{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:49:00Z","timestamp":1785419340747,"version":"3.56.0"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T00:00:00Z","timestamp":1710288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018952","name":"Birmingham Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100018952","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Alcohol-related liver disease (ARLD) accounts for over one third of all deaths from liver conditions, and mortality from alcohol-related liver disease has increased nearly five-fold over the last 30 years. Severe alcohol-related hepatitis almost always occurs in patients with a background of chronic liver disease with extensive fibrosis or cirrhosis, can precipitate \u2018acute on chronic\u2019 liver failure and has a high short-term mortality. Patients with alcohol-related liver\u00a0disease have impaired immune responses, and increased susceptibility to infections, thus prompt diagnosis of infection and careful patient management is required. The identification of early and non-invasive diagnostic and prognostic biomarkers in ARLD remains an unresolved challenge. Easily calculated predictors of infection and mortality are required for use in patients who often exhibit variable symptoms and disease severity and may not always present in a specialized gastroenterology unit.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We have used a simple haematological analyser to rapidly measure circulating myeloid cell parameters across the ARLD spectrum.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results and Discussion<\/jats:title><jats:p>We demonstrate for the first time that immature granulocyte (IG) counts correlate with markers of disease severity, and our data suggests that elevated counts are associated with increased short-term mortality and risk of infection. Other myeloid populations such as eosinophils and basophils also show promise. Thus IG count has the potential to serve alongside established markers such as neutrophil: lymphocyte ratio as a simply calculated predictor of mortality and risk of infectious complications in patients with alcohol-related hepatitis. This would allow identification of patients who may require more intensive management.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1330536","type":"journal-article","created":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T04:33:11Z","timestamp":1710304391000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Circulating myeloid populations have prognostic utility in alcohol-related liver disease"],"prefix":"10.3389","volume":"15","author":[{"given":"Reenam","family":"Khan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shees","family":"Salman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Harford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lozan","family":"Sheriff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon","family":"Hazeldine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Rajoriya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip N.","family":"Newsome","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia F.","family":"Lalor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,3,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.03.017","article-title":"Global burden of liver disease: 2023 update","volume":"79","author":"Devarbhavi","year":"2023","journal-title":"J Hepatol"},{"key":"B2","volume-title":"Deaths from Liver Disease: Implications for End of Life Care in England","year":"2012"},{"key":"B3","volume-title":"Calling time \u2013 The nation\u2019s drinking as a major health issue","year":"2004"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(95)91685-7","article-title":"Determinants of progression to cirrhosis or fibrosis in pure alcoholic fatty liver","volume":"346","author":"Teli","year":"1995","journal-title":"Lancet"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1111\/apt.16461","article-title":"Alcohol-associated liver disease in the United States is associated with severe forms of disease among young, females and Hispanics","volume":"54","author":"Singal","year":"2021","journal-title":"Aliment Pharmacol Ther"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2018.12.008","article-title":"Acute-on-chronic liver failure in patients with alcohol-related liver disease","volume":"70","author":"Gustot","year":"2019","journal-title":"J Hepatol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2009.189639","article-title":"Early features of acute-on-chronic alcoholic liver failure: a prospective cohort study","volume":"59","author":"Katoonizadeh","year":"2010","journal-title":"Gut"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.04.062","article-title":"Infection in patients with severe alcoholic hepatitis treated with steroids: early response to therapy is the key factor","volume":"137","author":"Louvet","year":"2009","journal-title":"Gastroenterology"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jceh.2021.12.010","article-title":"Alcohol and acute-on-chronic liver failure","volume":"12","author":"Ballester","year":"2022","journal-title":"J Clin Exp Hepatol"},{"key":"B10","doi-asserted-by":"publisher","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 Hepatol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1111\/liv.15701","article-title":"Management of alcoholic hepatitis: A clinical perspective","volume":"43","author":"Kasper","year":"2023","journal-title":"Liver Int"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2016.02.042","article-title":"Standard definitions and common data elements for clinical trials in patients