{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T19:35:12Z","timestamp":1793043312213,"version":"4.5.0"},"reference-count":45,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2020,7,1]],"date-time":"2020-07-01T00:00:00Z","timestamp":1593561600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,7,1]],"date-time":"2020-07-01T00:00:00Z","timestamp":1593561600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["EN 1100\/2-1"],"award-info":[{"award-number":["EN 1100\/2-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.fr","clinicalkey.jp","clinicalkey.es","clinicalkey.com.au","clinicalkey.com","journal-of-hepatology.eu","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Hepatology"],"published-print":{"date-parts":[[2020,7]]},"DOI":"10.1016\/j.jhep.2020.01.011","type":"journal-article","created":{"date-parts":[[2020,1,24]],"date-time":"2020-01-24T19:31:23Z","timestamp":1579894283000},"page":"102-112","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":170,"title":["Toll-like receptor 4 is a therapeutic target for prevention and treatment of liver failure"],"prefix":"10.1016","volume":"73","author":[{"given":"Cornelius","family":"Engelmann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Sheikh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shreya","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Kondo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Loeffler-Wirth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu Bao","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Novelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Hall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annarein J.C.","family":"Kerbert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Macnaughtan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajeshwar","family":"Mookerjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abeba","family":"Habtesion","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Davies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tauhid","family":"Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saurabh","family":"Gupta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fausto","family":"Andreola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajiv","family":"Jalan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jhep.2020.01.011_bib1","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1053\/j.gastro.2013.02.042","article-title":"Acute-on-chronic liver failure is a distinct syndrome that develops in patients with\u00a0acute decompensation of cirrhosis","volume":"144","author":"Moreau","year":"2013","journal-title":"Gastroenterology"},{"key":"10.1016\/j.jhep.2020.01.011_bib2","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1186\/s13054-018-2156-0","article-title":"Validation of CLIF-C ACLF score to define a threshold for futility of intensive care support for patients with acute-on-chronic liver failure","volume":"22","author":"Engelmann","year":"2018","journal-title":"Crit Care"},{"key":"10.1016\/j.jhep.2020.01.011_bib3","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1016\/j.jhep.2014.08.010","article-title":"Cirrhosis-associated immune dysfunction: distinctive features and clinical relevance","volume":"61","author":"Albillos","year":"2014","journal-title":"J\u00a0Hepatol"},{"key":"10.1016\/j.jhep.2020.01.011_bib4","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1002\/hep.27779","article-title":"Systemic inflammatory response and serum lipopolysaccharide levels predict multiple organ failure and death in alcoholic hepatitis","volume":"62","author":"Michelena","year":"2015","journal-title":"Hepatology"},{"issue":"1","key":"10.1016\/j.jhep.2020.01.011_bib5","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1038\/s41598-019-57284-z","article-title":"Recombinant alkaline phosphatase prevents acute on chronic liver failure","volume":"10","author":"Engelmann","year":"2020","journal-title":"Sci Rep"},{"key":"10.1016\/j.jhep.2020.01.011_bib6","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1111\/liv.13023","article-title":"A\u00a0model of acute kidney injury in mice with cirrhosis and infection","volume":"36","author":"Carl","year":"2016","journal-title":"Liver Int"},{"key":"10.1016\/j.jhep.2020.01.011_bib7","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1002\/hep.510300515","article-title":"Increased sensitivity to endotoxemia in the bile duct-ligated cirrhotic Rat","volume":"30","author":"Harry","year":"1999","journal-title":"Hepatology"},{"key":"10.1016\/j.jhep.2020.01.011_bib8","doi-asserted-by":"crossref","first-page":"2525","DOI":"10.1056\/NEJMra1208937","article-title":"Acute