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Interactions between lipid profile and PCSK9 changes and a role of oxidatively modified LDL on DAAs treatment

Research Project

Project/Area Number 18K07907
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionShinshu University

Principal Investigator

Joshita Satoru  信州大学, 学術研究院医学系, 准教授 (90597965)

Co-Investigator(Kenkyū-buntansha) 沢村 達也  信州大学, 学術研究院医学系, 教授 (30243033)
太田 正穂  信州大学, 医学部, 特任教授 (50115333)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsC型慢性肝炎 / 直接作用型抗ウイルス剤 / プロ蛋白転換酵素サブチリシン/ケキシン9型 / 脂質の量的変動 / 脂質の質的変動 / 脂質変動 / 脂質プロファイル / ウイルス学的著効 / PCSK9 / 脂質異常症
Outline of Final Research Achievements

Direct-acting antivirals (DAAs) can achieve a high rate of a sustained virological response (SVR). This study revealed three important points as follows; 1) clinical features of normal alanine aminotransferase under DAAs treatment, 2) an SVR rate was 98% under a real-world clinical practice experience but resistance mutations should be considered for DAA selection. 3) HCV eradication by DAAs produced favorable quantitative lipid profile changes and qualitative lipid improvements along with PCSK9 recovery. Based on these above, lipids levels should therefore be monitored after successful DAAs treatment.

Academic Significance and Societal Importance of the Research Achievements

C型肝炎に対する直接作用型抗ウイルス剤(DAAs)治療のウイルス排除率は100%に近い。このDAAs治療の前後においては、脂質の量的な変動が起き、それは脂質のレギュレーターであるPCSK9の変動と関連していた。さらに、脂質の質的変動を伴うことも明らかになった。これらのことより、DAAs治療にてSVR達成例では脂質の変動に注意すべきと考えられた。また、これらの変動と心血管疾患等の二次的なアウトカムとの関連については今後の検討課題と考えられた。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (19 results)

All 2021 2020 2019 2018

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 6 results) Presentation (13 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Quantitative and qualitative lipid improvement with chronic hepatitis C virus eradication using with direct-acting antivirals2021

    • Author(s)
      Joshita S, Yamashita Y, Okamoto T, et al.
    • Journal Title

      Hepatology Research

      Volume: -

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] FAST score - a new predictive marker for HCC after SVR2020

    • Author(s)
      Joshita S and Umemura T
    • Journal Title

      Alimentary Pharmacology & Therapeutics

      Volume: 52 Pages: 1222-1223

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effectiveness of Glecaprevir/Pibrentasvir for Hepatitis C: Real-World Experience and Clinical Features of Retreatment Cases2020

    • Author(s)
      Sugiura Ayumi、Joshita Satoru、Yamashita Yuki、et al.
    • Journal Title

      Biomedicines

      Volume: 8 Issue: 4 Pages: 74-74

    • DOI

      10.3390/biomedicines8040074

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical Influence of Hepatitis C Virus Eradication by Direct-acting Antivirals on Lipid Levels and “Ningen Dock” Health Check-up Categories in Patients with Chronic Hepatitis C Virus Infection2020

    • Author(s)
      Joshita Satoru、Sugiura Ayumi、Yamazaki Tomoo、et al.
    • Journal Title

      Ningen Dock International

      Volume: 7 Pages: 19-25

    • NAID

      130007868643

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical impact of normal alanine aminotransferase on direct‐acting antiviral outcome in patients with chronic hepatitis C virus infection2019

    • Author(s)
      Joshita Satoru、Sugiura Ayumi、Umemura Takeji、Yamazaki Tomoo、Fujimori Naoyuki、Matsumoto Akihiro、Usami Yoko、Tanaka Eiji
    • Journal Title

      JGH Open

      Volume: - Issue: 4 Pages: 574-581

    • DOI

      10.1002/jgh3.12296

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Past history of hepatocellular carcinoma is an independent risk factor of treatment failure in patients with chronic hepatitis C virus infection receiving direct-acting antivirals2018

