{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:50:59Z","timestamp":1790700659982,"version":"4.1.0"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","license":[{"start":{"date-parts":[[2018,9,21]],"date-time":"2018-09-21T00:00:00Z","timestamp":1537488000000},"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":["Hepatology Communications"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:p>\n                    The severity of hepatic fibrosis is the primary predictor of liver\u2010related morbidity and mortality in patients with nonalcoholic fatty liver disease (NAFLD). Unfortunately, noninvasive serum biomarkers for NAFLD\u2010associated fibrosis are limited. We analyzed baseline serum samples for 24 cytokines of 97 patients with biopsy\u2010proven NAFLD. These patients were prospectively enrolled in a clinical study (ClinicalTrials.gov NCT00794716) to identify cytokines associated with liver fibrosis in patients with nonalcoholic steatohepatitis. Patients were stratified according to severity of hepatic fibrosis (mild, stage 0\u20101, n\u00a0=\u00a037; moderate, stage 2, n\u00a0=\u00a040; and advanced, stage 3\u20104, n\u00a0=\u00a020) while controlling for age, race, sex, body mass index, and diabetes mellitus. Interleukin\u20108 (IL\u20108), osteopontin (OPN), and monocyte chemoattractant protein 1 (MCP1) were associated with liver fibrosis (\n                    <jats:italic toggle=\"yes\">P &lt;<\/jats:italic>\n                    \u00a00.001,\n                    <jats:italic toggle=\"yes\">P =<\/jats:italic>\n                    \u00a00.005,\n                    <jats:italic toggle=\"yes\">P =<\/jats:italic>\n                    \u00a00.016, respectively). After controlling for steatosis, lobular inflammation, hepatocyte ballooning, age, sex, body mass index, diabetes mellitus, hypertension, and metabolic syndrome status, IL\u20108 remained strongly associated with fibrosis (\n                    <jats:italic toggle=\"yes\">P =<\/jats:italic>\n                    \u00a00.001). Furthermore, IL\u20108 was also a strong predictor of increased fibrotic liver injury compared to established markers of hepatic fibrosis. Hepatic gene expression from 72 patients with NAFLD (n\u00a0=\u00a040 mild fibrosis; n\u00a0=\u00a032 advanced fibrosis) from the Duke University Health System NAFLD Clinical Database and Biorepository revealed IL\u20108, MCP1, and OPN gene expression to be increased and differentially expressed in patients with advanced hepatic fibrosis. Thus, serum IL\u20108, MCP1, and OPN may reflect up\u2010regulated gene expression during liver fibrosis in NAFLD.\n                    <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic>\n                    Serum IL\u20108, MCP1, and OPN may serve as a test for advanced hepatic fibrosis in NAFLD and thus reveal novel targets for antifibrotic therapies. The increased serum IL\u20108, MCP1, and OPN that correspond with associated hepatic gene expression lend strength to such analytes as ideal surrogate serum biomarkers for severity of hepatic fibrosis.\n                  <\/jats:p>","DOI":"10.1002\/hep4.1237","type":"journal-article","created":{"date-parts":[[2018,9,22]],"date-time":"2018-09-22T05:03:55Z","timestamp":1537592635000},"page":"1344-1355","source":"Crossref","is-referenced-by-count":98,"title":["Serum Interleukin\u20108, Osteopontin, and Monocyte Chemoattractant Protein 1 Are Associated With Hepatic Fibrosis in Patients With Nonalcoholic Fatty Liver Disease"],"prefix":"10.1097","volume":"2","author":[{"given":"Oliver","family":"Glass","sequence":"first","affiliation":[{"name":"Division of General Internal Medicine,Duke University,Durham,NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Henao","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics,Duke University,Durham,NC"},{"name":"Duke Clinical Research Institute,Duke University,Durham,NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keyur","family":"Patel","sequence":"additional","affiliation":[{"name":"University Health Network,University of Toronto,Toronto,Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia D.","family":"Guy","sequence":"additional","affiliation":[{"name":"Department of Pathology,Duke University,Durham,NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans J.","family":"Gruss","sequence":"additional","affiliation":[{"name":"Norgine, Ltd.,Uxbridge,United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wing\u2010Kin","family":"Syn","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Medical University of South Carolina,Charleston,SC"},{"name":"Section of Gastroenterology,Ralph H Johnson Veterans Affairs Medical Center,Charleston,SC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia A.","family":"Moylan","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Streilein","sequence":"additional","affiliation":[{"name":"Department of Dermatology,Duke University,Durham,NC."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell","family":"Hall","sequence":"additional","affiliation":[{"name":"Department of Dermatology,Duke University,Durham,NC."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Mae Diehl","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manal F.","family":"Abdelmalek","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and 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