{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T04:08:52Z","timestamp":1791086932937,"version":"4.1.0"},"reference-count":57,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":4445,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2003,7]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>Although the molecular basis for the pathophysiology of nonalcoholic steatohepatitis (NASH) is poorly understood, insulin resistance and mitochondrial dysfunction are physiologic hallmarks of this condition. We sought evidence of a transcriptional or pretranscriptional basis for insulin resistance and mitochondrial dysfunction through measurement of hepatic gene expression (messenger RNA [mRNA]) using high\u2013density synthetic oligonucleotide microarray analysis (Hu6800 GeneChip, Affymetrix, CA). Global hepatic gene expression was determined in snap\u2013frozen liver biopsy specimens from 4 groups: (1) patients with cirrhotic\u2013stage NASH (n = 6), (2) patients with cirrhosis caused by hepatitis C virus (HCV) (n = 6), (3) patients with cirrhosis secondary to primary biliary cirrhosis (PBC) (n = 6), and (4) healthy controls (n = 6). Genes were considered to be expressed differentially in NASH only if there was a greater than 2\u2013fold difference in abundance of mRNA when compared with each of the control groups. Sixteen genes were uniquely differentially expressed (4 overexpressed and 12 underexpressed) in patients with cirrhotic\u2013stage NASH. Genes that were significantly underexpressed included genes important for maintaining mitochondrial function (copper\/zinc superoxide dismutase, aldehyde oxidase, and catalase). Glucose 6\u2013phospatase, alcohol dehydrogenase, elongation factor\u2013TU, methylglutaryl coenzyme A (CoA), acyl CoA synthetase, oxoacyl CoA thiolase, and ubiquitin also were underexpressed in NASH. Genes that were overexpressed in NASH included complement component C3 and hepatocyte\u2013derived fibrinogen\u2013related protein, potentially contributing to impaired insulin sensitivity. In conclusion, these studies provide evidence for a transcriptional or pretranscriptional basis for impaired mitochondrial function (attenuated capacity for the dismutation of reactive oxygen species) and diminished insulin sensitivity (increased acute phase reactants) in patients with histologically progressive NASH. Further studies are required to determine the mechanism and the physiologic significance of these findings.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1053\/jhep.2003.50290","type":"journal-article","created":{"date-parts":[[2003,6,26]],"date-time":"2003-06-26T16:37:21Z","timestamp":1056645441000},"page":"244-251","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":153,"title":["Hepatic Gene Expression in Histologically Progressive Nonalcoholic 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