Abstract：
BACKGROUND & AIMS:The mechanisms of treatment resistance to interferon (IFN) and ribavirin (Rib) combination therapy for hepatitis C virus (HCV) infection are not known. This study aims to gain insight into these mechanisms by exploring hepatic gene expression before and during treatment. METHODS:Liver biopsy was performed in 50 patients before therapy and repeated in 30 of them 1week after initiating combination therapy. The cells in liver lobules (CLL) and the cells in portal areas (CPA) were obtained from 12 patients using laser capture microdissection (LCM). RESULTS:Forty-three patients were infected with genotype 1 HCV, 20 of who were viral responders (genotype 1-Rsp) with treatment outcome of SVR or TR, while 23 were non-responders (genotype 1-nonRsp) with NR. Only seven patients were infected with genotype 2. Before treatment, the expression of IFN and Rib-stimulated genes (IRSGs), apoptosis-associated genes, and immune reaction gene pathways was greater in genotype 1-nonRsp than in Rsp. During treatment, IRSGs were induced in genotype 1-Rsp, but not in nonRsp. IRSG induction was irrelevant in genotype 2-Rsp and was mainly impaired in CLL but not in CPA. Pathway analysis revealed that many immune regulatory pathways were induced in CLL from genotype 1-Rsp, while growth factors related to angiogenesis and fibrogenesis were more induced in CPA from genotype 1-nonRsp. CONCLUSIONS:Impaired IRSGs induction in CLL reduces the sensitivity to treatment for genotype 1 HCV infection. CLL and CPA in the liver might be differentially involved in treatment resistance. These findings could be useful for the improvement of therapy for HCV infection.
journal_name
J Hepatoljournal_title
Journal of hepatologyauthors
Honda M,Nakamura M,Tateno M,Sakai A,Shimakami T,Shirasaki T,Yamashita T,Arai K,Yamashita T,Sakai Y,Kaneko Sdoi
10.1016/j.jhep.2010.04.036subject
Has Abstractpub_date
2010-11-01 00:00:00pages
817-26issue
5eissn
0168-8278issn
1600-0641pii
S0168-8278(10)00610-0journal_volume
53pub_type
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更新日期：2007-01-01 00:00:00
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更新日期：1998-04-01 00:00:00
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doi：10.1016/j.jhep.2008.07.037
更新日期：2009-02-01 00:00:00
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doi：10.1016/0168-8278(91)90036-b
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pub_type： 临床试验,杂志文章,随机对照试验
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pub_type： 杂志文章,评审
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pub_type： 杂志文章
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