liver failure","volume":"369","author":"Bernal","year":"2013","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.jhep.2020.01.011_bib9","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.cld.2006.05.010","article-title":"Acute liver failure: a review","volume":"10","author":"Khan","year":"2006","journal-title":"Clin Liver Dis"},{"key":"10.1016\/j.jhep.2020.01.011_bib10","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/S1499-3872(13)60029-6","article-title":"Ethyl pyruvate prevents inflammatory factors release and decreases intestinal permeability in rats with D-galactosamine-induced acute liver failure","volume":"12","author":"Wang","year":"2013","journal-title":"Hepatobiliary Pancreat Dis Int"},{"key":"10.1016\/j.jhep.2020.01.011_bib11","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.biopha.2016.06.036","article-title":"Curcumin alleviates lipopolysaccharide induced sepsis and liver failure by suppression of oxidative stress-related inflammation via PI3K\/AKT and NF-kappaB related signaling","volume":"83","author":"Zhong","year":"2016","journal-title":"Biomed Pharmacother"},{"key":"10.1016\/j.jhep.2020.01.011_bib12","first-page":"3231","article-title":"Thymosin alpha1 treatment reduces hepatic inflammation and inhibits hepatocyte apoptosis in rats with acute liver failure","volume":"15","author":"Yang","year":"2018","journal-title":"Exp Ther Med"},{"key":"10.1016\/j.jhep.2020.01.011_bib13","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1126\/science.282.5396.2085","article-title":"Defective LPS signaling in C3H\/HeJ and C57BL\/10ScCr mice: mutations in Tlr4 gene","volume":"282","author":"Poltorak","year":"1998","journal-title":"Science"},{"key":"10.1016\/j.jhep.2020.01.011_bib14","doi-asserted-by":"crossref","first-page":"8314","DOI":"10.3748\/wjg.v21.i27.8314","article-title":"TLR4-HMGB1-, MyD88- and TRIF-dependent signaling in mouse intestinal ischemia\/reperfusion injury","volume":"21","author":"Wang","year":"2015","journal-title":"World J Gastroenterol"},{"key":"10.1016\/j.jhep.2020.01.011_bib15","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1007\/s10753-017-0698-y","article-title":"Changes in expression of the membrane receptors CD14, MHC-II, SR-A, and TLR4 in tissue-specific monocytes\/macrophages following porphyromonas gingivalis-LPS stimulation","volume":"41","author":"Wu","year":"2018","journal-title":"Inflammation"},{"key":"10.1016\/j.jhep.2020.01.011_bib16","doi-asserted-by":"crossref","first-page":"29433","DOI":"10.1074\/jbc.M803905200","article-title":"Beta2-integrin-induced p38 MAPK activation is a key mediator in the CD14\/TLR4\/MD2-dependent uptake of lipopolysaccharide by hepatocytes","volume":"283","author":"Scott","year":"2008","journal-title":"J\u00a0Biol Chem"},{"key":"10.1016\/j.jhep.2020.01.011_bib17","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1124\/mol.110.068064","article-title":"TAK-242 (resatorvid), a small-molecule inhibitor of Toll-like receptor (TLR) 4 signaling, binds selectively to TLR4 and interferes with interactions between TLR4 and its adaptor molecules","volume":"79","author":"Matsunaga","year":"2011","journal-title":"Mol Pharmacol"},{"key":"10.1016\/j.jhep.2020.01.011_bib18","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1016\/j.jhep.2011.11.024","article-title":"Prevention of acute kidney injury in a rodent model of cirrhosis following selective gut decontamination is associated with reduced renal TLR4 expression","volume":"56","author":"Shah","year":"2012","journal-title":"J\u00a0Hepatol"},{"key":"10.1016\/j.jhep.2020.01.011_bib19","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1002\/lt.23655","article-title":"Role of toll-like receptor 4 in mediating multiorgan dysfunction in mice with acetaminophen induced acute liver failure","volume":"19","author":"Shah","year":"2013","journal-title":"Liver Transpl"},{"key":"10.1016\/j.jhep.2020.01.011_bib20","doi-asserted-by":"crossref","first-page":"2434","DOI":"10.3389\/fimmu.2018.02434","article-title":"Pharmacological inhibition of toll-like receptor-4 signaling by TAK242 prevents and induces regression of experimental organ fibrosis","volume":"9","author":"Bhattacharyya","year":"2018","journal-title":"Front Immunol"},{"key":"10.1016\/j.jhep.2020.01.011_bib21","doi-asserted-by":"crossref","first-page":"1808","DOI":"10.3389\/fimmu.2017.01808","article-title":"Positive feedback regulation between transglutaminase 2 and toll-like receptor 4 signaling in hepatic stellate cells correlates with liver fibrosis post schistosoma japonicum