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THE ROLE OF THE GUT-LIVER AXIS IN LIVER CIRRHOSIS PATHOGENESIS AND COMPLICATIONS

Keywords: Liver, intestines, permeability, bacterial translocation

Abstract

Background. Liver cirrhosis is a severe disease that can provoke hepatocellular carcinoma. It is known that such patients have increased intestinal permeability causing the translocation of living bacteria and bacterial products through the inferior vena cava system into the liver, that leads to a cascade of immune and molecular events. Objective – to establish the role of the gut-liver axis in the pathogenesis and outcomes of liver cirrhosis. Material and methods. We performed a PubMed search of publications over the last 10 years, using the keywords ‘intestinal permeability’, ‘cirrhosis’. Results. Increased intestinal permeability and bacterial translocation are of great importance in the development of liver cirrhosis. In turn, the progression of the disease further enhances the transfer of bacteria from the intestine into the inferior vena cava system. The severity of this process is proportional to the stage of cirrhosis and correlates with the prognosis of the disease. Conclusion. Increased intestinal permeability, altered gut microbiota and bacterial translocation contribute to liver damage and fibrosis up to the development of liver cirrhosis and its complications. Further research is required to determine if modulation of the gut microbiota can affect the course of liver disease.

References

Brandl K, Kumar V, Eckmann L. Gut-liver axis at the frontier of host-microbial interactions. Am. J. Physiol. Gastrointest. Liver Physiol. 2017;312(5):413-419. https://doi.org/10.1152/ajpgi.00361.2016.

Wiest R, Lawson M, Geuking M. Pathological bacterial translocation in liver cirrhosis. J. Hepatol. 2014;60(1):197-209. https://doi.org/10.1016/j.jhep.2013.07.044.

Reiberger T, Ferlitsch A, Payer BA, Mandorfer M, Heinisch BB, Hayden H, Lammert F, Trauner M, Peck-Radosav M, Vogelsang H. Non-selective betablocker therapy decreases intestinal permeability and serum levels of LBP and IL-6 in patients with cirrhosis. J. Hepatol. 2013;58(5):911-921. https://doi.org/10.1016/j.jhep.2012.12.011.

Baffy G. Potential mechanisms linking gut microbiota and portal hypertension. Liver Int. 2019;39(4):598-609. https://doi.org/10.1111/liv.13986.

McAvoy NC, Semple S, Richards JMJ, Robson AJ, Patel D, Jardine AGM, Leyland K, Cooper AS, Newby DE, Hayes PC. Differential visceral blood flow in the hyperdynamic circulation of patients with liver cirrhosis. Aliment Pharmacol Ther. 2016;43(9):947-954. https://doi.org/10.1111/apt.13571.

Du Plessis J, Vanheel H, Janssen CEI, Roos L, Slavik T, Stivaktas PI, Nieuwoudt M, van Wyk SG, Vieira W, Pretoriuse E, Beukes M, Farre R, Nack J, Laleman W, Fevery J, Nevens F, Roskams T, van der Merwe S. Activated intestinal macrophages in patients with cirrhosis release NO and IL-6 that may disrupt intestinal barrier function. J. Hepatol. 2013;58(6):1125-1132. https://doi.org/10.1016/j.jhep.2013.01.038.

Zhu Q, Zou L, Jagavelu R, Simonetto DA, Huebert RC, Zhi-Dong J, DuPont HL, Vijay H. Shah Intestinal decontamination inhibits TLR4 dependent fibronectin-mediated cross-talk between stellate cells and endothelial cells in liver fibrosis in mice.J. Hepatol. 2012;56(4):893-899. https://doi.org/10.1016/j.jhep.2011.11.013.

Lin RS, Lee FY, Lee SD, Tsai IT, Lin CH, Lu RH, Hsu WC, Huang CC, Wang SS, Lo KJ. Endotoxemia in patients with chronic liver diseases: relationship to severity of liver diseases, presence of esophageal varices, and hyperdynamic circulation. J. Hepatol. 2015;22(2):165-172. https://doi.org/10.1016/0168-8278(95)80424-2.

