubMedCrossRef Filmann N, Walter D, Schadde E et al (2019) Mortality after liver surgery in Germany. Br J Surg 106(11):1523–1529PubMedCrossRef
2.
Zurück zum Zitat Cirera I, Bauer TM, Navasa M et al (2001) Bacterial translocation of enteric organisms in patients with cirrhosis. J Hepatol 34:32PubMedCrossRef Cirera I, Bauer TM, Navasa M et al (2001) Bacterial translocation of enteric organisms in patients with cirrhosis. J Hepatol 34:32PubMedCrossRef
3.
Zurück zum Zitat Yeh D-C, Wu C-C, Ho W-M et al (2003) Bacterial translocation after cirrhotic liver resection: a clinical investigation of 181 patients. J Surg Res 111(2):209–214PubMedCrossRef Yeh D-C, Wu C-C, Ho W-M et al (2003) Bacterial translocation after cirrhotic liver resection: a clinical investigation of 181 patients. J Surg Res 111(2):209–214PubMedCrossRef
5.
Zurück zum Zitat Stoclet JC, Fleming I, Gray G et al (1993) Nitric oxide and endotoxemia. Circulation 87(SUPPL V):V77–V80 Stoclet JC, Fleming I, Gray G et al (1993) Nitric oxide and endotoxemia. Circulation 87(SUPPL V):V77–V80
6.
Zurück zum Zitat Sogni P, Moreau R, Lebrec D (1999) Endotoxemia: an unnecessary but aggravating condition in portal hypertension? J Hepatol 30(6):1160–1162PubMedCrossRef Sogni P, Moreau R, Lebrec D (1999) Endotoxemia: an unnecessary but aggravating condition in portal hypertension? J Hepatol 30(6):1160–1162PubMedCrossRef
7.
Zurück zum Zitat Lin CY, Tsai IF, Ho YP et al (2007) Endotoxemia contributes to the immune paralysis in patients with cirrhosis. J Hepatol 46(5):816–826PubMedCrossRef Lin CY, Tsai IF, Ho YP et al (2007) Endotoxemia contributes to the immune paralysis in patients with cirrhosis. J Hepatol 46(5):816–826PubMedCrossRef
8.
Zurück zum Zitat Stadlbauer V, Davies NA, Wright GA et al (2007) Endotoxemia during liver transplantation. Liver Transpl 13(11):1616–1617PubMedCrossRef Stadlbauer V, Davies NA, Wright GA et al (2007) Endotoxemia during liver transplantation. Liver Transpl 13(11):1616–1617PubMedCrossRef
9.
Zurück zum Zitat Nakagawa K, Matsubara S, Ouchi K, Owada Y, Yajima Y (1986) Endotoxemia after abdominal surgery. Tohoku J Exp Med 150(3):273–280PubMedCrossRef Nakagawa K, Matsubara S, Ouchi K, Owada Y, Yajima Y (1986) Endotoxemia after abdominal surgery. Tohoku J Exp Med 150(3):273–280PubMedCrossRef
10.
Zurück zum Zitat Nakagawa K, Ouchi K, Matsubara S et al (1987) Activation of reticuloendothelial function for prevention of endotoxemia after hepatectomy in cirrhotic patients. Tohoku J Exp Med 153(2):133–136PubMedCrossRef Nakagawa K, Ouchi K, Matsubara S et al (1987) Activation of reticuloendothelial function for prevention of endotoxemia after hepatectomy in cirrhotic patients. Tohoku J Exp Med 153(2):133–136PubMedCrossRef
11.
Zurück zum Zitat Nolan JP (2010) The role of intestinal endotoxin in liver injury: a long and evolving history. Hepatology 52(5):1829–1835PubMedCrossRef Nolan JP (2010) The role of intestinal endotoxin in liver injury: a long and evolving history. Hepatology 52(5):1829–1835PubMedCrossRef
12.
Zurück zum Zitat Qin N, Yang F, Li A et al (2014) Alterations of the human gut microbiome in liver cirrhosis. Nature 513(7516):59–64PubMedCrossRef Qin N, Yang F, Li A et al (2014) Alterations of the human gut microbiome in liver cirrhosis. Nature 513(7516):59–64PubMedCrossRef
13.
