{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T13:35:35Z","timestamp":1765546535310,"version":"3.40.5"},"reference-count":51,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","license":[{"start":{"date-parts":[[2019,10,30]],"date-time":"2019-10-30T00:00:00Z","timestamp":1572393600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hepatol Commun"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:p>Severe alcoholic hepatitis (SAH) has high mortality. Dysregulated lipid transport and metabolism in liver\/macrophages contributes to disease pathophysiology. Paraoxonase\/arylesterase 1 (PON1), a liver\u2010specific enzyme, inhibits oxidation of phospholipids and prevents lipid\u2010mediated oxidative damage. However, its functional contribution in macrophage\u2010mediated hepatic injury warrants elucidation. Plasma proteome of patients with SAH (n\u00a0=\u00a020), alcoholic cirrhosis (n\u00a0=\u00a020), and healthy controls was analyzed. Dysregulated pathways were identified, validated, and correlated with severity and outcomes in 200 patients with SAH. Tohoku\u2010Hospital\u2010Pediatrics\u20101 (THP1)\u2010derived macrophages were treated with plasma from study groups in the presence\/absence of recombinant PON1 and the phenotype; intracellular lipid bodies and linked functions were evaluated. In patients with SAH, 208 proteins were &gt;1.5 fold differentially regulated (32 up\u2010regulated and 176 down\u2010regulated; <jats:italic toggle=\"yes\">P\u00a0&lt;<\/jats:italic>\u00a00.01).Validation studies confirmed lower levels of lipid transporter proteins (Pon1, apolipoprotein [Apo]B, ApoA1, ApoA2, and ApoC3; <jats:italic toggle=\"yes\">P\u00a0&lt;<\/jats:italic>\u00a00.01). Low PON1 levels inversely correlated with severity and mortality (r<jats:sup>2<\/jats:sup>\u00a0&gt;\u00a00.3; hazard ratio, 0.91; <jats:italic toggle=\"yes\">P\u00a0&lt;<\/jats:italic>\u00a00.01) and predicted nonsurvivors (area under the receiver operating characteristic curve, 0.86; cut\u2010off, &lt;18\u00a0\u03bcg\/mL; log rank, &lt;0.01). Low PON1 levels corroborated with increased oxidized low\u2010density lipoprotein levels, intracellular lipid bodies, lipid uptake, lipid metabolism, biosynthesis, and alternative macrophage activation genes in nonsurvivors (<jats:italic toggle=\"yes\">P\u00a0&lt;<\/jats:italic>\u00a00.01). Importantly, <jats:italic toggle=\"yes\">in vitro<\/jats:italic> recombinant PON1 treatment on THP1 macrophages reversed these changes (<jats:italic toggle=\"yes\">P\u00a0&lt;<\/jats:italic>\u00a00.01), specifically by alteration in expression of clusters of differentiation 36 (CD36) and adenosine triphosphate\u2010binding cassette subfamily A1 (ABCA1) receptor on macrophages. <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic> Lipid transport proteins contribute to the pathogenesis of SAH, and low PON1 levels inversely correlate with the severity of alcoholic hepatitis and 28\u2010day mortality. Restitution of circulating PON1 may be beneficial and needs therapeutic evaluation in patients with SAH.<\/jats:p>","DOI":"10.1002\/hep4.1438","type":"journal-article","created":{"date-parts":[[2019,10,31]],"date-time":"2019-10-31T06:14:41Z","timestamp":1572502481000},"page":"1598-1625","source":"Crossref","is-referenced-by-count":6,"title":["Dysregulated Lipid Transport Proteins Correlate With Pathogenesis and Outcome in Severe Alcoholic Hepatitis"],"prefix":"10.1097","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3938-362X","authenticated-orcid":false,"given":"Jaswinder Singh","family":"Maras","sequence":"first","affiliation":[{"name":"Department of Research,Institute of Liver and Biliary Sciences,New Delhi,India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sukanta","family":"Das","sequence":"additional","affiliation":[{"name":"Department of Research,Institute of Liver and Biliary Sciences,New Delhi,India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adil","family":"Bhat","sequence":"additional","affiliation":[{"name":"Department of Research,Institute of Liver and Biliary Sciences,New Delhi,India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashish","family":"Kumar Vyas","sequence":"additional","affiliation":[{"name":"Department of Research,Institute of Liver and Biliary Sciences,New Delhi,India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gaurav","family":"Yadav","sequence":"additional","affiliation":[{"name":"Department of Research,Institute of Liver and Biliary Sciences,New Delhi,India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sudrishti","family":"Chaudhary","sequence":"additional","affiliation":[{"name":"Department of Research,Institute of Liver and Biliary Sciences,New Delhi,India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sukriti","family":"Sukriti","sequence":"additional","affiliation":[{"name":"Department of Research,Institute of Liver and Biliary Sciences,New Delhi,India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abhishak C.","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Research,Institute of Liver and Biliary Sciences,New Delhi,India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chagan","family":"Bihari","sequence":"additional","affiliation":[{"name":"Department of Hepatology,Institute of Liver and Biliary Sciences,New Delhi,India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rakhi","family":"Mahiwall","sequence":"additional","affiliation":[{"name":"Department of Pathology,Institute of Liver and Biliary Sciences,New 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