{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:22:08Z","timestamp":1760142128147,"version":"build-2065373602"},"reference-count":30,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,8,3]],"date-time":"2025-08-03T00:00:00Z","timestamp":1754179200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Acute\u2010on\u2010chronic liver failure (ACLF) is associated with immune dysregulation, characterized by simultaneous inflammation and immune suppression. Alcohol\u2010related ACLF (A\u2010ACLF) has particularly high mortality, yet the role of monocyte dysfunction and plasma\u2010derived inflammatory mediators remains poorly understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A prospective study was conducted from July 2019 to May 2020, recruiting A\u2010ACLF patients and healthy controls. Monocyte phenotyping and serum immune markers (sCD163, sCD25, ferritin, and IgG immune complexes) were measured. Ex\u00a0vivo plasma priming experiments were performed on healthy monocytes, and cytokine production was measured.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A\u2010ACLF patients (<jats:italic>n<\/jats:italic>\u2009=\u200925, median [min\u2013max] age: 42 [23\u201364] years, 24 males) showed higher proportions (12.5 [3.47\u201341.8] vs. 2.98 [0.62\u20138.89]) and counts of monocytes (counts\/\u03bcL: 229 [48\u20131505] vs. 82 [22\u2013250]), with increased classical and reduced patrolling monocyte subsets correlating with higher MELD scores (<jats:italic>r<\/jats:italic>\u2009=\u20090.48, <jats:italic>p<\/jats:italic>\u2009=\u20090.05) and poor outcomes. A\u2010ACLF monocytes showed increased Fc receptor expression (CD64 MFI: 4648 [2214\u20137819] vs. 1834 [168\u20133221]), suggesting monocyte hyperactivation and responsiveness to immune complexes, and lower HLA\u2010DR expression (MFI 444 [133\u20131147] vs. 916 [451\u20132067]), indicating immune exhaustion. Increased expression of the liver\u2010homing receptor CCR2 was noted in classical monocytes. Healthy human peripheral monocytes cultured with A\u2010ACLF plasma showed upregulated CCR5 and downregulated CD14, suggesting effects on monocyte trafficking and differentiation. Monocytes primed with A\u2010ACLF plasma secreted higher TNF\u2010\u03b1, IL\u20101\u03b2, IL\u201012, and G\u2010CSF, indicating plasma\u2010driven inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings reveal monocyte dysfunction and plasma\u2010induced immune alterations as key contributors to A\u2010ACLF pathogenesis and prognosis. Targeting plasma\u2010derived inflammatory mediators may offer novel therapeutic strategies.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jgh.70053","type":"journal-article","created":{"date-parts":[[2025,8,3]],"date-time":"2025-08-03T23:26:16Z","timestamp":1754263576000},"page":"2591-2600","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Plasma\u2010Driven Monocyte Dysfunction Drives Disease Progression in Alcohol\u2010Related Acute\u2010on\u2010Chronic Liver Failure"],"prefix":"10.1111","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9398-4958","authenticated-orcid":false,"given":"B.","family":"Vijayalekshmi","sequence":"first","affiliation":[{"name":"Wellcome Trust Research Laboratory, Division of Gastrointestinal Sciences Christian Medical College  Vellore Tamil Nadu India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anita","family":"Chaudhary","sequence":"additional","affiliation":[{"name":"Wellcome Trust Research Laboratory, Division of Gastrointestinal Sciences Christian Medical College  Vellore Tamil Nadu India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Savit\u00a0B.","family":"Prabhu","sequence":"additional","affiliation":[{"name":"Wellcome Trust Research Laboratory, Division of Gastrointestinal Sciences Christian Medical College  Vellore Tamil Nadu India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anand","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Hepatology Christian Medical College  Vellore Tamil Nadu India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.\u00a0A.","family":"Balasubramanian","sequence":"additional","affiliation":[{"name":"Wellcome Trust Research Laboratory, Division of Gastrointestinal Sciences Christian Medical College  Vellore Tamil Nadu India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uday","family":"Zachariah","sequence":"additional","affiliation":[{"name":"Department of Hepatology Christian Medical College  Vellore Tamil Nadu India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5833-2839","authenticated-orcid":false,"given":"C.\u00a0E.","family":"Eapen","sequence":"additional","affiliation":[{"name":"Department of Hepatology Christian Medical College  Vellore Tamil Nadu India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashish","family":"Goel","sequence":"additional","affiliation":[{"name":"Department of Hepatology Christian Medical College  Vellore Tamil Nadu India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,8,3]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2012.06.026"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.13340"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.752875"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.02013"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12664-018-0827-z"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00476"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28740"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0096864"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.09.002"},{"issue":"2","key":"e_1_2_11_11_1","first-page":"148","article-title":"Elevated Blood Monocyte Counts in Alcohol\u2010Associated Hepatitis","volume":"6","author":"Voss J. 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