    • Author(s)
      Ayumi Sugiura, Satoru Joshita, Takeji Umemura, et al.
    • Journal Title

      Journal of Viral Hepatitis

      Volume: 25 Issue: 12 Pages: 1462-1471

    • DOI

      10.1111/jvh.12973

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] ALT正常C型慢性肝炎患者に対して全例「ウイルス排除」に向けた直接作用型抗ウイルス剤治療の臨床的意義2020

    • Author(s)
      城下智、杉浦亜弓、梅村武司
    • Organizer
      第106回日本消化器病学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] DAA治療によるHCV排除はHDL-Cの量的変動のみならず、質的な変動にも関与する2020

    • Author(s)
      城下智、杉浦亜弓、梅村武司
    • Organizer
      第56回日本肝臓学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 直接作用型抗ウイルス剤によるHCV排除が脂質代謝系および脂質プロファイルの量的変動と質的変動に与える影響2020

    • Author(s)
      城下智、山下裕騎、梅村武司
    • Organizer
      第43回日本肝臓学会東部会
    • Related Report
      2020 Annual Research Report
  • [Presentation] C型肝炎におけるPNALT症例の特徴とDAAs治療の意義2019

    • Author(s)
      城下智、杉浦亜弓、梅村武司、田中榮司
    • Organizer
      第116回日本内科学会講演会
    • Related Report
      2019 Research-status Report
  • [Presentation] 慢性肝疾患におけるATXおよびM2BPGiの非侵襲的病期診断マーカーとしての有用性とその臨床的意義2019

    • Author(s)
      城下智、梅村武司、田中榮司
    • Organizer
      第105回日本消化器病学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] Persistently Normal ALT C型慢性肝炎におけるDirect Acting Antivirals療法の臨床的特徴と実態2019

    • Author(s)
      城下智、杉浦亜弓、梅村武司
    • Organizer
      第55回日本肝臓学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] C型慢性肝炎のDAAs治療におけるLDL-Cの変化とPCSK9との関連2019

    • Author(s)
      城下智、杉浦亜弓、梅村武司
    • Organizer
      第55回日本肝癌研究会
    • Related Report
      2019 Research-status Report
  • [Presentation] 直接作用型抗ウイルス剤治療によるC型肝炎ウイルス排除が脂質変動と脂質判定区分の変化に与える影響2019

    • Author(s)
      城下智、杉浦亜弓、梅村武司
    • Organizer
      第60回日本人間ドック学会学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Lipoprotein-apolipoprotein changes in chronic hepatitis C patients treated with direct-acting antivirals2019

    • Author(s)
      Satoru Joshita、Ayumi Sugiura、Takeji Umemura
    • Organizer
      APASL STC 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] C型慢性肝炎のDAAs治療におけるLDL-Cの変化とPCSK9との関連2018

    • Author(s)
      城下智、杉浦亜弓、梅村武司、沢村達也、太田正穂、田中榮司
    • Organizer
      第115回日本内科学会講演会
    • Related Report
      2018 Research-status Report
  • [Presentation] Clinical impact of persistently normal ALT on HCC development in HCV patients with DAA treatment2018

    • Author(s)
      Satoru Joshita, Takeji Umemura, Eiji Tanaka
    • Organizer
      APASL STC 2018 on HCC in Yokohama
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Persistently Normal ALT C型慢性肝炎におけるDirect Acting Antivirals療法の臨床的特徴と実態2018

    • Author(s)
      城下智、梅村武司、田中榮司
    • Organizer
      第54回日本肝臓学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] C型肝炎の直接作用型抗ウイルス剤治療における脂質の量的変動プロファイルとアポリポ蛋白変動からみた脂質の質的変動に関する検討2018

    • Author(s)
      城下智、梅村武司、田中榮司
    • Organizer
      第42回日本肝臓学会東部会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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