with alcoholic hepatitis: recommendation from the NIAAA alcoholic hepatitis consortia","volume":"150","author":"Crabb","year":"2016","journal-title":"Gastroenterology"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.11.012","article-title":"The CLIF Consortium Acute Decompensation score (CLIF-C ADs) for prognosis of hospitalised cirrhotic patients without acute-on-chronic liver failure","volume":"62","author":"Jalan","year":"2015","journal-title":"J Hepatol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.971346","article-title":"Myeloid cells in alcoholic liver diseases: Mechanism and prospect","volume":"13","author":"Xu","year":"2022","journal-title":"Front Immunol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-021-07140-w","article-title":"Determinants of short- and long-term outcomes of an Australian cohort of patients admitted with alcoholic hepatitis","volume":"67","author":"Vaz","year":"2022","journal-title":"Dig Dis Sci"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1111\/apt.15335","article-title":"Baseline neutrophil-to-lymphocyte ratio predicts response to corticosteroids and is associated with infection and renal dysfunction in alcoholic hepatitis","volume":"50","author":"Forrest","year":"2019","journal-title":"Aliment Pharmacol Ther"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30249","article-title":"Pharmacological inhibition of CCR2\/5 signaling prevents and reverses alcohol-induced liver damage, steatosis, and inflammation in mice","volume":"69","author":"Ambade","year":"2019","journal-title":"Hepatology"},{"key":"B18","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1186\/s13054-015-0778-z","article-title":"The diagnostic and prognostic significance of monitoring blood levels of immature neutrophils in patients with systemic inflammation","volume":"19","author":"Mare","year":"2015","journal-title":"Crit Care"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12222","article-title":"Impaired neutrophil extracellular trap formation: a novel defect in the innate immune system of aged individuals","volume":"13","author":"Hazeldine","year":"2014","journal-title":"Aging Cell"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1002\/(ISSN)1527-3350","article-title":"Development of a simple noninvasive index to predict significant fibrosis in patients with HIV\/HCV coinfection","volume":"43","author":"Sterling","year":"2006","journal-title":"Hepatology"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1002\/jgh3.12707","article-title":"Elevated blood monocyte counts in alcohol-associated hepatitis","volume":"6","author":"Voss","year":"2022","journal-title":"JGH Open"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1515\/cclm-2012-0147","article-title":"Evaluation of the immature myeloid information (IMI) by Sysmex XE 2100(R) hematology analyzer in the identification of blasts of myeloid lineage","volume":"50","author":"Farias","year":"2012","journal-title":"Clin Chem Lab Med"},{"key":"B23","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1038\/s41598-021-04682-x","article-title":"Dysfunction of low-density neutrophils in peripheral circulation in patients with sepsis","volume":"12","author":"Sun","year":"2022","journal-title":"Sci Rep"},{"key":"B24","doi-asserted-by":"publisher","first-page":"3902","DOI":"10.1016\/j.celrep.2019.05.091","article-title":"Immature low-density neutrophils exhibit metabolic flexibility that facilitates breast\u00a0cancer liver metastasis","volume":"27","author":"Hsu","year":"2019","journal-title":"Cell Rep"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0b013e318173ef9c","article-title":"Immature circulating neutrophils in sepsis have impaired phagocytosis and calcium signaling","volume":"30","author":"Taneja","year":"2008","journal-title":"Shock"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0000000000001807","article-title":"Immature granulocytes, and cell-free DNA are early biomarkers of sepsis in burn-injured patients: A prospective observational cohort study","volume":"265","author":"Hampson","year":"2017","journal-title":"Ann Surg"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1412278","article-title":"Prednisolone or pentoxifylline for alcoholic hepatitis","volume":"372","author":"Thursz","year":"2015","journal-title":"N Engl J Med"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20041419","article-title":"Inflammation and the reciprocal production of granulocytes and lymphocytes in bone marrow","volume":"201","author":"Ueda","year":"2005","journal-title":"J Exp Med"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1111\/liv.12688","article-title":"Neutrophil-to-lymphocyte ratio predicts mortality in patients listed for liver transplantation","volume":"35","author":"Leithead","year":"2015","journal-title":"Liver Int"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S372666","article-title":"Diagnostic and prognostic value of monocyte distribution width in sepsis","volume":"15","author":"Wu","year":"2022","journal-title":"J Inflammation Res"},{"key":"B31","doi-asserted-by":"publisher","first-page":"2332","DOI":"10.3390\/cells10092332","article-title":"Reactivity and granularity research parameters to characterize and differentiate convalescent patients from active SARS-coV-2 infection","volume":"10","author":"Kwiecien","year":"2021","journal-title":"Cells"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1002\/(ISSN)1097-0320","article-title":"Flow cytometric method for enumeration and classification of reactive immature granulocyte populations","volume":"42","author":"Fujimoto","year":"2000","journal-title":"Cytometry"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1093\/icvts\/ivy360","article-title":"Immature