{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T03:09:24Z","timestamp":1773889764905,"version":"3.50.1"},"reference-count":48,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AA012863"],"award-info":[{"award-number":["R01AA012863"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["F32AA031430"],"award-info":[{"award-number":["F32AA031430"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P20GM144269"],"award-info":[{"award-number":["P20GM144269"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ajp.amjpathol.org","clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The American Journal of Pathology"],"published-print":{"date-parts":[[2026,1]]},"DOI":"10.1016\/j.ajpath.2025.10.004","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T07:52:28Z","timestamp":1761897148000},"page":"272-287","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"title":["Liver Macrophage Changes during Early Adaptation to Alcohol Exposure"],"prefix":"10.1016","volume":"196","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2013-0131","authenticated-orcid":false,"given":"Kyle","family":"Yuquimpo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janice","family":"Averilla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Priyanka","family":"Ghosh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheetalnath","family":"Rooge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8716-0854","authenticated-orcid":false,"given":"Isabel A.","family":"Pulido Ruiz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Winston","family":"Dunn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sumedha","family":"Gunewardena","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8401-6661","authenticated-orcid":false,"given":"Ann L.","family":"Wozniak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irina","family":"Tikhanovich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven A.","family":"Weinman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.ajpath.2025.10.004_bib1","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1097\/HEP.0000000000000899","article-title":"Alcohol-associated liver disease-global epidemiology","volume":"80","author":"\u00c5berg","year":"2024","journal-title":"Hepatology"},{"key":"10.1016\/j.ajpath.2025.10.004_bib2","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.jceh.2022.09.001","article-title":"Epidemiology and disease burden of alcohol associated liver disease","volume":"13","author":"Aslam","year":"2023","journal-title":"J Clin Exp Hepatol"},{"key":"10.1016\/j.ajpath.2025.10.004_bib3","doi-asserted-by":"crossref","first-page":"e316","DOI":"10.1016\/S2468-2667(20)30062-1","article-title":"Projected prevalence and mortality associated with alcohol-related liver disease in the USA, 2019-40: a modelling study","volume":"5","author":"Julien","year":"2020","journal-title":"Lancet Public Health"},{"key":"10.1016\/j.ajpath.2025.10.004_bib4","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2020.22942","article-title":"Changes in adult alcohol use and consequences during the COVID-19 pandemic in the US","volume":"3","author":"Pollard","year":"2020","journal-title":"JAMA Netw Open"},{"key":"10.1016\/j.ajpath.2025.10.004_bib5","doi-asserted-by":"crossref","first-page":"2437","DOI":"10.1001\/archinte.166.22.2437","article-title":"Alcohol dosing and total mortality in men and women: an updated meta-analysis of 34 prospective studies","volume":"166","author":"Di Castelnuovo","year":"2006","journal-title":"Arch Intern Med"},{"key":"10.1016\/j.ajpath.2025.10.004_bib6","doi-asserted-by":"crossref","first-page":"2315","DOI":"10.1016\/j.jacc.2023.04.015","article-title":"Reduced stress-related neural network activity mediates the effect of alcohol on cardiovascular risk","volume":"81","author":"Mezue","year":"2023","journal-title":"J Am Coll Cardiol"},{"key":"10.1016\/j.ajpath.2025.10.004_bib7","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1016\/S0140-6736(18)30134-X","article-title":"Risk thresholds for alcohol consumption: combined analysis of individual-participant data for 599 912 current drinkers in 83 prospective studies","volume":"391","author":"Wood","year":"2018","journal-title":"Lancet"},{"key":"10.1016\/j.ajpath.2025.10.004_bib8","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.ebiom.2016.04.023","article-title":"Ethnicity matters: a systematic review and meta-analysis of the non-linear relationship between alcohol consumption and prevalence