{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T21:59:51Z","timestamp":1787003991617,"version":"build-2736575974"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,1,4]],"date-time":"2017-01-04T00:00:00Z","timestamp":1483488000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,1,4]],"date-time":"2017-01-04T00:00:00Z","timestamp":1483488000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Systemic lipopolysaccharide (LPS) is implicated in increasing mortality in patients with alcoholic hepatitis but the underlying mechanisms are not well characterised. The objective of this study was to characterise neutrophil function, LPS and cytokine concentrations within the splanchnic circulation of alcoholic cirrhotic patients undergoing TIPSS insertion for variceal haemorrhage and correlate this with outcome. 26 patients with alcoholic cirrhosis and variceal haemorrhage were studied prior to and 1-hour after TIPSS insertion. Neutrophil function, LPS and cytokine concentrations were determined in arterial, hepatic venous (HV) and portal venous blood (PV). Significantly higher LPS concentrations and neutrophil reactive oxidant species (ROS) production were observed in PV vs HV blood. Cross-incubation of HV plasma with PV neutrophils resulted in reduced ROS production. Insertion of TIPSS was associated with a significant increase in arterial LPS concentrations and deterioration in neutrophil phagocytosis. Number of organ failures and arterial IL-6 concentrations at presentation were associated with increased mortality. The portal circulation has a distinct immunological milieu characterised by a pathological neutrophil phenotype and an anti-inflammatory cytokine profile associated with heightened LPS levels. TIPSS insertion renders this neutrophil functional defect systemic, associated with an increase in arterial LPS and a susceptibility to sepsis.<\/jats:p>","DOI":"10.1038\/srep40157","type":"journal-article","created":{"date-parts":[[2017,1,4]],"date-time":"2017-01-04T05:09:42Z","timestamp":1483506582000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Lipopolysaccharide-Induced Neutrophil Dysfunction Following Transjugular Intrahepatic Portosystemic Stent Shunt (TIPSS) Insertion is Associated with Organ Failure and Mortality"],"prefix":"10.1038","volume":"7","author":[{"given":"Jane","family":"Macnaughtan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajeshwar P.","family":"Mookerjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Schalk","family":"van der Merwe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajiv","family":"Jalan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,1,4]]},"reference":[{"key":"BFsrep40157_CR1","doi-asserted-by":"publisher","first-page":"1024","DOI":"10.1038\/labinvest.2010.60","volume":"90","author":"CJ Steib","year":"2010","unstructured":"Steib, C. J. et al. Intraperitoneal LPS amplifies portal hypertension in rat liver fibrosis. Lab Invest. 90, 1024\u201332 (2010).","journal-title":"Lab Invest."},{"key":"BFsrep40157_CR2","doi-asserted-by":"publisher","first-page":"1324","DOI":"10.1038\/nm1663","volume":"13","author":"E Seki","year":"2007","unstructured":"Seki, E. et al. TLR4 enhances TGF-beta signaling and hepatic fibrosis. Nat Med. 13, 1324\u201332 (2007).","journal-title":"Nat Med"},{"key":"BFsrep40157_CR3","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1053\/jhep.2003.50038","volume":"37","author":"A Albillos","year":"2003","unstructured":"Albillos, A. et al. Increased LPS binding protein in cirrhotic patients with marked immune and hemodynamic derangement. Hepatology 37, 208\u201317 (2003).","journal-title":"Hepatology"},{"key":"BFsrep40157_CR4","doi-asserted-by":"publisher","first-page":"1655","DOI":"10.1002\/hep.510290608","volume":"29","author":"B Bernard","year":"1999","unstructured":"Bernard, B. et al. Antibiotic prophylaxis for the prevention of bacterial infections in cirrhotic patients with gastroin-testinal bleeding: a meta-analysis. Hepatology 29, 1655\u201361 (1999).","journal-title":"Hepatology"},{"key":"BFsrep40157_CR5","doi-asserted-by":"publisher","first-page":"746","DOI":"10.1002\/hep.20126","volume":"39","author":"MC Hou","year":"2004","unstructured":"Hou, M. C. et al. Antibiotic prophylaxis after endoscopic therapy prevents re-bleeding in acute variceal hemorrhage: a randomized trial. Hepatology. 39, 746\u201353 (2004).","journal-title":"Hepatology."},{"key":"BFsrep40157_CR6","doi-asserted-by":"publisher","first-page":"1182","DOI":"10.1136\/gut.52.8.1182","volume":"52","author":"RP Mookerjee","year":"2003","unstructured":"Mookerjee, R. P. et al. Tumour necrosis factor alpha is an important mediator of portal and systemic haemodynamic derangements in alcoholic hepatitis. Gut. 52, 1182\u20137 (2003).","journal-title":"Gut."},{"key":"BFsrep40157_CR7","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1097\/MEG.0b013e328351db6e","volume":"24","author":"C Mortensen","year":"2012","unstructured":"Mortensen, C., Andersen, O., Krag, A., Bendtsen, F. & M\u00f8ller, S. High-sensitivity C-reactive protein levels predict survival and are related to haemodynamics in alcoholic cirrhosis. Eur J Gastroenterol Hepatol 24, 619\u201326 (2012).","journal-title":"Eur J Gastroenterol Hepatol"},{"key":"BFsrep40157_CR8","doi-asserted-by":"publisher","first-page":"1426","DOI":"10.1053\/j.gastro.2013.02.042","volume":"144","author":"R Moreau","year":"2013","unstructured":"Moreau, R. et al. Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decom-pensation of cirrhosis. Gastroenterology. 144, 1426\u201337 (2013).","journal-title":"Gastroenterology."},{"key":"BFsrep40157_CR9","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1111\/j.1365-2249.2009.03916.x","volume":"156","author":"A Lemmers","year":"2009","unstructured":"Lemmers, A. et al. An inhibitor of interleukin-6 trans-signalling, sgp130, contributes to impaired acute phase re-sponse in human chronic liver disease. Clin Exp Immunol 156, 518\u2013527 (2009).","journal-title":"Clin Exp Immunol"},{"key":"BFsrep40157_CR10","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1111\/liv.12559","volume":"35","author":"G Mehta","year":"2015","unstructured":"Mehta, G., Mookerjee, R. P., Sharma, V. & Jalan, R. Systemic inflammation is associated with increased intrahepatic re-sistance and mortality in alcohol-related acute-on-chronic liver failure. Liver Int. 35, 724\u201334 (2015).","journal-title":"Liver Int."},{"key":"BFsrep40157_CR11","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1002\/hep.27779","volume":"62","author":"J Michelena","year":"2015","unstructured":"Michelena, J. et al. Systemic inflammatory response and serum lipopolysaccharide levels predict multiple organ failure and death in alcoholic hepatitis. Hepatology. 62, 762\u201372 (2015).","journal-title":"Hepatology."},{"key":"BFsrep40157_CR12","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/j.jhep.2010.06.042","volume":"54","author":"R Jalan","year":"2011","unstructured":"Jalan, R. et al. Acute endotoxemia following transjugular intrahepatic stent-shunt insertion is associated with sys-temic and cerebral vasodilatation with increased whole body nitric oxide production in critically ill cirrhotic patients. J Hepatol. 54, 265\u201371 (2011).","journal-title":"J Hepatol."},{"key":"BFsrep40157_CR13","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1053\/j.gastro.2007.06.065","volume":"133","author":"J Fernandez","year":"2007","unstructured":"Fernandez, J. et al. Primary prophylaxis of spontaneous bacterial peritonitis delays hepatorenal syndrome and improves survival in cirrhosis. Gastroenterology. 133, 818\u201324 (2007).","journal-title":"Gastroenterology."},{"key":"BFsrep40157_CR14","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/S0168-8278(87)80003-X","volume":"4","author":"C Bode","year":"1987","unstructured":"Bode, C., Kugler, V. & Bode, J. C. Endotoxemia in patients with alcoholic and non-alcoholic cirrhosis and in subjects with no evidence of chronic liver disease following acute alcohol excess. J Hepatol. 4, 8\u201314 (1987).","journal-title":"J Hepatol."},{"key":"BFsrep40157_CR15","doi-asserted-by":"publisher","first-page":"1399","DOI":"10.1038\/ajg.2015.313","volume":"110","author":"J Macnaughtan","year":"2015","unstructured":"Macnaughtan, J. & Jalan, R. Clinical and pathophysiological consequences of alterations in the microbiome in cirrhosis. Am J Gastroenterol. 110, 1399\u2013410 (2015).","journal-title":"Am J Gastroenterol"},{"key":"BFsrep40157_CR16","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1002\/hep.21737","volume":"46","author":"RP Mookerjee","year":"2007","unstructured":"Mookerjee, R. P. et al. Neutrophil dysfunction in alcoholic hepatitis superimposed on cirrhosis is reversible and pre-dicts the outcome. Hepatology. 46, 831\u201340 (2007).","journal-title":"Hepatology."},{"key":"BFsrep40157_CR17","doi-asserted-by":"publisher","first-page":"G15","DOI":"10.1152\/ajpgi.90512.2008","volume":"296","author":"V Stadlbauer","year":"2009","unstructured":"Stadlbauer, V. et al. Role of Toll-like receptors 2, 4, and 9 in mediating neutrophil dysfunction in alcoholic hepatitis. Am J Physiol Gastrointest Liver Physiol. 296, G15\u201322 (2009).","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"BFsrep40157_CR18","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1155\/MI.2005.101","volume":"2","author":"MA Aller","year":"2005","unstructured":"Aller, M. A. et al. Proinflammatory liver and antiinflammatory intestinal mediators involved in portal hypertensive rats. Mediators Inflamm. 2, 101\u201311 (2005).","journal-title":"Mediators Inflamm."},{"key":"BFsrep40157_CR19","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1053\/jhep.2002.31656","volume":"35","author":"A Ramachandran","year":"2002","unstructured":"Ramachandran, A. et al. Intestinal mucosal alterations in experimental cirrhosis in the rat: role of oxygen free radicals. Hepatology. 35, 622\u20139 (2002).","journal-title":"Hepatology."},{"key":"BFsrep40157_CR20","first-page":"92","volume":"2","author":"B Gao","year":"2005","unstructured":"Gao, B. Cytokines, STATs and liver disease. Cell Mol Immunol. 