{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T03:34:24Z","timestamp":1791516864340,"version":"4.3.4"},"reference-count":32,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2016,12,1]],"date-time":"2016-12-01T00:00:00Z","timestamp":1480550400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2016,12,1]],"date-time":"2016-12-01T00:00:00Z","timestamp":1480550400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Pulm. circ."],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:p>Portopulmonary hypertension (POPH) is a poorly understood complication of liver disease associated with significant morbidity and mortality. We sought to identify novel biomarkers of POPH disease presence and severity. We performed a prospective, multicenter, case\u2010control study involving patients with liver disease undergoing right heart catheterization. POPH cases were defined as a mean pulmonary arterial pressure (mPAP) \u226525\u00a0mmHg and pulmonary vascular resistance (PVR) &gt;240 dynes\u00b7s\u00b7cm<jats:sup>\u22125<\/jats:sup>. Plasma samples were collected from the systemic and pulmonary circulation, and antibody microarray was used to identify biomarkers. Characterization and validation of a candidate cytokine, macrophage migration inhibitory factor (MIF), was performed using enzyme\u2010linked immunosorbent assay. Continuous variables were compared using a Mann\u2010Whitney U test and correlated with disease severity using Spearman correlation. MIF levels were elevated in both the systemic and pulmonary circulation in patients with POPH compared with controls (median MIF level [interquartile range] in systemic circulation: 46.68\u00a0ng\/mL [32.31\u201376.04] vs. 31.19\u00a0ng\/mL [26.92\u201342.17], <jats:italic>P<\/jats:italic> = 0.009; in pulmonary circulation: 49.59\u00a0ng\/mL [35.90\u2013108.80] vs. 37.78 [21.78\u201345.53], <jats:italic>P<\/jats:italic> = 0.002). In patients with POPH, MIF levels were positively correlated with PVR (<jats:italic>r<\/jats:italic> = 0.58, <jats:italic>P<\/jats:italic> = 0.006) and inversely correlated with cardiac output (<jats:italic>r<\/jats:italic> = \u22120.57, <jats:italic>P<\/jats:italic> = 0.007). MIF &gt;60\u00a0ng\/mL or tricuspid regurgitation gradient &gt;50\u00a0mmHg had a 92% sensitivity and specificity for the diagnosis of POPH, with a positive predictive value of 86% and a negative predictive value of 96%. MIF is a promising novel biomarker of POPH disease presence and severity in patients with liver disease and portal hypertension.<\/jats:p>","DOI":"10.1086\/688489","type":"journal-article","created":{"date-parts":[[2016,7,12]],"date-time":"2016-07-12T14:24:00Z","timestamp":1468333440000},"page":"498-507","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":22,"title":["Macrophage Migration Inhibitory Factor as a Novel Biomarker of Portopulmonary Hypertension"],"prefix":"10.1002","volume":"6","author":[{"given":"Hilary M.","family":"DuBrock","sequence":"first","affiliation":[{"name":"Beth Israel Deaconess Medical Center Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josanna M.","family":"Rodriguez\u2010Lopez","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara L.","family":"LeVarge","sequence":"additional","affiliation":[{"name":"Beth Israel Deaconess Medical Center Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Curry","sequence":"additional","affiliation":[{"name":"Beth Israel Deaconess Medical Center Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul A.","family":"VanderLaan","sequence":"additional","affiliation":[{"name":"Beth Israel Deaconess Medical Center Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsuzsanna K.","family":"Zsengeller","sequence":"additional","affiliation":[{"name":"Beth Israel Deaconess Medical Center Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Pernicone","sequence":"additional","affiliation":[{"name":"Beth Israel Deaconess Medical Center Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioana R.","family":"Preston","sequence":"additional","affiliation":[{"name":"Tufts University Medical Center Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul B.","family":"Yu","sequence":"additional","affiliation":[{"name":"Brigham and Women's Hospital Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"Nikolic","sequence":"additional","affiliation":[{"name":"Brigham and Women's Hospital Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dihua","family":"Xu","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravi I.","family":"Thadhani","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard N.","family":"Channick","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Ananth","family":"Karumanchi","sequence":"additional","affiliation":[{"name":"Beth Israel Deaconess Medical Center Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,12]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.10.029"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.09-1140"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21431"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2003.50060"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/lt.500060209"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.11-0160"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1053\/jlts.2000.6356"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.04.00010904"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2013.03.026"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(91)90225-A"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22275"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.06.053"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.4103\/2045-8932.113185"},{"issue":"1","key":"e_1_2_7_15_1","first-page":"235","article-title":"Migration inhibitory factor expression in experimentally induced endotoxemia","volume":"150","author":"Bacher M","year":"1997","journal-title":"Am J Pathol"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201402-0322OC"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.10.032"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.4103\/2045-8932.110445"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.52.9.1355"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1177\/0003319710369101"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/13547500902773896"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.898122"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200809-1472OC"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.159.6.9804054"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1843.2003.00491.x"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/840737"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2012.05.018"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-008-0960-7"},{"issue":"2","key":"e_1_2_7_29_1","first-page":"268","article-title":"Macrophage migration inhibitory factor in systemic lupus erythematosus","volume":"31","author":"Foote A","year":"2004","journal-title":"J Rheumatol"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-011-1951-6"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26664"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.2119\/molmed.2011.00094"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1200"}],"container-title":["Pulmonary Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1086\/688489","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1086\/688489","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1086\/688489","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T06:38:15Z","timestamp":1693204695000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1086\/688489"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,12]]},"references-count":32,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2016,12]]}},"alternative-id":["10.1086\/688489"],"URL":"https:\/\/doi.org\/10.1086\/688489","archive":["Portico"],"relation":{},"ISSN":["2045-8940","2045-8940"],"issn-type":[{"value":"2045-8940","type":"print"},{"value":"2045-8940","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,12]]}}}