New clinical classification and the criteria for predicting long-term outcome in primary biliary cirrhosis
Project/Area Number |
20590800
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Gastroenterology
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Research Institution | Department of Clinical Research, National Hospital Organization Nagasaki Medical Center |
Principal Investigator |
NAKAMURA Minoru Department of Clinical Research, National Hospital Organization Nagasaki Medical Center, 臨床研究センター, 客員研究員 (40217906)
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Co-Investigator(Kenkyū-buntansha) |
KOMORI Atumasa 独立行政法人国立病院機構長崎医療センター, 臨床研究センター, 室長 (50234901)
ISHIBASHI Hiromi 独立行政法人国立病院機構長崎医療センター, 臨床研究センター, センター長 (80127969)
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Project Period (FY) |
2008 – 2010
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Project Status |
Completed (Fiscal Year 2010)
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Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2010: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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Keywords | 原発性胆汁性肝硬変 / 予後予測 / SNPs / 遺伝子多型 / HLA / 病型分類 / 抗gp210抗体 / 抗セントロメア抗体 / 一塩基多型(SNP) / HLA-DRB1 / 予後 / バイオマーカー / 黄疸型進行 / 非黄疸型進行 / 長期予後診断 |
Research Abstract |
In order to establish a clinical classification and a criteria for predicting long-term outcome in primary biliary cirrhosis (PBC), we studied the autoantibodies (anti-gp210, anti-centromere), HLA-DRB1 and SNPs of various molecules concerning immune-regulation and bile acid metabolism. HLA-DRB1*0803 and CTLA4 SNPs confer susceptibility to PBC development. Positive anti-gp210 and anti-centromere antibodies as well as HLA-DRB1*1502 and *0901 are risk factors for the progression to liver cirrhosis or portal hypertension, while positive anti-gp210 antibodies as well as SNPs of MDR3 and integrin ・V are associated with progression to hepatic failure. Since positive anti-gp210 antibodies is a strong risk factor for jaundice-type progression (OR>30), the treatment for PBC became possible with monitoring anti-gp210 antibodies as a serological biomarker. Furthermore, our proposal of PBC progression, anti-gp210 type progression and anti-centromere type progression, was supported by the level of genetic polymorphisms.
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Report
(4 results)
Research Products
(59 results)
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[Journal Article] The genetic polymorphisms of CTLA4 and SLC4A2 are differentially associated with the pathogenesis of primary biliarycirrhosis in Japanese patients.2011
Author(s)
Aiba Y, Nakamura M, Joshita S, Inamime T, Komori A, Yoshizawa K, Umemura T, Migita K, Yatsuhashi H, Nakamuta M, Fukushima N, Saito A, Kouno H, Ota H, Muro T, Hayashi S, Watanabe Y, Nakamura Y, Komeda T, Shimada M, Tsukamoto K, Tanaka E, Ishibashi H, the PBC Study Group in NHOSLJ.
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Journal Title
J Gastroenterol Epub ahead of print
Related Report
Peer Reviewed
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[Journal Article] Evaluation of risk factors for the development of cirrhosis in autoimmune hepatitis : Japanese NHO-AIH prospective study.2011
Author(s)
Migita K, Watanabe Y, Jiuchi Y, Nakamura Y, Saito A, Yagura M, Morimoto H, Shimada M, Mita E, Hijioka T, Yamashita H, Takezaki E, Muro T, Sakai H, Nakamuta M, Abiru S, Yano K, Komori A, Yatsuhashi H, Nakamura M, Ishibashi H
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Journal Title
J Gastroenterol 46 Suppl 1
Pages: 56-62
NAID
Related Report
Peer Reviewed
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[Journal Article] A polymorphism in the integrin・V subunit gene affects the progression of primary biliary cirrhosis in Japanese patients.2011
Author(s)
Inamine T, Nakamura M, Kawauchi A, Shirakawa Y, Hashiguchi H, Aiba Y, Taketomi A, Shirabe K, Nakamuta M, Hayashi S, Saoshiro T, Komori A, Yatsuhashi H, Kondo S, Omagari K, Maehara Y, Ishibashi H, Tsukamoto K, the PBC Study Group in NHOSLJ.
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Journal Title
J Gastroenterol 46
Pages: 676-686
Related Report
Peer Reviewed
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[Journal Article] Serum Baff and APRIL levels in patients with PBC.2011
Author(s)
Migita K, Ilyassova B, Kovzel EF, Nersesov A, Maeda Y, Komori A, Ito M, Yano K, Yatsuhashi H, Ishibashi H, Nakamura M
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Journal Title
Clin Immunol 134
Pages: 217-225
Related Report
Peer Reviewed
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[Journal Article] Analysis of HLA-DRB1 polymorphisms in Japanese patients with primary biliary cirrhosis (PBC) : the HLA-DRB1 polymorphism determines the relative risk of antinuclear antibodies for disease progression in PBC.2011
Author(s)
Nakamura M, Yasunami M, Kondo H, Horie H, Aiba Y, Komori A, Migita K, Yatsuhashi H, Ito M, Shimoda S, Ishbiashi H, PBC Study Group in NHOSLJ.
