Differential interferon signaling in cells in liver lobules and portal areas under treatment for chronic hepatitis C

フォーマット:

論文

責任表示:

Honda, Masao ; Nakamura, Mikiko ; Tateno, Makoto ; Sakai, Akito ; Shimakami, Tetsuro ; Shirasaki, Takayoshi ; Yamashita, Tatsuya ; Arai, Kuniaki ; Yamashita, Taro ; Sakai, Yoshio ; Kaneko, Shuichi

言語:

英語

出版情報:

European Association for the Study of the Liver / Elsevier, 2010-01-01

著者名:

Honda, Masao

Nakamura, Mikiko

Tateno, Makoto

Sakai, Akito

Shimakami, Tetsuro

Shirasaki, Takayoshi

Yamashita, Tatsuya

Arai, Kuniaki

Yamashita, Taro

Sakai, Yoshio

Kaneko, Shuichi

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掲載情報:

Journal of Hepatology

ISSN:

0168-8278      

巻:

53

通号:

5

開始ページ:

817

終了ページ:

826

バージョン:

author

概要:

金沢大学医薬保健研究域医学系<br />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 th … ese 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 1 week 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. © 2010 European Association for the Study of the Liver. 続きを見る

URL:

http://hdl.handle.net/2297/25263