利巴韦林
医学
聚乙二醇干扰素
基因表达谱
丙型肝炎病毒
肝活检
基因表达
免疫学
干扰素
基因型
基因
ISG15
病毒载量
α-干扰素
实时聚合酶链反应
病毒
内科学
活检
生物
遗传学
泛素
作者
Li Chen,Ivan Borozan,Jordan J. Feld,Jing Sun,Laura Lee Tannis,Catalina Coltescu,Jenny Heathcote,Aled M. Edwards,Ian D. McGilvray
标识
DOI:10.1053/j.gastro.2005.01.059
摘要
Pegylated interferon (IFN)-alpha plus ribavirin is the most effective treatment of chronic hepatitis C but has unpleasant side effects and high costs. A large proportion of patients do not respond to therapy for reasons that are unclear. We used gene expression profiling to investigate the molecular basis for treatment failure.Expression profiling was performed on percutaneous needle liver biopsy specimens taken before therapy. Gene expression levels were compared among 15 nonresponder, 16 responder, and 20 normal liver biopsy specimens. Differential gene expression was confirmed using real-time polymerase chain reaction.We identified 18 genes whose expression differed significantly between all responders and all nonresponders (P < .005). Many of these 18 genes are IFN sensitive and 2 (ISG15/USP18) are linked in a novel IFN-regulatory pathway, suggesting a possible rationale for treatment resistance. Using a number of independent classifier analyses, an 8-gene subset accurately predicted treatment response for 30 of 31 patients. The classifier analyses were applicable to patients with genotype 1 infection and were not correlated with viral load, disease activity, or fibrosis.Hepatic gene expression profiling identified consistent differences in patients who subsequently fail treatment with pegylated IFN-alpha plus ribavirin: up-regulation of a specific set of IFN-responsive genes predicts nonresponse to exogenous therapy. These data may be of use in predicting clinical responses to treatment.
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