Comprehensive analysis of hepatocarcinogenesis risk after antiviral therapy using next-generation sequencing technology
| Project/Area Number |
16K09349
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | University of Yamanashi |
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Principal Investigator |
Maekawa Shinya 山梨大学, 大学院総合研究部, 講師 (70397298)
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| Research Collaborator |
Enomoto Nobuyuki
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 抗ウイルス治療後肝癌 / 次世代シークエンス / HBV / HCV / ウイルスゲノム解析 / 癌関連遺伝子解析 / リキッドバイオプシー / Ｂ型肝炎ウイルス(HBV) / Ｃ型肝炎ウイルス(HCV) / 抗ウイルス治療 / 肝発癌 / 宿主癌関連遺伝子解析 / HCC / ＨＣＶ / ＨＢＶ / 癌関連遺伝子変異 / 次世代シークエンサー / C型肝炎ウイルス / B型肝炎ウイルス / 包括的解析 |
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| Outline of Final Research Achievements |
● The major issue in the era of advanced antiviral therapy is hepatocellular carcinoma (HCC) developing after antiviral therapy. In this study, we aimed to clarify HCC risk by analysis of viral genome and host gene using next-generation sequencing technology.
● In hepatitis C, we found that viral factors (HCV core and NS5A mutation) and host factor (IL28B SNP) significantly changed the incidence of HCC after treatment. In hepatitis B, we identified the preS region 132-141 amino acid region involved in the development of liver disease advancement. In addition, we clarified the importance of hTERT promoter mutation in HCCs occurring after antiviral treatment, and constructed a hTERT promoter mutation detection system by liquid biopsy.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究によって、抗ウイルス治療後肝発癌・病態進展リスクとしてのウイルスゲノム領域あるいは宿主領域がC型肝炎・B型肝炎において明らかになり、また肝癌診断・治療モニターとしてのリキッドバイプシーシステムの構築が可能であった。これらは肝癌実臨床における有用なバイオマーカーとなり、これらを用いることでHCC発見のための効率よいサーベイランスの実施、あるいは発癌症例に対する適切な治療法選択が可能となることが考えられた。一方、これらの多くは宿主の免疫状態と関連する因子であり、免疫制御が肝癌制御のキーとなることが示され、学術的にも重要な意義が得られた。
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Report
(4 results)
Research Products
(23 results)
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[Journal Article] HBV patients with low HBsAg and high HBcrAg titers have a high risk of HBV-related HCC.2019
Author(s)
Suzuki Y, Maekawa S, Komatsu N, Sato N, Tatsumi A, Miura M, Muraoka M, Nakakuki N, Shindo H, Amemiya F, Takano S, Nakayama Y, Fukasawa M, Yamaguchi T, Inoue T, Sato T, Sakamoto M, Yamashita A, Moriishi K, Enomoto N
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Journal Title
Hepatol Res
Volume: 49
Pages: 51-63
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] HBV preS deletion mapping using deep sequencing demonstrates a unique association with viral markers.2019
Author(s)
Suzuki Y, Maekawa S, Komatsu N, Sato M, Tatsumi A, Miura M, Matsuda S, Muraoka M, Nakakuki N, Amemiya F, Takano S, Fukasawa M, Nakayama Y, Yamaguchi T, Inoue T, Sato T, Sakamoto M, Yamashita A, Moriishi K, Enomoto N
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Journal Title
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Association Between Alanine Aminotransferase Elevation And UGT1A1*6 Polymorphisms In Daclatasvir And Asunaprevir Combination Therapy For Chronic Hepatitis C.2018
Author(s)
Maekawa S, Sato M, Kuratomi N, Inoue T, Suzuki Y, Tatsumi A, Miura M, Matsuda S, Muraoka M, Nakakuki N, Amemiya F, Takano S, Fukasawa M, Nakayama Y, Yamaguchi T, Sato T, Sakamoto M, Murakawa M, Nakagawa M, Asahina Y, Enomoto N.
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Journal Title
J Gastroenterol
Volume: 印刷中
Pages: 780-786
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Inhibitory effects of metachromin A on hepatitis B virus production via impairment of the viral promoter activity.2017
Author(s)
Yamashita A, Tamaki M, Kasai H, Tanaka T, Otoguro T, Ryo A, Maekawa S, Enomoto N, de Voogd NJ, Tanaka J, Moriishi K.
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Journal Title
Antiviral Res.
Volume: 145
Pages: 136-145
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Cinnamic acid derivatives inhibit hepatitis C virus replication via the induction of oxidative stress.2017
Author(s)
Amano R, Yamashita A, Kasai H, Hori T, Miyasato S, Saito S, Yokoe H, Takahashi K, Tanaka T, Otoguro T, Maekawa S, Enomoto N, Tsubuki M, Moriishi K.
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Journal Title
Antiviral Res.
Volume: 145
Pages: 123-130
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Hepatic Amyloidosis with an Extremely High Stiffness Value on Magnetic Resonance Elastography2016
Author(s)
Matsuda S, Motosugi U, Kato R, Muraoka M, Suzuki Y, Sato M, Shindo K, Nakayama Y, Inoue T, Maekawa S, Sakamoto M, Enomoto N.
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Journal Title
MRMS
Volume: 15
Issue: 3
Pages: 251-2
DOI
NAID
ISSN
1347-3182, 1880-2206
Related Report
Peer Reviewed
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