{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:01:22Z","timestamp":1792000882692,"version":"4.4.0"},"reference-count":26,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2015,3,1]],"date-time":"2015-03-01T00:00:00Z","timestamp":1425168000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2015,3,1]],"date-time":"2015-03-01T00:00:00Z","timestamp":1425168000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100006135","name":"ERAB: The European Foundation for Alcohol Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006135","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012111","name":"Foundation for Liver Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012111","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006135","name":"ERAB: The European Foundation for Alcohol Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006135","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","gastrojournal.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Gastroenterology"],"published-print":{"date-parts":[[2015,3]]},"DOI":"10.1053\/j.gastro.2014.11.041","type":"journal-article","created":{"date-parts":[[2014,12,2]],"date-time":"2014-12-02T16:49:28Z","timestamp":1417538968000},"page":"590-602.e10","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":175,"title":["Blockade of PD1 and TIM3 Restores Innate and Adaptive Immunity in Patients With Acute Alcoholic Hepatitis"],"prefix":"10.1053","volume":"148","author":[{"given":"Lee J.L.","family":"Markwick","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Riva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer M.","family":"Ryan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Cooksley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Palma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom H.","family":"Tranah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Godhev K.","family":"Manakkat Vijay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikhil","family":"Vergis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Thursz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Evans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin","family":"Wright","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Tarff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"O\u2019Grady","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debbie L.","family":"Shawcross","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilpa","family":"Chokshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1053\/j.gastro.2014.11.041_bib1","series-title":"Global status report on alcohol and health","year":"2011"},{"issue":"Suppl 1","key":"10.1053\/j.gastro.2014.11.041_bib2","doi-asserted-by":"crossref","first-page":"S39","DOI":"10.1016\/S0168-8278(12)60005-1","article-title":"Management of alcoholic hepatitis","volume":"56","author":"Mathurin","year":"2012","journal-title":"J\u00a0Hepatol"},{"issue":"Suppl 1","key":"10.1053\/j.gastro.2014.11.041_bib3","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1111\/jgh.12030","article-title":"Alcoholic liver disease: pathogenesis, management, and novel targets for therapy","volume":"28","author":"Orman","year":"2013","journal-title":"J\u00a0Gastroenterol Hepatol"},{"key":"10.1053\/j.gastro.2014.11.041_bib4","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1146\/annurev.immunol.26.021607.090331","article-title":"PD-1 and its ligands in tolerance and immunity","volume":"26","author":"Keir","year":"2008","journal-title":"Annu Rev Immunol"},{"key":"10.1053\/j.gastro.2014.11.041_bib5","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1002\/hep.22419","article-title":"Programmed death 1 expression during antiviral treatment of chronic hepatitis B: impact of hepatitis B\u00a0e-antigen seroconversion","volume":"48","author":"Evans","year":"2008","journal-title":"Hepatology"},{"key":"10.1053\/j.gastro.2014.11.041_bib6","doi-asserted-by":"crossref","first-page":"449","DOI":"10.3389\/fimmu.2013.00449","article-title":"Tim-3: an activation marker and activation limiter of innate immune cells","volume":"4","author":"Han","year":"2013","journal-title":"Front Immunol"},{"key":"10.1053\/j.gastro.2014.11.041_bib7","doi-asserted-by":"crossref","first-page":"4546","DOI":"10.1172\/JCI43127","article-title":"Tim-3 expression on PD-1+ HCV-specific human CTLs is associated with viral persistence, and its blockade restores hepatocyte-directed in\u00a0vitro cytotoxicity","volume":"120","author":"McMahan","year":"2010","journal-title":"J\u00a0Clin Invest"},{"key":"10.1053\/j.gastro.2014.11.041_bib8","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.1084\/jem.20100637","article-title":"Upregulation of Tim-3 and PD-1 expression is associated with tumor antigen-specific CD8+ T cell dysfunction in melanoma patients","volume":"207","author":"Fourcade","year":"2010","journal-title":"J\u00a0Exp Med"},{"key":"10.1053\/j.gastro.2014.11.041_bib9","first-page":"1","article-title":"Surgery and portal hypertension","volume":"1","author":"Child","year":"1964","journal-title":"Major Probl Clin Surg"},{"key":"10.1053\/j.gastro.2014.11.041_bib10","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1038\/nprot.2010.111","article-title":"Preparation and incubation of precision-cut liver and intestinal slices for application in drug metabolism and toxicity studies","volume":"5","author":"de Graaf","year":"2010","journal-title":"Nat Protoc"},{"key":"10.1053\/j.gastro.2014.11.041_bib11","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1006\/abbi.1995.1400","article-title":"Establishment of a recombinant hepatic cell line stably expressing alcohol dehydrogenase","volume":"321","author":"Clemens","year":"1995","journal-title":"Arch Biochem