{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T21:33:29Z","timestamp":1793309609103,"version":"4.5.0"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","license":[{"start":{"date-parts":[[2022,3,21]],"date-time":"2022-03-21T00:00:00Z","timestamp":1647820800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatol Commun"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Nonalcoholic fatty liver disease (NAFLD) is the most common type of chronic liver disease in children. The mechanisms that drive NAFLD disease progression in this specific patient population remain poorly defined. In this study, we obtained liver biopsy samples from a multiethnic cohort of pediatric patients with NAFLD (n\u00a0=\u00a052, mean age\u00a0=\u00a013.6\u00a0years) and healthy liver controls (n\u00a0=\u00a05). We analyzed transcriptomic changes associated with NAFLD stages using high\u2010throughput RNA sequencing. Unsupervised clustering as well as pairwise transcriptome comparison distinguished NAFLD from healthy livers. We identified perturbations in pathways including calcium and insulin\/glucose signaling occurring early in NAFLD disease, before the presence of histopathologic evidence of advanced disease. Transcriptomic comparisons identified a 25\u2010gene signature associated with the degree of liver fibrosis. We also identified expression of the insulin\u2010like growth factor binding protein (IGFBP) gene family (1\/2\/3\/7) as correlating with disease stages, and it has the potential to be used as a peripheral biomarker in NAFLD. Comparing our data set with publicly available adult and adolescent transcriptomic data, we identified similarities and differences in pathway enrichment and gene\u2010expression profiles between adult and pediatric patients with NAFLD. Regulation of genes including interleukin\u201032, IGFBP1, IGFBP2, and IGFBP7 was consistently found in both NAFLD populations, whereas IGFBP3 was specific to pediatric NAFLD. <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic> This paper expands our knowledge on the molecular mechanisms underlying pediatric NAFLD. It identifies potential biomarkers and directs us toward new therapies in this population.<\/jats:p>","DOI":"10.1002\/hep4.1940","type":"journal-article","created":{"date-parts":[[2022,3,21]],"date-time":"2022-03-21T10:23:42Z","timestamp":1647858222000},"page":"1598-1610","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":27,"title":["Transcriptomic profiling of a multiethnic pediatric NAFLD cohort reveals genes and pathways associated with disease"],"prefix":"10.1097","volume":"6","author":[{"given":"Kangning","family":"Yao","sequence":"first","affiliation":[{"name":"Department of Pediatrics,Yale University,New Haven,Connecticut,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Tarabra","sequence":"additional","affiliation":[{"name":"Department of Pediatrics,Yale University,New Haven,Connecticut,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Sia","sequence":"additional","affiliation":[{"name":"Division of Liver Diseases,Department of Medicine,Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai,New York,New York,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaella","family":"Morotti","sequence":"additional","affiliation":[{"name":"Department of Pathology,Yale University,New Haven,Connecticut,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rima","family":"Fawaz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics,Yale University,New Haven,Connecticut,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8227-2004","authenticated-orcid":false,"given":"Pamela","family":"Valentino","sequence":"additional","affiliation":[{"name":"Department of Pediatrics,Yale University,New Haven,Connecticut,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Santoro","sequence":"additional","affiliation":[{"name":"Department of Pediatrics,Yale University,New Haven,Connecticut,USA"},{"name":"Department of Medicine and Health Sciences,\u201cV. Tiberio,\u201d University of Molise,Campobasso,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Caprio","sequence":"additional","affiliation":[{"name":"Department of Pediatrics,Yale University,New Haven,Connecticut,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology,School of Medicine,Pittsburgh Liver Research Center,University of Pittsburgh,University of Pittsburgh Medical Center,Pittsburgh,Pennsylvania,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7936-7168","authenticated-orcid":false,"given":"Dean","family":"Yimlamai","sequence":"additional","affiliation":[{"name":"Department of Pediatrics,Yale University,New 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