Mindikoglu AY, Pappas SC. New developments in hepatorenal syndrome. Clin. Gastroentrerol. Heratol. 2018;16(2):162-177.

Huang L, Hung J, Chen C, Hsieh C, Yu H, Hsu C, Tain Y. Endotoxemia exacerbates kidney injury and increases asymmetric dimethyl arginine in young bile ductligated rats. Shock. 2012;37(4):441-448. https://doi.org/10.1097/SHK.0b013e318244b787.

Shah N, Dhar D, Mohammed FEZ, Habtesion A, Davies NA, Jover-Cobos M, Macnaughtan J, Sharma V, Olde Damink SWM, Mookerjee RP, Jalan R. Prevention of acute kidney injury in a rodent model of cirrhosis following selective gut decontamination is associated with reduced renal TLR4 expression. J. Hepatol. 2012;56(5):1047-1053. https://doi.org/10.1016/j.jhep.2011.11.024.

Ancel D, Barraud H, Peyrin-Biroulet L, Bronowicki J. Intestinal permeability and cirrhosis. Gastroenterol. Clin. Biol. 2006;30(3):460-468. https://doi.org/10.1016/s0399-8320(06)73203-1.

Llovet JM, Bartolí R, March F, Planas R, Viñado B, Cabré E, Arnal J, Coll P, Ausina V, Gassull MA. Translocated intestinal bacteria cause spontaneous bacterial peritonitis in cirrhotic rats: molecular epidemiologic evidence. J. Hepatol. 2010;28(2):307-313. https://doi.org/10.1016/0168-8278(88)80018-7.

Hanouneh MA, Hanouneh IA, Hashash JG, Law R, Esfeh JM, Lopez R, Hazratjee N, Smith T, Zein NN. The role of rifaximin in the primary prophylaxis of spontaneous bacterial peritonitis in patients with liver cirrhosis. J. Clin. Gastroenterol. 2012;46(8):709-715. https://doi.org/10.1097/MCG.0b013e3182506dbb.

Soriano G, Guarner C, Tomàs A, Villanueva C, Torras X, González D, Sáinz S, Anguera A, Cussó X, Balanzó J, Vilardeii F. Norfloxacin prevents bacterial infection in cirrhotics with gastrointestinal hemorrhage. Gastroenterology. 2012;103(4):1267-1272. https://doi.org/10.1016/0016-5085(92)91514-5.

Wijdicks EF. Hepatic Encephalopathy. N. Engl. J. Med. 2016;375:1660-1670. https://doi.org/10.1056/NEJMra1600561.

Bajaj JS, Ridlon JM, Hylemon PB, Thacker LR, Heuman DM, Smith S, Sikaroodi M, Gillevet PM. Linkage of gut microbiome with cognition in hepatic encephalopathy. Am. J. Physiol. Gastrointest. Liver Physiol. 2012;302(1):168-175. https://doi.org/10.1152/ajpgi.00190.2011.

Murta V, Farías MI, Pitossi FJ, Ferrari СС. Chronic systemic IL-1β exacerbates central neuroinflammation independently of the blood-brain barrier integrity. J. Neuroimmunol. 2015;278:30-43. https://doi.org/10.1016/j.jneuroim.2014.11.023.

Ponziani FR, Gerardi V, Pecere S, D’Aversa F, Lopetuso L, Zocco MA, Pompili M, Gasbarrini A. Effect of rifaximin on gut microbiota composition in advanced liver disease and its complications. World J. Gastroenterol. 2015;21(43):12322-12333. https://doi.org/10.3748/wjg.v21.i43.12322.

Violi F, Lip GY, Cangemi R. Endotoxemia as a trigger of thrombosis in cirrhosis. Haematologica. 2016;101(4):162-163. https://doi.org/10.3324/haematol.2015.139972.

Carnevale R, Raparelli V, Nocella C, Bartimoccia S, Novo M, Severino A, De Falco E, Cammisotto V, Pasquale C, Crescioli C, Scavalli AS, Riggio O, Basili S, Violi F. Gut-derived endotoxin stimulates factor VIII secretion from endothelial cells. Implications for hypercoagulability in cirrhosis. J. Hepatol. 2017;67(5):950-956. https://doi.org/10.1016/j.jhep.2017.07.002.