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Journal Title
Hepatol Res 40
Pages: 494-504
NAID
Related Report
Peer Reviewed
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[Journal Article] Increased expression of toll-like- receptor 3 in intrahepatic biliary epithelial cells at sites of ductular reaction in diseased livers.2008
Author(s)
Nakamura M, Funami K, Komori A, Yokoyama T, Aiba Y, Araki A, Takii Y, Ito M, Matsuyama M, Koyabu M, Migita K, Taniguchi K, Fujioka H, Yatsuhashi H, Matsumoto M, Ishibashi H, Seya T
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Journal Title
Hepatol Int 2
Pages: 222-230
Related Report
Peer Reviewed
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[Journal Article] CD4 T-cell autoreactivity to the mitochondrial autoantigen PDC-E2 in AMA-negative primary biliary cirrhosis.2008
Author(s)
Shimoda S, Miyakawa H, Nakamura M, Ishibashi H, Kikuchi K, Kita H, Niiro H, Arinobu Y, Ono N, MacKay IR, Gershwin ME, Akashi K.
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Journal Title
J Autoimmun 31
Pages: 110-115
Related Report
Peer Reviewed
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[Journal Article]2008
Author(s)
中村稔, 下田愼治, 小森敦正, 石橋大海
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Journal Title
BIO Clinica(原発性胆汁性肝硬変における抗gp210抗体の臨床的意義)
Pages: 1136-1143
Related Report
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[Journal Article] Biliary epithelial cells and primary biliary cirrhosis : the role of liver- infiltrating mononuclear cells.
Author(s)
Shimoda S, Harada K, Niiro H, Yoshizumi T, Soejima Y, Taketomi A, Maehara Y, Tsuneyama K, Nakamura M, Komori A, Migita K, Nakanuma Y, Ishibashi H, Selmi C, Gershwin ME.
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Journal Title
Hepatology 2008 47
Pages: 958-65
Related Report
Peer Reviewed
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[Presentation] Positive anti-gp210 antibodies is a strong risk factor for bile duct loss and hepatitis which induce jaundice-type progression of primary biliaruy cirrhosis in Japanese patients.2010
Author(s)
Nakamura M, Ito M, Zeniya M, Ohira H, Hashimoto E, Kaneko S, Ueno Y, Kikuchi K, Onji M,Shimoda S, Komori A, Takikawa H, Onishi S, Tsubouchi H, Ishibashi H, Nakanuma Y
Organizer
EASL The International Liver Congress 2010 (A1109)
Place of Presentation
Vienna
Related Report
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[Presentation] Analysis of HLA-DRB1 polymorphism in Japanese patients with primary biliary cirrhosis (PBC) - HLA-DRB1 polymorphism determines the relative risk of anti-nuclear antibodies for the disease-progression in PBC.2009
Author(s)
Nakamura M, Yasunami M, Kondo H, Aiba Y, Komori A, Migita K, Yatsuhashi H, Nakamuta M, Hayashi S, Saito A, Honda K, Shimada M, Watanabe Y, Yagura M, Kohno H, Sugi K, Ota H, Komatsu T, Mannami T, Koga M, Satoh T, Takesaki E, Yamamoto T, Oohara Y, Masaki N, Ishibasi H
Organizer
Hepatology(Volume 50, Number 4 (Suppl), October 2009, 1004A, 1521.)
Place of Presentation
Boston
Year and Date
2009-11-03
Related Report
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[Presentation] 原発性胆汁性肝硬変の予後診断法の確立のための遺伝子解析2009
Author(s)
中村稔、塚元和弘、安波道郎、近藤久義、相葉佳洋, 小森敦正、右田清志、八橋弘、竿代丈夫、林茂樹、中牟田誠、本田浩一、杉和洋、島田昌明、小林正和、渡部幸夫、森本日出雄、矢倉道泰、正木尚彦、高野弘嗣、竹崎英一、小松達司、山下晴弘、加藤道夫、古賀満明、長岡進矢、矢野公士、阿比留正剛、石橋大海
Organizer
第45回日本肝臓学会総会(肝臓 50巻 2009, suppl.(1), A162, 0-78.)
Place of Presentation
神戸
Related Report
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[Presentation] 原発性胆汁性肝硬変の予後予測診断法の確立2008
Author(s)
中村稔, 大石裕樹, 相葉佳洋, 小森敦正, 右田清志, 八橋弘, 竿代丈夫, 中牟田誠, 本田浩一, 島田昌明, 小林正和, 渡部幸夫, 林茂樹, 古賀満明, 森本日出雄, 正木尚彦, 近藤久義, 大曲勝久, 安波道郎, 塚元和弘, 石橋大海
Organizer
第44回日本肝臓学会総会(肝臓 49巻 2008, suppl.(1), A184, 0-115.)
Place of Presentation
松山
Related Report
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[Presentation] 培養ヒト肝内胆管上皮細胞の急性相反応からみた遺伝子発現の可能性2008
Author(s)
小森敦正, 植村隆, 藤原紳祐, 相葉佳洋, 中村稔, 矢野公士, 藤岡ひかる, 右田清志, 八橋弘, 石橋大海
Organizer
第44回日本肝臓学会総会(一般演題,セッション60:胆管・胆汁うっ滞2)(肝臓 49 Suppl.(1):A235,2008.04.30)
Place of Presentation
愛媛
Related Report
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