Zurück zum Zitat Chen Y, Yang F, Lu H et al (2011) Characterization of fecal microbial communities in patients with liver cirrhosis. Hepatology 54(2):562–572PubMedCrossRef Chen Y, Yang F, Lu H et al (2011) Characterization of fecal microbial communities in patients with liver cirrhosis. Hepatology 54(2):562–572PubMedCrossRef
14.
Zurück zum Zitat Hill C, Guarner F, Reid G et al (2014) The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol 11(8):506–514PubMedCrossRef Hill C, Guarner F, Reid G et al (2014) The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol 11(8):506–514PubMedCrossRef
15.
Zurück zum Zitat Bongaerts GPA, Severijnen RSVM (2016) A reassessment of the PROPATRIA study and its implications for probiotic therapy. Nat Biotechnol 34(1):55–63PubMedCrossRef Bongaerts GPA, Severijnen RSVM (2016) A reassessment of the PROPATRIA study and its implications for probiotic therapy. Nat Biotechnol 34(1):55–63PubMedCrossRef
16.
Zurück zum Zitat Saab S, Suraweera D, Au J, Saab EG, Alper TS, Tong MJ (2016) Probiotics are helpful in hepatic encephalopathy: a meta-analysis of randomized trials. Liver Int 36(7):986–993PubMedCrossRef Saab S, Suraweera D, Au J, Saab EG, Alper TS, Tong MJ (2016) Probiotics are helpful in hepatic encephalopathy: a meta-analysis of randomized trials. Liver Int 36(7):986–993PubMedCrossRef
17.
Zurück zum Zitat Dhiman RK, Rana B, Agrawal S et al (2014) Probiotic VSL#3 reduces liver disease severity and hospitalization in patients with cirrhosis: a randomized, controlled trial. Gastroenterology 147(6):1327-1337.e3PubMedCrossRef Dhiman RK, Rana B, Agrawal S et al (2014) Probiotic VSL#3 reduces liver disease severity and hospitalization in patients with cirrhosis: a randomized, controlled trial. Gastroenterology 147(6):1327-1337.e3PubMedCrossRef
18.
Zurück zum Zitat Bajaj JS, Heuman DM, Hylemon PB et al (2014) Randomised clinical trial: Lactobacillus GG modulates gut microbiome, metabolome and endotoxemia in patients with cirrhosis. Aliment Pharmacol Ther 39(10):1113–1125PubMedPubMedCentralCrossRef Bajaj JS, Heuman DM, Hylemon PB et al (2014) Randomised clinical trial: Lactobacillus GG modulates gut microbiome, metabolome and endotoxemia in patients with cirrhosis. Aliment Pharmacol Ther 39(10):1113–1125PubMedPubMedCentralCrossRef
19.
Zurück zum Zitat Rayes N, Pilarski T, Stockmann M, Bengmark S, Neuhaus P, Seehofer D (2012) Effect of pre- and probiotics on liver regeneration after resection: a randomised, double-blind pilot study. Benef Microbes 3(3):237–244PubMedCrossRef Rayes N, Pilarski T, Stockmann M, Bengmark S, Neuhaus P, Seehofer D (2012) Effect of pre- and probiotics on liver regeneration after resection: a randomised, double-blind pilot study. Benef Microbes 3(3):237–244PubMedCrossRef
20.
Zurück zum Zitat Iida H, Sasaki M, Maehira H et al (2020) The effect of preoperative synbiotic treatment to prevent surgical-site infection in hepatic resection. J Clin Biochem Nutr 66(1):67–73PubMedCrossRef Iida H, Sasaki M, Maehira H et al (2020) The effect of preoperative synbiotic treatment to prevent surgical-site infection in hepatic resection. J Clin Biochem Nutr 66(1):67–73PubMedCrossRef
21.
Zurück zum Zitat Grąt M, Wronka KM, Lewandowski Z et al (2017) Effects of continuous use of probiotics before liver transplantation: a randomized, double-blind, placebo-controlled trial. Clin Nutr 36(6):1530–1539PubMedCrossRef Grąt M, Wronka KM, Lewandowski Z et al (2017) Effects of continuous use of probiotics before liver transplantation: a randomized, double-blind, placebo-controlled trial. Clin Nutr 36(6):1530–1539PubMedCrossRef
22.