2, 92\u2013100 (2005).","journal-title":"Cell Mol Immunol"},{"key":"BFsrep40157_CR21","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1016\/j.jhep.2014.11.012","volume":"62","author":"R Jalan","year":"2015","unstructured":"Jalan, R. et al. The CLIF Consortium Acute Decompensation score (CLIF-C ADs) for prognosis of hospitalised cirrhotic patients without acute-on-chronic liver failure. J Hepatol. 62, 831\u201340 (2015).","journal-title":"J Hepatol."},{"key":"BFsrep40157_CR22","doi-asserted-by":"publisher","first-page":"S1112","DOI":"10.1016\/S0016-5085(16)33756-8","volume":"150","author":"R Ghaoui","year":"2016","unstructured":"Ghaoui, R. et al. Acute on Chronic Liver Failure (ACLF) in Patients Presenting With Variceal Bleeding: A 5 Year, Multi-Center US Experience. Gastroenterology 150 S1, S1112 (2016).","journal-title":"Gastroenterology"},{"key":"BFsrep40157_CR23","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1016\/S1665-2681(19)31278-5","volume":"14","author":"LC Casadaban","year":"2015","unstructured":"Casadaban, L. C. et al. MELD score for prediction of survival after emergent TIPS for acute variceal hemorrhage: derivation and validation in a 101-patient cohort. Ann Hepatol. 14, 380\u20138 (2015).","journal-title":"Ann Hepatol."},{"key":"BFsrep40157_CR24","doi-asserted-by":"publisher","first-page":"2370","DOI":"10.1056\/NEJMoa0910102","volume":"362","author":"JC Garcia-Pagan","year":"2010","unstructured":"Garcia-Pagan, J. C. et al. Early use of TIPS in patients with cirrhosis and variceal bleeding. NEJM 362, 2370\u20132379 (2010).","journal-title":"NEJM"},{"key":"BFsrep40157_CR25","doi-asserted-by":"publisher","first-page":"928","DOI":"10.1016\/S0168-8278(97)80333-9","volume":"27","author":"R Jalan","year":"1997","unstructured":"Jalan, R., Dabos, K., Redhead, D. N., Lee, A. & Hayes, P. C. Elevation of intracranial pressure following transjugular intrahepatic portosystemic stent-shunt for variceal haemorrhage. J Hepatol. 27, 928\u201333 (1997).","journal-title":"J Hepatol."},{"key":"BFsrep40157_CR26","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1136\/gut.48.3.390","volume":"48","author":"G Pomier-Layrargues","year":"2001","unstructured":"Pomier-Layrargues, G. et al. Transjugular intrahepatic portosystemic shunt (TIPS) versus endoscopic variceal ligation in the prevention of variceal rebleeding in patients with cirrhosis: a randomised trial. Gut. 48, 390\u20136 (2001).","journal-title":"Gut."}],"updated-by":[{"DOI":"10.1038\/srep45253","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2017,4,28]],"date-time":"2017-04-28T00:00:00Z","timestamp":1493337600000}},{"DOI":"10.1038\/srep46990","type":"erratum","label":"Erratum","source":"publisher","updated":{"date-parts":[[2018,5,31]],"date-time":"2018-05-31T00:00:00Z","timestamp":1527724800000}}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep40157.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep40157","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep40157.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T20:00:39Z","timestamp":1671825639000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep40157"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,1,4]]},"references-count":26,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,3,15]]}},"alternative-id":["BFsrep40157"],"URL":"https:\/\/doi.org\/10.1038\/srep40157","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,1,4]]},"assertion":[{"value":"19 September 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 December 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 January 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 May 2018","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Update","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A correction has been published and is appended to both the HTML and PDF versions of this paper. The error has been fixed in the paper.","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 April 2017","order":7,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Update","order":8,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A correction has been published and is appended to both the HTML and PDF versions of this paper. The error has been fixed in the paper.","order":9,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 May 2018","order":10,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Erratum","order":11,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Scientific Reports 7: Article number: 40157; published online: 04 January 2017; updated: 31 May 2018 In the Corrigendum published 28 April 2017, the author Schalk van der Merwe was incorrectly indexed. This error has now been corrected.","order":12,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Rajiv Jalan has served on the Scientific Advisory Board for Conatus Pharma. He has received lecture fees from Gambro and has an on-going research collaboration with Gambro, Grifols and is the Principal Investigator of an Industry sponsored study (Sequana Medical). He is also inventor for the drug, L-ornithine phenyl acetate (OCR-002) which UCL has licensed to Ocera Therapeutics. He is also the founder of UCL spin-out company Yaqrit ltd. and Cyberliver ltd.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"40157"}}