and incidence of hepatic steatosis","volume":"8","author":"Roerecke","year":"2016","journal-title":"EBioMedicine"},{"key":"10.1016\/j.ajpath.2025.10.004_bib9","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1002\/hep.30864","article-title":"Risks of light and moderate alcohol use in fatty liver disease: follow-up of population cohorts","volume":"71","author":"\u00c5berg","year":"2020","journal-title":"Hepatology"},{"key":"10.1016\/j.ajpath.2025.10.004_bib10","doi-asserted-by":"crossref","DOI":"10.1097\/HC9.0000000000000491","article-title":"Liver macrophages revisited: the expanding universe of versatile responses in a spatiotemporal context","volume":"8","author":"Guillot","year":"2024","journal-title":"Hepatol Commun"},{"key":"10.1016\/j.ajpath.2025.10.004_bib11","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/bs.ircmb.2022.04.006","article-title":"Macrophages as key regulators of liver health and disease","volume":"368","author":"Papachristoforou","year":"2022","journal-title":"Int Rev Cell Mol Biol"},{"key":"10.1016\/j.ajpath.2025.10.004_bib12","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1189\/jlb.6A0114-004RR","article-title":"Chronic alcohol ingestion modulates hepatic macrophage populations and functions in mice","volume":"96","author":"Wang","year":"2014","journal-title":"J Leukoc Biol"},{"key":"10.1016\/j.ajpath.2025.10.004_bib13","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1097\/HEP.0000000000000918","article-title":"Kupffer cell diversity maintains liver function in alcohol-associated liver disease","volume":"81","author":"Sasaki","year":"2025","journal-title":"Hepatology"},{"key":"10.1016\/j.ajpath.2025.10.004_bib14","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.immuni.2014.12.020","article-title":"Liver-resident macrophage necroptosis orchestrates type 1 microbicidal inflammation and type-2-mediated tissue repair during bacterial infection","volume":"42","author":"Bleriot","year":"2015","journal-title":"Immunity"},{"key":"10.1016\/j.ajpath.2025.10.004_bib15","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/j.immuni.2019.08.017","article-title":"Stellate cells, hepatocytes, and endothelial cells imprint the Kupffer cell identity on monocytes colonizing the liver macrophage niche","volume":"51","author":"Bonnardel","year":"2019","journal-title":"Immunity"},{"key":"10.1016\/j.ajpath.2025.10.004_bib16","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1016\/j.immuni.2020.04.001","article-title":"Niche-specific reprogramming of epigenetic landscapes drives myeloid cell diversity in nonalcoholic steatohepatitis","volume":"52","author":"Seidman","year":"2020","journal-title":"Immunity"},{"key":"10.1016\/j.ajpath.2025.10.004_bib17","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1038\/s41590-020-00849-2","article-title":"Does tissue imprinting restrict macrophage plasticity?","volume":"22","author":"Guilliams","year":"2021","journal-title":"Nat Immunol"},{"key":"10.1016\/j.ajpath.2025.10.004_bib18","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms10321","article-title":"Bone marrow-derived monocytes give rise to self-renewing and fully differentiated Kupffer cells","volume":"7","author":"Scott","year":"2016","journal-title":"Nat Commun"},{"key":"10.1016\/j.ajpath.2025.10.004_bib19","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.1097\/HEP.0000000000000520","article-title":"A multisociety Delphi consensus statement on new fatty liver disease nomenclature","volume":"78","author":"Rinella","year":"2023","journal-title":"Hepatology"},{"key":"10.1016\/j.ajpath.2025.10.004_bib20","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1080\/17474124.2025.2508963","article-title":"Reviewing the function of macrophages in liver disease","volume":"19","author":"Chen","year":"2025","journal-title":"Expert Rev Gastroenterol Hepatol"},{"key":"10.1016\/j.ajpath.2025.10.004_bib21","article-title":"Understanding the complex macrophage landscape in MASLD","volume":"6","author":"De Ponti","year":"2024","journal-title":"JHEP Rep"},{"key":"10.1016\/j.ajpath.2025.10.004_bib22","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/j.immuni.2020.08.004","article-title":"Osteopontin expression identifies a subset of recruited macrophages distinct from Kupffer cells in the fatty liver","volume":"53","author":"Remmerie","year":"2020","journal-title":"Immunity"},{"key":"10.1016\/j.ajpath.2025.10.004_bib23","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.immuni.2020.06.003","article-title":"Impaired