Zurück zum Zitat Ray S, Mehta NN, Golhar A, Nundy S (2018) Post hepatectomy liver failure—a comprehensive review of current concepts and controversies. Ann Med Surg (Lond) 34:4–10CrossRef Ray S, Mehta NN, Golhar A, Nundy S (2018) Post hepatectomy liver failure—a comprehensive review of current concepts and controversies. Ann Med Surg (Lond) 34:4–10CrossRef
23.
Zurück zum Zitat Trebicka J, Krag A, Gansweid S et al (2011) Endotoxin and tumor necrosis factor-receptor levels in portal and hepatic vein of patients with alcoholic liver cirrhosis receiving elective transjugular intrahepatic portosystemic shunt. Eur J Gastroenterol Hepatol 23(12):1218–1225PubMedCrossRef Trebicka J, Krag A, Gansweid S et al (2011) Endotoxin and tumor necrosis factor-receptor levels in portal and hepatic vein of patients with alcoholic liver cirrhosis receiving elective transjugular intrahepatic portosystemic shunt. Eur J Gastroenterol Hepatol 23(12):1218–1225PubMedCrossRef
24.
Zurück zum Zitat Sugawara G, Nagino M, Nishio H et al (2006) Perioperative synbiotic treatment to prevent postoperative infectious complications in biliary cancer surgery: a randomized controlled trial. Ann Surg 244(5):706–714PubMedPubMedCentralCrossRef Sugawara G, Nagino M, Nishio H et al (2006) Perioperative synbiotic treatment to prevent postoperative infectious complications in biliary cancer surgery: a randomized controlled trial. Ann Surg 244(5):706–714PubMedPubMedCentralCrossRef
25.
Zurück zum Zitat Rayes N, Seehofer D, Theruvath T et al (2005) Supply of pre- and probiotics reduces bacterial infection rates after liver transplantation-a randomized, Double-Blind Trial. Am J Transplant 5(1):125–130PubMedCrossRef Rayes N, Seehofer D, Theruvath T et al (2005) Supply of pre- and probiotics reduces bacterial infection rates after liver transplantation-a randomized, Double-Blind Trial. Am J Transplant 5(1):125–130PubMedCrossRef
26.
Zurück zum Zitat Coltart I, Tranah TH, Shawcross DL (2013) Inflammation and hepatic encephalopathy. Arch Biochem Biophys 536(2):189–196PubMedCrossRef Coltart I, Tranah TH, Shawcross DL (2013) Inflammation and hepatic encephalopathy. Arch Biochem Biophys 536(2):189–196PubMedCrossRef
27.
Zurück zum Zitat Violi F, Ferro D, Basili S et al (1995) Association between low-grade disseminated intravascular coagulation and endotoxemia in patients with liver cirrhosis. Gastroenterology 109(2):531–539PubMedCrossRef Violi F, Ferro D, Basili S et al (1995) Association between low-grade disseminated intravascular coagulation and endotoxemia in patients with liver cirrhosis. Gastroenterology 109(2):531–539PubMedCrossRef
28.
Zurück zum Zitat Lata J, Novotný I, Příbramská V et al (2007) The effect of probiotics on gut flora, level of endotoxin and Child-Pugh score in cirrhotic patients: results of a double-blind randomized study. Eur J Gastroenterol Hepatol 19(12):1111–1113PubMedCrossRef Lata J, Novotný I, Příbramská V et al (2007) The effect of probiotics on gut flora, level of endotoxin and Child-Pugh score in cirrhotic patients: results of a double-blind randomized study. Eur J Gastroenterol Hepatol 19(12):1111–1113PubMedCrossRef
29.
Zurück zum Zitat Chu CJ, Lee FY, Wang SS et al (1997) Hyperdynamic circulation of cirrhotic rats with ascites: role of endotoxin, tumour necrosis factor-alpha and nitric oxide. Clin Sci 93(3):219–225CrossRef Chu CJ, Lee FY, Wang SS et al (1997) Hyperdynamic circulation of cirrhotic rats with ascites: role of endotoxin, tumour necrosis factor-alpha and nitric oxide. Clin Sci 93(3):219–225CrossRef
30.