granulocytes as a sepsis predictor in patients undergoing cardiac surgery","volume":"28","author":"Porizka","year":"2019","journal-title":"Interact Cardiovasc Thorac Surg"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2017.05.014","article-title":"Evaluation of lactate, white blood cell count, neutrophil count, procalcitonin and immature granulocyte count as biomarkers for sepsis in emergency department patients","volume":"50","author":"Karon","year":"2017","journal-title":"Clin Biochem"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1111\/ijlh.12990","article-title":"Immature granulocytes index as early marker of sepsis","volume":"41","author":"Ayres","year":"2019","journal-title":"Int J Lab Hematol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1309\/LT30BV9UJJV9CFHQ","article-title":"Immature granulocyte measurement using the Sysmex XE-2100","volume":"120","author":"Ansari-Lari","year":"2003","journal-title":"Relationship to infection sepsis. Am J Clin Pathol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-023-01490-5","article-title":"Neutrophils and emergency granulopoiesis drive immune suppression and an extreme response endotype during sepsis","volume":"24","author":"Kwok","year":"2023","journal-title":"Nat Immunol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1007\/BF00308740","article-title":"The increase of low density subpopulations and CD10 (CALLA) negative neutrophils in severely infected patients","volume":"22","author":"Morisaki","year":"1992","journal-title":"Surg Today"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s12308-022-00484-w","article-title":"Evaluation of immature granulocyte parameters in myeloid neoplasms assayed by Sysmex XN hematology analyzer","volume":"15","author":"Lu","year":"2022","journal-title":"J Hematop"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.672520","article-title":"Low-density neutrophils in healthy individuals display a mature primed phenotype","volume":"12","author":"Blanco-Camarillo","year":"2021","journal-title":"Front Immunol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"e122311","DOI":"10.1172\/jci.insight.122311","article-title":"Mature neutrophils suppress T cell immunity in ovarian cancer microenvironment","volume":"4","author":"Singel","year":"2019","journal-title":"JCI Insight"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.04.004","article-title":"MDSC: Markers, development, states, and unaddressed complexity","volume":"54","author":"Hegde","year":"2021","journal-title":"Immunity"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2010.11.034","article-title":"Evidence of neutrophil functional defect despite inflammation in stable cirrhosis","volume":"55","author":"Tritto","year":"2011","journal-title":"J Hepatol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1002\/(ISSN)1527-3350","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"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1080\/15504263.2022.2090650","article-title":"Eosinophils to lymphocytes ratio (ELR) as a potential inflammatory biomarker in patients with dual diagnosis of bipolar and alcohol use disorders: A retrospective cohort study","volume":"18","author":"Dirani","year":"2022","journal-title":"J Dual Diagn"},{"key":"B46","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1111\/j.1398-9995.2004.00469.x","article-title":"Cytokine-regulated accumulation of eosinophils in inflammatory disease","volume":"59","author":"Lampinen","year":"2004","journal-title":"Allergy"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2022.02.024","article-title":"Hepatic recruitment of eosinophils and their protective function during acute liver injury","volume":"77","author":"Xu","year":"2022","journal-title":"J\u00a0Hepatol"},{"key":"B48","doi-asserted-by":"publisher","first-page":"2554","DOI":"10.3390\/cells11162554","article-title":"The usefulness of extended inflammation parameters and systemic inflammatory response markers in the diagnostics of autoimmune hepatitis","volume":"11","author":"Domerecka","year":"2022","journal-title":"Cells"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(00)80219-6","article-title":"Blood neutrophil functions and cytokine release in severe alcoholic hepatitis: effect of corticosteroids","volume":"32","author":"Taieb","year":"2000","journal-title":"J Hepatol"},{"key":"B50","doi-asserted-by":"publisher","first-page":"100871","DOI":"10.1016\/j.jhepr.2023.100871","article-title":"Circulating neutrophil anti-pathogen dysfunction in cirrhosis","volume":"5","author":"Balazs","year":"2023","journal-title":"JHEP Rep"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1086\/315742","article-title":"In vivo neutrophil dysfunction in cirrhotic patients with advanced liver disease","volume":"182","author":"Fiuza","year":"2000","journal-title":"J Infect Dis"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1111\/sji.12714","article-title":"Impaired neutrophil extracellular traps and inflammatory responses in the peritoneal fluid of patients with liver cirrhosis","volume":"88","author":"Agraz-Cibrian","year":"2018","journal-title":"Scand J Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1330536\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T04:33:16Z","timestamp":1710304396000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1330536\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,13]]},"references-count":52,"alternative-id":["10.3389\/fimmu.2024.1330536"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2024.1330536","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,13]]},"article-number":"1330536"}}