Kupffer cell self-renewal alters the liver response to lipid overload during non-alcoholic steatohepatitis","volume":"53","author":"Tran","year":"2020","journal-title":"Immunity"},{"key":"10.1016\/j.ajpath.2025.10.004_bib24","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1016\/j.cell.2019.05.054","article-title":"Lipid-associated macrophages control metabolic homeostasis in a Trem2-dependent manner","volume":"178","author":"Jaitin","year":"2019","journal-title":"Cell"},{"key":"10.1016\/j.ajpath.2025.10.004_bib25","doi-asserted-by":"crossref","first-page":"51s","DOI":"10.1111\/j.1530-0277.2001.tb02418.x","article-title":"Kupffer cell sensitization by alcohol involves increased permeability to gut-derived endotoxin","volume":"25","author":"Enomoto","year":"2001","journal-title":"Alcohol Clin Exp Res"},{"key":"10.1016\/j.ajpath.2025.10.004_bib26","first-page":"1360","article-title":"Long-term alcohol exposure changes sensitivity of rat Kupffer cells to lipopolysaccharide","volume":"25","author":"Enomoto","year":"2001","journal-title":"Alcohol Clin Exp Res"},{"issue":"Suppl 1","key":"10.1016\/j.ajpath.2025.10.004_bib27","first-page":"S53","article-title":"Regulation of macrophage activation in alcoholic liver disease","volume":"22","author":"Thakur","year":"2007","journal-title":"J Gastroenterol Hepatol"},{"key":"10.1016\/j.ajpath.2025.10.004_bib28","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1002\/hep.31759","article-title":"Gene deconvolution reveals aberrant liver regeneration and immune cell infiltration in alcohol-associated hepatitis","volume":"74","author":"Kim","year":"2021","journal-title":"Hepatology"},{"key":"10.1016\/j.ajpath.2025.10.004_bib29","series-title":"Committee for the Update of the Guide for the Care and Use of Laboratory Animals; National Research Council: Guide for the Care and Use of Laboratory Animals: Eighth Edition. Washington, DC, National Academies Press","year":"2011"},{"key":"10.1016\/j.ajpath.2025.10.004_bib30","doi-asserted-by":"crossref","first-page":"1980","DOI":"10.1111\/acer.14700","article-title":"A Western diet with alcohol in drinking water recapitulates features of alcohol-associated liver disease in mice","volume":"45","author":"Schonfeld","year":"2021","journal-title":"Alcohol Clin Exp Res"},{"key":"10.1016\/j.ajpath.2025.10.004_bib31","doi-asserted-by":"crossref","DOI":"10.1016\/j.xpro.2021.100363","article-title":"Purification of mouse hepatic non-parenchymal cells or nuclei for use in ChIP-seq and other next-generation sequencing approaches","volume":"2","author":"Troutman","year":"2021","journal-title":"STAR Protoc"},{"key":"10.1016\/j.ajpath.2025.10.004_bib32","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1002\/hep4.1674","article-title":"Arginine methylation of hepatic hnRNPH suppresses complement activation and systemic inflammation in alcohol-fed mice","volume":"5","author":"Schonfeld","year":"2021","journal-title":"Hepatol Commun"},{"key":"10.1016\/j.ajpath.2025.10.004_bib33","doi-asserted-by":"crossref","DOI":"10.1093\/gigascience\/giy083","article-title":"Clustering trees: a visualization for evaluating clusterings at multiple resolutions","volume":"7","author":"Zappia","year":"2018","journal-title":"Gigascience"},{"key":"10.1016\/j.ajpath.2025.10.004_bib34","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1038\/s41590-018-0276-y","article-title":"Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage","volume":"20","author":"Aran","year":"2019","journal-title":"Nat Immunol"},{"key":"10.1016\/j.ajpath.2025.10.004_bib35","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1038\/ni1008-1091","article-title":"The Immunological Genome Project: networks of gene expression in immune cells","volume":"9","author":"Heng","year":"2008","journal-title":"Nat Immunol"},{"key":"10.1016\/j.ajpath.2025.10.004_bib36","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1101\/gr.240093.118","article-title":"Remodeling of epigenome and transcriptome landscapes with aging in mice reveals widespread induction of inflammatory responses","volume":"29","author":"Benayoun","year":"2019","journal-title":"Genome Res"},{"key":"10.1016\/j.ajpath.2025.10.004_bib37","doi-asserted-by":"crossref","first-page":"P3","DOI":"10.1186\/gb-2003-4-5-p3","article-title":"DAVID: database for annotation, visualization, and integrated discovery","volume":"4","author":"Dennis","year":"2003","journal-title":"Genome