Zurück zum Zitat Guarner C, Soriano G, Tomas A et al (1993) Increased serum nitrite and nitrate levels in patients with cirrhosis: relationship to endotoxemia. Hepatology 18(5):1139–1143PubMedCrossRef Guarner C, Soriano G, Tomas A et al (1993) Increased serum nitrite and nitrate levels in patients with cirrhosis: relationship to endotoxemia. Hepatology 18(5):1139–1143PubMedCrossRef
31.
32.
Zurück zum Zitat Draisma A, Pickkers P, Bouw MPWJM, van der Hoeven JG (2009) Development of endotoxin tolerance in humans in vivo. Crit Care Med 37(4):1261–1267PubMedCrossRef Draisma A, Pickkers P, Bouw MPWJM, van der Hoeven JG (2009) Development of endotoxin tolerance in humans in vivo. Crit Care Med 37(4):1261–1267PubMedCrossRef
33.
Zurück zum Zitat Liu Z, Li C, Huang M et al (2015) Positive regulatory effects of perioperative probiotic treatment on postoperative liver complications after colorectal liver metastases surgery: a double-center and double-blind randomized clinical trial. BMC Gastroenterol 15(1):34PubMedPubMedCentralCrossRef Liu Z, Li C, Huang M et al (2015) Positive regulatory effects of perioperative probiotic treatment on postoperative liver complications after colorectal liver metastases surgery: a double-center and double-blind randomized clinical trial. BMC Gastroenterol 15(1):34PubMedPubMedCentralCrossRef
34.
Zurück zum Zitat Melloul E, Hübner M, Scott M et al (2016) Guidelines for perioperative care for liver surgery: enhanced recovery after surgery (ERAS) Society Recommendations. World J Surg 40(10):2425–2440PubMedCrossRef Melloul E, Hübner M, Scott M et al (2016) Guidelines for perioperative care for liver surgery: enhanced recovery after surgery (ERAS) Society Recommendations. World J Surg 40(10):2425–2440PubMedCrossRef
35.
Zurück zum Zitat Kanazawa H, Nagino M, Kamiya S et al (2005) Synbiotics reduce postoperative infectious complications: a randomized controlled trial in biliary cancer patients undergoing hepatectomy. Langenbecks Arch Surg 390(2):104–113PubMedCrossRef Kanazawa H, Nagino M, Kamiya S et al (2005) Synbiotics reduce postoperative infectious complications: a randomized controlled trial in biliary cancer patients undergoing hepatectomy. Langenbecks Arch Surg 390(2):104–113PubMedCrossRef
36.
Zurück zum Zitat Eguchi S, Takatsuki M, Hidaka M, Soyama A, Ichikawa T, Kanematsu T (2011) Perioperative synbiotic treatment to prevent infectious complications in patients after elective living donor liver transplantation: a prospective randomized study. Am J Surg 201(4):498–502PubMedCrossRef Eguchi S, Takatsuki M, Hidaka M, Soyama A, Ichikawa T, Kanematsu T (2011) Perioperative synbiotic treatment to prevent infectious complications in patients after elective living donor liver transplantation: a prospective randomized study. Am J Surg 201(4):498–502PubMedCrossRef
37.
Zurück zum Zitat Wu X-D, Liu M-M, Liang X, Hu N, Huang W (2018) Effects of perioperative supplementation with pro-/synbiotics on clinical outcomes in surgical patients: a meta-analysis with trial sequential analysis of randomized controlled trials. Clin Nutr 37(2):505–515PubMedCrossRef Wu X-D, Liu M-M, Liang X, Hu N, Huang W (2018) Effects of perioperative supplementation with pro-/synbiotics on clinical outcomes in surgical patients: a meta-analysis with trial sequential analysis of randomized controlled trials. Clin Nutr 37(2):505–515PubMedCrossRef
38.
