Identification of a specific gene expression pattern associated with HCV-induced pathogenesis in HCV- and HCV/HIV-infected individuals

摘要

Gene expression profiling was performed on liver biopsies from 28 patients (12 HCV and 16 HCV/HlV infected) in an attempt to understand the mechanisms of HCV liver disease in the presence and absence of HIV cointection. The data were compared with clinical observations and a gene expression database obtained for transplant HCV-infected samples. This is the first report of functional genomics being used to compare intrahepatic gene expression profiles of HCV- and HCWHIV-infected individuals. Significantly, the intrahepatic global gene expression profiles do not differ between HCV- and HCWHIV-infected individuals. However, a Subset of patients was identified who share a specific pattern of gene expression, termed the enhanced gene expression (EGE) pattern. Specifically, the EGE (+) patients show a dramatic decreased expression of multiple genes associated with the FAS-apoptosis pathway and increased expression of lymphocyte adhesion molecules and lyrnphocyte-specific genes. The EGE (+) patients also have partially impaired Type I and II IFN-mediated antiviral responses, including a lack of induction of the anti-fibrogenic cytokine IFN-gamma. Importantly, the pattern of gene expression observed in EGE (+) patients has similarities to patients who developed fibrosis within I year of receiving a liver transplant. (c) 2006 Elsevier Inc. All rights reserved.