{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T03:34:58Z","timestamp":1789443298044,"version":"build-2803163510"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":175,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology , Ministry of Science and Technology","doi-asserted-by":"publisher","award":["BT\/PR14094\/MED\/30\/372\/2010"],"award-info":[{"award-number":["BT\/PR14094\/MED\/30\/372\/2010"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2015,4]]},"abstract":"<jats:p>\n                    Acute\u2010on\u2010chronic liver failure (ACLF) is an ailment with high incidence of multiorgan failure (MOF) and consequent mortality. Dysregulated iron homeostasis and macrophage dysfunction are linked to increased incidence of MOF. We investigated whether a panel of circulating iron\u2010regulating proteins are associated with development of MOF and can predict 15\u2010 or 30\u2010day mortality in ACLF patients. One hundred twenty patients with ACLF, 20 patients with compensated cirrhosis, and 20 healthy controls were studied. Relative protein expression profiling was performed in the derivative cohort and confirmed in the validation cohort. A panel of iron regulators and indices were determined. Multiparametric flow cytometry for quantitation of labile iron pool (LIP) was performed. Validation studies confirmed lower serum transferrin (Tf) and ceruloplasmin levels in ACLF and ACLF\u2010MOF, compared to patients with cirrhosis and controls (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u2009&lt;\u20090.01). Serum iron and ferritin levels were markedly elevated (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u2009&lt;\u20090.001;\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u2009&lt;\u20090.05) and hepcidin levels were lower (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u2009&lt;\u20090.001) in ACLF patients with MOF than those without and other groups (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u2009&lt;\u20090.001). Percentage Tf saturation (%SAT) was higher in ACLF\u2010MOF (39.2%;\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u2009&lt;\u20090.001) and correlated with poor outcome (hazard ratio: 6.970;\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u2009&lt;\u20090.01). Intracellular LIP indices were significantly elevated in the subsets of circulating macrophages in ACLF\u2010MOF, compared to other groups (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u2009&lt;\u20090.01). Whereas expression of iron\u2010regulatory genes was markedly down\u2010regulated, genes related to endoplasmic reticulum stress, apoptosis, and inflammation were up\u2010regulated in ACLF patients, compared to patients with cirrhosis. Severe dysregulation of autophagy mechanisms was also observed in the former.\n                    <jats:italic toggle=\"yes\">Conclusions<\/jats:italic>\n                    : Iron metabolism and transport are severely deranged in ACLF patients and more so in those with MOF. %SAT, circulating hepcidin, and LIP in macrophages correlate with disease severity and %SAT could be used for early prognostication in ACLF patients. (H\n                    <jats:sc>epatology<\/jats:sc>\n                    2015;61:1306\u20131320)\n                  <\/jats:p>","DOI":"10.1002\/hep.27636","type":"journal-article","created":{"date-parts":[[2014,12,8]],"date-time":"2014-12-08T19:20:10Z","timestamp":1418066410000},"page":"1306-1320","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":76,"title":["Dysregulated iron homeostasis is strongly associated with multiorgan failure and early mortality in acute\u2010on\u2010chronic liver failure"],"prefix":"10.1097","volume":"61","author":[{"given":"Jaswinder Singh","family":"Maras","sequence":"first","affiliation":[{"name":"Departments of Research,Institute of Liver & Biliary Sciences (ILBS),New Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rakhi","family":"Maiwall","sequence":"additional","affiliation":[{"name":"Hepatology,Institute of Liver & Biliary Sciences (ILBS),New Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.C.","family":"Harsha","sequence":"additional","affiliation":[{"name":"Institute of Bioinformatics,International Technology Park,Bangalore,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sukanta","family":"Das","sequence":"additional","affiliation":[{"name":"Departments of Research,Institute of Liver & Biliary Sciences (ILBS),New Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md.Shabir","family":"Hussain","sequence":"additional","affiliation":[{"name":"Departments of Research,Institute of Liver & Biliary Sciences (ILBS),New Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandan","family":"Kumar","sequence":"additional","affiliation":[{"name":"Hepatology,Institute of Liver & Biliary Sciences (ILBS),New Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chhagan","family":"Bihari","sequence":"additional","affiliation":[{"name":"Department of Pathology,ILBS,New Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Archana","family":"Rastogi","sequence":"additional","affiliation":[{"name":"Department of Pathology,ILBS,New Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manoj","family":"Kumar","sequence":"additional","affiliation":[{"name":"Hepatology,Institute of Liver & Biliary Sciences (ILBS),New Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nirupama","family":"Trehanpati","sequence":"additional","affiliation":[{"name":"Departments of Research,Institute of Liver & Biliary Sciences (ILBS),New Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shvetank","family":"Sharma","sequence":"additional","affiliation":[{"name":"Departments of Research,Institute of Liver & Biliary Sciences (ILBS),New Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akhilesh","family":"Pandey","sequence":"additional","affiliation":[{"name":"Institute of Bioinformatics,International Technology Park,Bangalore,India"},{"name":"Departments of Biological Chemistry,Johns Hopkins University School of Medicine,Baltimore,MD"},{"name":"Pathology,Johns Hopkins University School of Medicine,Baltimore,MD"},{"name":"Oncology, McKusick\u2010Nathans Institute of Genetic Medicine,Johns Hopkins University School of Medicine,Baltimore,MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiv Kumar","family":"Sarin","sequence":"additional","affiliation":[{"name":"Departments of Research,Institute of Liver & Biliary Sciences (ILBS),New Delhi,India"},{"name":"Hepatology,Institute of Liver & Biliary Sciences (ILBS),New Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2015,3,10]]},"reference":[{"key":"hep27636-bib-0001-20241017","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1159\/000047017","article-title":"Acute\u2010on\u2010chronic liver failure: pathophysiological basis of therapeutic options","volume":"20","year":"2002","journal-title":"Blood Purif"},{"key":"hep27636-bib-0002-20241017","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1586\/egh.11.47","article-title":"Acute\u2010on\u2010chronic liver failure: current concepts on definition, pathogenesis, clinical manifestations and potential therapeutic interventions","volume":"5","year":"2011","journal-title":"Expert Rev Gastroenterol Hepatol"},{"key":"hep27636-bib-0003-20241017","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/s12072-008-9106-x","article-title":"Acute\u2010on\u2010chronic liver failure: consensus recommendations of the Asian 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History"}},{"value":"2014-11-20","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}