Biol"},{"key":"10.1016\/j.ajpath.2025.10.004_bib38","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-017-17204-5","article-title":"QuPath: open source software for digital pathology image analysis","volume":"7","author":"Bankhead","year":"2017","journal-title":"Sci Rep"},{"key":"10.1016\/j.ajpath.2025.10.004_bib39","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1038\/ajg.2012.285","article-title":"The interaction of rs738409, obesity, and alcohol: a population-based autopsy study","volume":"107","author":"Dunn","year":"2012","journal-title":"Am J Gastroenterol"},{"key":"10.1016\/j.ajpath.2025.10.004_bib40","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1038\/s41420-017-0020-7","article-title":"FOXO3-dependent apoptosis limits alcohol-induced liver inflammation by promoting infiltrating macrophage differentiation","volume":"4","author":"Li","year":"2018","journal-title":"Cell Death Discov"},{"key":"10.1016\/j.ajpath.2025.10.004_bib41","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1016\/j.immuni.2020.05.014","article-title":"Determinants of resident tissue macrophage identity and function","volume":"52","author":"Bl\u00e9riot","year":"2020","journal-title":"Immunity"},{"key":"10.1016\/j.ajpath.2025.10.004_bib42","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1097\/MOG.0000000000000927","article-title":"Advances in the genetics of nonalcoholic fatty liver disease","volume":"39","author":"Ajmera","year":"2023","journal-title":"Curr Opin Gastroenterol"},{"key":"10.1016\/j.ajpath.2025.10.004_bib43","doi-asserted-by":"crossref","first-page":"4383","DOI":"10.1038\/s41467-018-06318-7","article-title":"Single cell RNA sequencing of human liver reveals distinct intrahepatic macrophage populations","volume":"9","author":"MacParland","year":"2018","journal-title":"Nat Commun"},{"key":"10.1016\/j.ajpath.2025.10.004_bib44","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/j.immuni.2019.09.002","article-title":"Liver-derived signals sequentially reprogram myeloid enhancers to initiate and maintain Kupffer cell identity","volume":"51","author":"Sakai","year":"2019","journal-title":"Immunity"},{"key":"10.1016\/j.ajpath.2025.10.004_bib45","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.cmet.2019.11.013","article-title":"Macrophage MerTK promotes liver fibrosis in nonalcoholic steatohepatitis","volume":"31","author":"Cai","year":"2020","journal-title":"Cell Metab"},{"key":"10.1016\/j.ajpath.2025.10.004_bib46","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1136\/gutjnl-2016-313615","article-title":"MerTK expressing hepatic macrophages promote the resolution of inflammation in acute liver failure","volume":"67","author":"Triantafyllou","year":"2018","journal-title":"Gut"},{"issue":"Suppl","key":"10.1016\/j.ajpath.2025.10.004_bib47","doi-asserted-by":"crossref","first-page":"D20","DOI":"10.1046\/j.1440-1746.2000.02179.x","article-title":"Role of Kupffer cells and gut-derived endotoxins in alcoholic liver injury","volume":"15","author":"Enomoto","year":"2000","journal-title":"J Gastroenterol Hepatol"},{"key":"10.1016\/j.ajpath.2025.10.004_bib48","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1002\/hep.22776","article-title":"An early complement-dependent and TLR-4-independent phase in the pathogenesis of ethanol-induced liver injury in mice","volume":"49","author":"Roychowdhury","year":"2009","journal-title":"Hepatology"}],"container-title":["The American Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002944025004031?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002944025004031?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T23:34:38Z","timestamp":1773876878000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0002944025004031"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":48,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["S0002944025004031"],"URL":"https:\/\/doi.org\/10.1016\/j.ajpath.2025.10.004","relation":{},"ISSN":["0002-9440"],"issn-type":[{"value":"0002-9440","type":"print"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Liver Macrophage Changes during Early Adaptation to Alcohol Exposure","name":"articletitle","label":"Article Title"},{"value":"The American Journal of Pathology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ajpath.2025.10.004","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 American Society for Investigative Pathology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}]}}