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dc.contributor.authord'Avigdor, William Mark Henry
dc.date.accessioned2015-10-14
dc.date.available2015-10-14
dc.date.issued2015-01-06
dc.identifier.urihttp://hdl.handle.net/2123/13896
dc.description.abstractChronic hepatitis C virus (HCV) infection causes liver disease that can lead to cirrhosis and hepatocellular carcinoma (HCC). The predominant HCV genotypes in Australia (G1 and G3) differ in the pathogenesis of liver injury and treatment response, but the molecular mechanisms are not well defined. The aim of this research is to determine specific HCV genotype differences in the global mRNA and miRNA expression associated with HCV induced liver injury. The mRNA transcriptome and miRNA expression of HCV induced liver injury (G1 or G3) was characterised in progressive liver injury, advanced cirrhosis from individuals with and without HCC compared with non diseased liver using Illumina Whole genome BeadChip Arrays and Taqman Low Density Arrays. Further, the mRNA expression of HCV genotype-specific core chimeric JFH1 infected Huh 7 cells following lipid loading was similarly characterised. In progressive liver injury, HCV genotype is associated with the greatest variation in gene expression between individuals. There is increased expression of interferon stimulated genes, inflammation and fibrosis genes in G3, and increased expression of fatty acid degradation and cholesterol transport associated genes in G1. In advanced cirrhosis, the cirrhotic gene signature masks the genotype specific gene expression patterns. No gene signature distinguishes cirrhotic liver injury from individuals with and without HCC. The miRNA expression is associated with the severity of disease with no HCV genotype specific differences identified. The mRNA transcriptome of a hepatic cell line infected with chimeric HCV specific for the HCV core protein is consistent with the in vivo analysis with increased expression of genes associated with fibrosis and proliferation in G3, but no differences were observed in fatty acid metabolism. In conclusion, the HCV genotype specific differences in gene expression are more defined in progressive liver injury compared with changes seen in advanced cirrhosis.en_AU
dc.rightsThe author retains copyright of this thesis. It may only be used for the purposes of research and study. It must not be used for any other purposes and may not be transmitted or shared with others without prior permission.en_AU
dc.subjectHCVen_AU
dc.subjectgenotypeen_AU
dc.subjectsteatosisen_AU
dc.subjectHCCen_AU
dc.subjectgene expressionen_AU
dc.subjectmiRNAen_AU
dc.titleDifferential gene expression in HCV liver injuryen_AU
dc.typeThesisen_AU
dc.date.valid2015-01-01en_AU
dc.type.thesisDoctor of Philosophyen_AU
usyd.facultySydney Medical Schoolen_AU
usyd.degreeDoctor of Philosophy Ph.D.en_AU
usyd.awardinginstThe University of Sydneyen_AU


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