infection","volume":"8","author":"Wen","year":"2017","journal-title":"Front Immunol"},{"key":"10.1016\/j.jhep.2020.01.011_bib22","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.surg.2017.08.025","article-title":"Inhibition of Toll-like receptor 4 ameliorates experimental postischemic injury in the cholestatic liver through inhibition of high-mobility group box protein b1 (HMGB1) signaling","volume":"163","author":"Yokoi","year":"2018","journal-title":"Surgery"},{"key":"10.1016\/j.jhep.2020.01.011_bib23","doi-asserted-by":"crossref","first-page":"G244","DOI":"10.1152\/ajpgi.00366.2013","article-title":"Inhibition of Toll-like receptor 4 suppresses liver injury induced by biliary obstruction and subsequent intraportal lipopolysaccharide injection","volume":"306","author":"Oya","year":"2014","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"10.1016\/j.jhep.2020.01.011_bib24","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.biopha.2016.09.036","article-title":"TAK-242 treatment ameliorates liver ischemia\/reperfusion injury by inhibiting TLR4 signaling pathway in\u00a0a swine model of Maastricht-category-III cardiac death","volume":"84","author":"Shao","year":"2016","journal-title":"Biomed Pharmacother"},{"key":"10.1016\/j.jhep.2020.01.011_bib25","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1016\/j.jhep.2014.01.024","article-title":"Bacterial infections in cirrhosis: a position statement based on the EASL Special Conference 2013","volume":"60","author":"Jalan","year":"2014","journal-title":"J\u00a0Hepatol"},{"key":"10.1016\/j.jhep.2020.01.011_bib26","doi-asserted-by":"crossref","first-page":"S131","DOI":"10.1016\/j.jhep.2014.11.045","article-title":"Acute-on-chronic liver failure: a new syndrome that will re-classify cirrhosis","volume":"62","author":"Arroyo","year":"2015","journal-title":"J\u00a0Hepatol"},{"key":"10.1016\/j.jhep.2020.01.011_bib27","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1189\/jlb.0206086","article-title":"Pivotal advance: vasoactive intestinal peptide inhibits up-regulation of human monocyte TLR2 and TLR4 by LPS and differentiation of monocytes to macrophages","volume":"81","author":"Foster","year":"2007","journal-title":"J\u00a0Leukoc Biol"},{"key":"10.1016\/j.jhep.2020.01.011_bib28","doi-asserted-by":"crossref","first-page":"2118","DOI":"10.1002\/hep.23929","article-title":"Nuclear factor kappaB up-regulation of CCAAT\/enhancer-binding protein beta mediates hepatocyte resistance to tumor necrosis factor alpha toxicity","volume":"52","author":"Wang","year":"2010","journal-title":"Hepatology"},{"issue":"Suppl 2","key":"10.1016\/j.jhep.2020.01.011_bib29","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1111\/j.1440-1746.2011.07003.x","article-title":"Hepatoprotective and anti-inflammatory cytokines in alcoholic liver disease","volume":"27","author":"Gao","year":"2012","journal-title":"J\u00a0Gastroenterol Hepatol"},{"key":"10.1016\/j.jhep.2020.01.011_bib30","doi-asserted-by":"crossref","first-page":"G15","DOI":"10.1152\/ajpgi.90512.2008","article-title":"Role of Toll-like receptors 2, 4, and 9 in mediating neutrophil dysfunction in alcoholic hepatitis","volume":"296","author":"Stadlbauer","year":"2009","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"10.1016\/j.jhep.2020.01.011_bib31","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.jhep.2007.04.019","article-title":"Toll-like receptor-4 signaling and Kupffer cells play pivotal roles in the pathogenesis of non-alcoholic steatohepatitis","volume":"47","author":"Rivera","year":"2007","journal-title":"J\u00a0Hepatol"},{"key":"10.1016\/j.jhep.2020.01.011_bib32","doi-asserted-by":"crossref","first-page":"G433","DOI":"10.1152\/ajpgi.00163.2009","article-title":"Deficiency in myeloid differentiation factor-2 and toll-like receptor 4 expression attenuates nonalcoholic steatohepatitis and fibrosis in mice","volume":"300","author":"Csak","year":"2011","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"10.1016\/j.jhep.2020.01.011_bib33","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1038\/nm1663","article-title":"TLR4 enhances TGF-beta signaling and hepatic fibrosis","volume":"13","author":"Seki","year":"2007","journal-title":"Nat Med"},{"key":"10.1016\/j.jhep.2020.01.011_bib34","doi-asserted-by":"crossref","first-page":"221","DOI":"10.3389\/fimmu.2014.00221","article-title":"Role of toll-like receptors in immune activation and tolerance in the liver","volume":"5","author":"Nakamoto","year":"2014","journal-title":"Front Immunol"},{"key":"10.1016\/j.jhep.2020.01.011_bib35","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1053\/jhep.2003.50182","article-title":"Toll-like