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However, the effect of embolization\u2010induced hypoxia on liver cirrhosis has rarely been concerned.<\/jats:p><\/jats:sec>Methods<\/jats:title>Serum levels of alanine aminotransferase, aspartate aminotransferase, and albumin were used to detect liver injury. Hepatic artery ligation was performed in carbon tetrachloride\u2010induced rat hepatic fibrosis model to mimic the effect of hepatic hypoxia on liver fibrosis after TACE<\/jats:styled-content>. S<\/jats:styled-content>irius R<\/jats:styled-content>ed staining and immunohistochemical analysis of alpha\u2010smooth muscle actin (\u03b1\u2010SMA<\/jats:styled-content>) were used to detect the activation of hepatic stellate cells. Moreover, the expression of hypoxia and fibrosis\u2010related molecules were analyzed at protein and\/or mRNA<\/jats:styled-content> level.<\/jats:p><\/jats:sec>Results<\/jats:title>Patients showed a significant increase in alanine aminotransferase and aspartate aminotransferase (P<\/jats:italic>\u2009=\u20090.006), accompanied by a decrease in albumin (P<\/jats:italic>\u2009=\u20090.005) after repeated TACE<\/jats:styled-content>. Hepatic artery ligation significantly promoted carbon tetrachloride\u2010induced rat liver fibrosis progression as indicated by S<\/jats:styled-content>irius R<\/jats:styled-content>ed and \u03b1\u2010SMA<\/jats:styled-content> staining, as well as increased expression of hypoxia\u2010inducible factor (HIF<\/jats:styled-content>)\u20101\u03b1, transforming growth factor (TGF)\u2010\u03b21, and vascular endothelial growth factor (VEGF). Conditioned media of hypoxia\u2010treated L<\/jats:styled-content>02 cells induced the expression of C<\/jats:styled-content>ollagen I<\/jats:styled-content><\/jats:italic> and \u03b1\u2010SMA<\/jats:styled-content><\/jats:italic> in LX<\/jats:styled-content>\u20102 cells, which was inhibited by HIF<\/jats:styled-content>\u20101\u03b1 small interfering RNA<\/jats:styled-content>. Finally, HIF<\/jats:styled-content>\u20101\u03b1 inhibitor LW<\/jats:styled-content>6 attenuated the hypoxia\u2010induced fibrosis progression in vivo<\/jats:italic>.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Our data demonstrate that TACE<\/jats:styled-content>\u2010induced hepatic hypoxia aggravates the fibrosis progression in peritumoral liver tissue, thus leads to the deterioration of liver function. Intervention of HIF<\/jats:styled-content>\u20101\u03b1 might be a valuable strategy to optimize the efficacy and reduce the complication of TACE<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jgh.12873","type":"journal-article","created":{"date-parts":[[2014,12,30]],"date-time":"2014-12-30T10:25:15Z","timestamp":1419935115000},"page":"925-932","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Transarterial chemoembolization aggravated peritumoral fibrosis via hypoxia\u2010inducible factor\u20101\u03b1 dependent pathway in hepatocellular carcinoma"],"prefix":"10.1111","volume":"30","author":[{"given":"Kai","family":"Qu","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary Surgery First Affiliated Hospital of Medical College Xi'an Jiaotong University Xi'an 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