Zurück zum Zitat Chowdhury AH, Adiamah A, Kushairi A et al (2019) Perioperative probiotics or synbiotics in adults undergoing elective abdominal surgery: a systematic review and meta-analysis of randomized controlled trials. Ann Surg 31:112 Chowdhury AH, Adiamah A, Kushairi A et al (2019) Perioperative probiotics or synbiotics in adults undergoing elective abdominal surgery: a systematic review and meta-analysis of randomized controlled trials. Ann Surg 31:112
39.
Zurück zum Zitat Pereg D, Kotliroff A, Gadoth N, Hadary R, Lishner M, Kitay-Cohen Y (2011) Probiotics for patients with compensated liver cirrhosis: a double-blind placebo-controlled study. Nutrition 27(2):177–181PubMedCrossRef Pereg D, Kotliroff A, Gadoth N, Hadary R, Lishner M, Kitay-Cohen Y (2011) Probiotics for patients with compensated liver cirrhosis: a double-blind placebo-controlled study. Nutrition 27(2):177–181PubMedCrossRef
40.
Zurück zum Zitat Horvath A, Leber B, Schmerboeck B et al (2016) Randomised clinical trial: the effects of a multispecies probiotic vs. placebo on innate immune function, bacterial translocation and gut permeability in patients with cirrhosis. Aliment Pharmacol Ther 44(9):926–935PubMedPubMedCentralCrossRef Horvath A, Leber B, Schmerboeck B et al (2016) Randomised clinical trial: the effects of a multispecies probiotic vs. placebo on innate immune function, bacterial translocation and gut permeability in patients with cirrhosis. Aliment Pharmacol Ther 44(9):926–935PubMedPubMedCentralCrossRef
41.
Zurück zum Zitat Zmora N, Zilberman-Schapira G, Suez J et al (2018) Personalized gut mucosal colonization resistance to empiric probiotics is associated with unique host and microbiome features. Cell 174(6):1388-1405.e21PubMedCrossRef Zmora N, Zilberman-Schapira G, Suez J et al (2018) Personalized gut mucosal colonization resistance to empiric probiotics is associated with unique host and microbiome features. Cell 174(6):1388-1405.e21PubMedCrossRef
42.
Zurück zum Zitat Schwenger KJ, Clermont-Dejean N, Allard JP (2019) The role of the gut microbiome in chronic liver disease: the clinical evidence revised. JHEP Rep 1(3):214–226PubMedPubMedCentralCrossRef Schwenger KJ, Clermont-Dejean N, Allard JP (2019) The role of the gut microbiome in chronic liver disease: the clinical evidence revised. JHEP Rep 1(3):214–226PubMedPubMedCentralCrossRef
43.
Zurück zum Zitat Bauer TM, Fernández J, Navasa M, Vila J, Rodés J (2002) Failure of Lactobacillus spp. to prevent bacterial translocation in a rat model of experimental cirrhosis. J Hepatol 36(4):501–506PubMedCrossRef Bauer TM, Fernández J, Navasa M, Vila J, Rodés J (2002) Failure of Lactobacillus spp. to prevent bacterial translocation in a rat model of experimental cirrhosis. J Hepatol 36(4):501–506PubMedCrossRef
44.
Zurück zum Zitat Gnauck A, Lentle RG, Kruger MC (2016) Chasing a ghost? Issues with the determination of circulating levels of endotoxin in human blood. Crit Rev Clin Lab Sci 53(3):197–215PubMedCrossRef Gnauck A, Lentle RG, Kruger MC (2016) Chasing a ghost? Issues with the determination of circulating levels of endotoxin in human blood. Crit Rev Clin Lab Sci 53(3):197–215PubMedCrossRef
Metadaten
Titel
Influence of Probiotics Administration Before Liver Resection in Patients with Liver Disease: A Randomized Controlled Trial
verfasst von
Edouard Roussel
Carole Brasse-Lagnel
Jean-Jacques Tuech
Helène Montialoux
Eloise Papet
Pauline Tortajada
Soumeya Bekri
Lilian Schwarz
Publikationsdatum
26.11.2021
Verlag
Springer International Publishing
Erschienen in
World Journal of Surgery / Ausgabe 3/2022
Print ISSN: 0364-2313
Elektronische ISSN: 1432-2323
DOI
https://doi.org/10.1007/s00268-021-06388-7

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