receptor 4 mediates inflammatory signaling by bacterial lipopolysaccharide in human hepatic stellate cells","volume":"37","author":"Paik","year":"2003","journal-title":"Hepatology"},{"key":"10.1016\/j.jhep.2020.01.011_bib36","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1097\/CCM.0b013e3181e7c5c9","article-title":"A\u00a0randomized, double-blind, placebo-controlled trial of TAK-242 for the treatment of severe sepsis","volume":"38","author":"Rice","year":"2010","journal-title":"Crit Care Med"},{"key":"10.1016\/j.jhep.2020.01.011_bib37","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.imbio.2016.10.002","article-title":"Both intrinsic and extrinsic apoptotic pathways are involved in Toll-like receptor 4 (TLR4)-induced cell death in monocytic THP-1 cells","volume":"222","author":"Liu","year":"2017","journal-title":"Immunobiology"},{"key":"10.1016\/j.jhep.2020.01.011_bib38","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1111\/j.1530-0277.2011.01720.x","article-title":"Inhibition of apoptosis protects mice from ethanol-mediated acceleration of early markers of CCl4 -induced fibrosis but not steatosis or inflammation","volume":"36","author":"Roychowdhury","year":"2012","journal-title":"Alcohol Clin Exp Res"},{"key":"10.1016\/j.jhep.2020.01.011_bib39","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.15252\/emmm.201403856","article-title":"A\u00a0positive feedback loop between RIP3 and JNK controls non-alcoholic steatohepatitis","volume":"6","author":"Gautheron","year":"2014","journal-title":"EMBO Mol Med"},{"key":"10.1016\/j.jhep.2020.01.011_bib40","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1053\/j.gastro.2014.07.018","article-title":"Cell death and cell death responses in liver disease: mechanisms and clinical relevance","volume":"147","author":"Luedde","year":"2014","journal-title":"Gastroenterology"},{"key":"10.1016\/j.jhep.2020.01.011_bib41","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/nrm3999","article-title":"Live to die another way: modes of programmed cell death and the signals emanating from dying cells","volume":"16","author":"Fuchs","year":"2015","journal-title":"Nat Rev Mol Cell Biol"},{"key":"10.1016\/j.jhep.2020.01.011_bib42","doi-asserted-by":"crossref","first-page":"e1975","DOI":"10.1038\/cddis.2015.316","article-title":"Role of necroptosis in the pathogenesis of solid organ injury","volume":"6","author":"Zhao","year":"2015","journal-title":"Cell Death Dis"},{"key":"10.1016\/j.jhep.2020.01.011_bib43","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1007\/s00109-015-1270-6","article-title":"The chemical inhibitors of cellular death, PJ34 and Necrostatin-1, down-regulate IL\u201333 expression in liver","volume":"93","author":"Arshad","year":"2015","journal-title":"J\u00a0Mol Med (Berl)"},{"key":"10.1016\/j.jhep.2020.01.011_bib44","doi-asserted-by":"crossref","first-page":"2294","DOI":"10.1007\/s10620-016-4132-3","article-title":"Dysfunction of circulating polymorphonuclear leukocytes and monocytes in ambulatory cirrhotics predicts patient outcome","volume":"61","author":"Sargenti","year":"2016","journal-title":"Dig Dis Sci"},{"key":"10.1016\/j.jhep.2020.01.011_bib45","doi-asserted-by":"crossref","first-page":"e11049","DOI":"10.1371\/journal.pone.0011049","article-title":"Functional contribution of elevated circulating and hepatic non-classical CD14CD16 monocytes to inflammation and human liver fibrosis","volume":"5","author":"Zimmermann","year":"2010","journal-title":"PLoS One"}],"container-title":["Journal of Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0168827820300283?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0168827820300283?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2024,5,25]],"date-time":"2024-05-25T19:15:33Z","timestamp":1716664533000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168827820300283"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7]]},"references-count":45,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,7]]}},"alternative-id":["S0168827820300283"],"URL":"https:\/\/doi.org\/10.1016\/j.jhep.2020.01.011","relation":{},"ISSN":["0168-8278"],"issn-type":[{"value":"0168-8278","type":"print"}],"subject":[],"published":{"date-parts":[[2020,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Toll-like receptor 4 is a therapeutic target for prevention and treatment of liver failure","name":"articletitle","label":"Article Title"},{"value":"Journal of Hepatology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jhep.2020.01.011","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}]}}