Lumsden AB, Henderson JM, Kutner MH. Endotoxin levels measured by a chromogenic assay in portal, hepatic and peripheral venous blood in patients with cirrhosis. Hepatology. 1988;8(2):232-236. https://doi.org/10.1002/hep.1840080207.

Shibayama Y. Sinusoidal circulatory disturbance by microthrombosis as a cause of endotoxin–induced hepatic injury. J. Pathol. 2007;151(4):315-321.

Seki E, Schnabl B. Role of innate immunity and the microbiota in liver fibrosis: crosstalk between the liver and gut. J. Physiol. 2012;590(3):447-458. https://doi.org/10.1113/jphysi-ol.2011.219691.

Bishayee A. The role of inflammation and liver cancer. Adv. Exp. Med. Biol. 2014;816:401-435. https://doi.org/10.1007/978-3-0348-0837-8_16.

Liu W, Jing Y, Gao L, Li R, Yang X, Pan X, Yang Y, Meng Y, Hou X, Zhao Q, Han Z, Wei L. Lipopolysaccharide induces the differentiation of hepatic progenitor cells into myofibroblasts constitutes the hepatocarcinogenesis-associated microenvironment. Cell Death Differ. 2020;27(1):85-101. https://doi.org/10.1038/s41418-019-0340-7.

Maeda S, Kamata H, Luo L, Leffert, H, Karin M. IKK-beta couples hepatocyte death to cytokine-driven compensatory proliferation that promotes chemical hepatocarcinogenesis. Cell. 2010;121(7):977-990. https://doi.org/10.1016/j.cell.2005.04.014.

Ma-on C, Sanpavat A, Whongsiri P, Suwannasin S, Hirankarn N, Tangkijanich P, Boonla C. Oxidative stress indicated by elevated expression of Nrf2 and 8-OHdG promotes hepatocellular carcinoma progression. Med. Oncol. 2017;34(4):57. https://doi.org/10.1007/s12032-017-0914-5.

Ponziani FR, Bhoori S, Castelli C, Putignani L, Rivoltini L, Chierico FD, Sanguinetti M, Morelli D, Sterbini FP, Petito V, Reddel S, Calvani R, Camisaschi C, Picca A, Tuccitto A, Gasbarrini A, Pompili M, Mazzaferro V. Hepatocellular carcinoma is associated with gut microbiota profile and inflammation in nonalcoholic fatty liver disease. Hepatology. 2019;69(1):107-120. https://doi.org/10.1002/hep.30036.

Piñero F, Vazquez M, Baré P, Rohr C, Mendizabal M, Sciara M, Alonso C, Fay F, Silva M. A different gut microbiome linked to inflammation found in cirrhotic patients with and without hepatocellular carcinoma. Ann. Hepatol. 2019;18(3):480-487. https://doi.org/10.1016/j.aohep.2018.10.003.

Qin N, Yang F, Li A, Prifti E, Chen Y, Shao L, Guo J, Le Chatelier E, Yao J, Wu L, Zhou J, Ni S, Liu L, Pons N, Batto JM, Kennedy SP, Leonard P, Yuan C, Ding W, Chen Y, Hu X, Zheng B, Qian G, Xu W, Ehrlich D, et al. Alterations of the human gut microbiome in liver cirrhosis. Nature. 2014;513(7516):59-64. https://doi.org/10.1038/nature13568.

Zhang Z, Zhai H, Geng J, Yu R, Ren H, Fan H, Shi P. Large-scale survey of gut microbiota associated with MHE via 16S rRNA-based pyrosequencing. Am. J. Gastroenterol. 2013;108(10):1601-1611. https://doi.org/10.1038/ajg.2013.221.

Published
2021-01-13
How to Cite
1.
Savarina VA, Mitsura VM. THE ROLE OF THE GUT-LIVER AXIS IN LIVER CIRRHOSIS PATHOGENESIS AND COMPLICATIONS. journalHandG [Internet]. 2021Jan.13 [cited 2024Nov.24];4(2):151-9. Available from: http://hepatogastro.grsmu.by/index.php/journalHandG/article/view/155
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