Biophys"},{"key":"10.1053\/j.gastro.2014.11.041_bib12","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1002\/hep.26102","article-title":"Circulating neutrophil dysfunction in acute liver failure","volume":"57","author":"Taylor","year":"2013","journal-title":"Hepatology"},{"key":"10.1053\/j.gastro.2014.11.041_bib13","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1053\/jhep.2001.22172","article-title":"A\u00a0model to predict survival in patients with end-stage liver disease","volume":"33","author":"Kamath","year":"2001","journal-title":"Hepatology"},{"key":"10.1053\/j.gastro.2014.11.041_bib14","doi-asserted-by":"crossref","first-page":"175","DOI":"10.3389\/fimmu.2014.00175","article-title":"Know thyself: NK-cell inhibitory receptors prompt self-tolerance, education, and viral control","volume":"5","author":"Nash","year":"2014","journal-title":"Front Immunol"},{"key":"10.1053\/j.gastro.2014.11.041_bib15","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/nm.2106","article-title":"Programmed death-1-induced interleukin-10 production by monocytes impairs CD4+ T cell activation during HIV infection","volume":"16","author":"Said","year":"2010","journal-title":"Nat Med"},{"key":"10.1053\/j.gastro.2014.11.041_bib16","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.it.2011.03.010","article-title":"The Th1 life cycle: molecular control of IFN-gamma to IL-10 switching","volume":"32","author":"Cope","year":"2011","journal-title":"Trends Immunol"},{"key":"10.1053\/j.gastro.2014.11.041_bib17","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1038\/nri3552","article-title":"Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy","volume":"13","author":"Hotchkiss","year":"2013","journal-title":"Nat Rev Immunol"},{"key":"10.1053\/j.gastro.2014.11.041_bib18","doi-asserted-by":"crossref","first-page":"361501","DOI":"10.1155\/2013\/361501","article-title":"PD-L1 blockade attenuated sepsis-induced liver injury in a mouse cecal ligation and puncture model","volume":"2013","author":"Zhu","year":"2013","journal-title":"Mediators Inflamm"},{"key":"10.1053\/j.gastro.2014.11.041_bib19","doi-asserted-by":"crossref","first-page":"4221","DOI":"10.4049\/jimmunol.1302569","article-title":"TLR4 ligands lipopolysaccharide and monophosphoryl lipid a differentially regulate effector and memory CD8+ T cell differentiation","volume":"192","author":"Cui","year":"2014","journal-title":"J\u00a0Immunol"},{"key":"10.1053\/j.gastro.2014.11.041_bib20","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.imlet.2009.09.002","article-title":"TLR-9 signaling and TCR stimulation co-regulate CD8(+) T cell-associated PD-1 expression","volume":"127","author":"Wong","year":"2009","journal-title":"Immunol Lett"},{"key":"10.1053\/j.gastro.2014.11.041_bib21","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1002\/hep.26933","article-title":"Secretory leukocyte protease inhibitor: a pivotal mediator of anti-inflammatory responses in acetaminophen-induced acute liver failure","volume":"59","author":"Antoniades","year":"2014","journal-title":"Hepatology"},{"key":"10.1053\/j.gastro.2014.11.041_bib22","doi-asserted-by":"crossref","first-page":"546","DOI":"10.3748\/wjg.v8.i3.546","article-title":"Relationship between lymphocyte apoptosis and endotoxin translocation after thermal injury in rats","volume":"8","author":"Xia","year":"2002","journal-title":"World J Gastroenterol"},{"key":"10.1053\/j.gastro.2014.11.041_bib23","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1002\/hep.1840080207","article-title":"Endotoxin levels measured by a chromogenic assay in portal, hepatic and peripheral venous blood in patients with cirrhosis","volume":"8","author":"Lumsden","year":"1988","journal-title":"Hepatology"},{"key":"10.1053\/j.gastro.2014.11.041_bib24","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s00011-010-0233-1","article-title":"Intrahepatic levels of PD-1\/PD-L correlate with liver inflammation in chronic hepatitis B","volume":"60","author":"Chen","year":"2011","journal-title":"Inflamm Res"},{"key":"10.1053\/j.gastro.2014.11.041_bib25","doi-asserted-by":"crossref","first-page":"R220","DOI":"10.1186\/cc9354","article-title":"PD-L1 blockade improves survival in experimental sepsis by inhibiting lymphocyte apoptosis and reversing monocyte dysfunction","volume":"14","author":"Zhang","year":"2010","journal-title":"Crit Care"},{"key":"10.1053\/j.gastro.2014.11.041_bib26","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1002\/hep.21737","article-title":"Neutrophil dysfunction in alcoholic hepatitis superimposed on cirrhosis is reversible and predicts the outcome","volume":"46","author":"Mookerjee","year":"2007","journal-title":"Hepatology"}],"container-title":["Gastroenterology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0016508514014784?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0016508514014784?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T15:10:15Z","timestamp":1758035415000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0016508514014784"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,3]]},"references-count":26,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2015,3]]}},"alternative-id":["S0016508514014784"],"URL":"https:\/\/doi.org\/10.1053\/j.gastro.2014.11.041","relation":{},"ISSN":["0016-5085"],"issn-type":[{"value":"0016-5085","type":"print"}],"subject":[],"published":{"date-parts":[[2015,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Blockade of PD1 and TIM3 Restores Innate and Adaptive Immunity in Patients With Acute Alcoholic Hepatitis","name":"articletitle","label":"Article Title"},{"value":"Gastroenterology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1053\/j.gastro.2014.11.041","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}