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Identification of novel genetic factors and genetic risk assessment models for non-viral HCC

Research Project

Project/Area Number 17K09446
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Gastroenterology
Research InstitutionHiroshima University (2018-2019)
Institute of Physical and Chemical Research (2017)

Principal Investigator

Daiki Miki  広島大学, 医系科学研究科(医), 講師 (10584592)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsSNP / 肝癌 / NASH / NAFLD / SVR / HCV / 非ウイルス性肝癌 / 肝臓学
Outline of Final Research Achievements

Recently, it was reported that a single nucleotide polymorphism (SNP) rs17047200 located within the intron of TLL1 gene was associated with development of hepatocellular carcinoma (HCC) after eradication of hepatitis C virus (HCV). As a result of our study, we observed protective tendencies of rs17047200 T allele for the risk of HCC development in SVR patients as well as chronic HCV patients and chronic HBV patients. We also observed a similar tendency for the risk of fibrosis severity in SVR patients.
The SNP in PLPNA3 is the most famous genetic factor which confers susceptibility to nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Our findings revealed that SNPs of PNPLA3 and neighbor genes were associated not only to NAFLD/NASH susceptibility, but also to HCC development with stronger effects than those for NAFLD/NASH susceptibility. In addition, a novel candidate SNP which causes T94A substitution in FABP1 might affect NASH/NAFLD-related HCC.

Academic Significance and Societal Importance of the Research Achievements

現在、肝炎ウイルス非存在下における肝癌が増加傾向であるが、そのリスク因子は十分に解明されていない。より効率的なスクリーニングを行うためにも、リスク因子のさらなる解明が急務である。遺伝的要因について解析を行った本研究の結果、これまでの報告とは異なる結果や、これまでに報告の無かった結果が得られた。これらの結果については、さらなる検証が必要ではあるものの、今後、肝発癌リスクの予測に役立つことが期待できる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (21 results)

All 2020 2019 2018 2017

All Journal Article (15 results) (of which Peer Reviewed: 15 results,  Open Access: 7 results) Presentation (6 results) (of which Int'l Joint Research: 5 results)

  • [Journal Article] Risk factors for histological progression of non-alcoholic steatohepatitis analyzed from repeated biopsy cases.2020

    • Author(s)
      Daijo K, Nakahara T, Inagaki Y, Nanba M, Nishida Y, Uchikawa S, Kodama K, Oya K, Morio K, Fujino H, Ono A, Murakami E, Yamauchi M, Kawaoka T, Miki D, Tsuge M, Hiramatsu A, Hayes CN, Imamura M, Aikata H, Ochi H, Chayama K.
    • Journal Title

      J Gastroenterol Hepatol.

      Volume: - Issue: 8 Pages: 1412-1419

    • DOI

      10.1111/jgh.14968

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparative study on the replication of HCV1b genome between wild-type and cell culture-adaptive mutant in regard to sensitivities against anti-HCV drugs.2019

    • Author(s)
      Miyayama Y, Lee H, Song H, Abe-Chayama H, Miki D, Imamura M, Chayama K, Hijikata M.
    • Journal Title

      Microbiol Immunol.

      Volume: - Issue: 4 Pages: 296-303

    • DOI

      10.1111/1348-0421.12768

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pruritus in patients with chronic liver disease and serum autotaxin levels in patients with primary biliary cholangitis.2019

    • Author(s)
      Fujino H, Tanaka M, Imamura M, Morio K, Ono A, Nakahara T, Murakami E, Kawaoka T, Takahashi S, Miki D, Tsuge M, Hiramatsu A, Aikata H, Hayes CN, Chayama K.
    • Journal Title

      BMC Gastroenterol.

      Volume: 19 Issue: 1 Pages: 169-169

    • DOI

      10.1186/s12876-019-1092-z

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ribavirin induces hepatitis C virus genome mutations in chronic hepatitis patients who failed to respond to prior daclatasvir plus asunaprevir therapy.2019

    • Author(s)
      Saito Y, Imamura M, Uchida T, Osawa M, Teraoka Y, Fujino H, Nakahara T, Ono A, Murakami E, Kawaoka T, Miki D, Tsuge M, Serikawa M, Aikata H, Abe-Chayama H, Hayes CN, Chayama K.
    • Journal Title

      J Med Virol.

      Volume: 92 Issue: 2 Pages: 210-218

    • DOI

      10.1002/jmv.25602

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Efficacy of glecaprevir and pibrentasvir treatment for genotype 1b hepatitis C virus drug resistance-associated variants in humanized mice.2019

    • Author(s)
      Osawa M, Uchida T, Imamura M, Teraoka Y, Fujino H, Nakahara T, Ono A, Murakami E, Kawaoka T, Miki D, Tsuge M, Hiramatsu A, Abe-Chayama H, Hayes CN, Makokha GN, Aikata H, Ishida Y, Tateno C, Miyayama Y, Hijikata M, Chayama K.
    • Journal Title

      J Gen Virol.

      Volume: 100 Issue: 7 Pages: 1123-1131

    • DOI

      10.1099/jgv.0.001268

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparison of intracellular responses between HBV genotype A and C infection in human hepatocyte chimeric mice2019

    • Author(s)
      Tsushima K, Tsuge M, Hiraga N, Uchida T, Murakami E, Makokha GN, Kurihara M, Nomura Motonobu, Hiyama Y, Fujino H, Ono A, Nakahara T, Yamauchi M, Abe-Chayama H, Kawaoka T, Miki D, Imamura M, Aikata H, Hayes CN, Chayama K
    • Journal Title

      Journal of Gastroenterology

      Volume: 印刷中 Issue: 7 Pages: 650-659

    • DOI

      10.1007/s00535-019-01558-w

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Real-world efficacy of glecaprevir plus pibrentasvir for chronic hepatitis C patient with previous direct-acting antiviral therapy failures.2019

    • Author(s)
      Osawa M, Imamura M, Teraoka Y, Uchida T, Morio K, Fujino H, Nakahara T, Ono A, Murakami E, Kawaoka T, Miki D, Tsuge M, Hiramatsu A, Aikata H, Hayes CN, Chayama K; Hiroshima Liver Study Group.
    • Journal Title

      J Gastroenterol.

      Volume: 54 Issue: 3 Pages: 291-296

    • DOI

      10.1007/s00535-018-1520-9

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] The impact of interferon-free direct-acting antivirals on clinical outcome after curative treatment for hepatitis C virus-associated hepatocellular carcinoma: Comparison with interferon-based therapy.2019

    • Author(s)
      Nagaoki Y, Imamura M, Nishida Y, Daijo K, Teraoka Y, Honda F, Nakamura Y, Morio K, Fujino H, Nakahara T, Kawaoka T, Tsuge M, Hiramatsu A, Kawakami Y, Miki D, Hiyama Y, Ochi H, Chayama K, Aikata H.
    • Journal Title

      J Med Virol.

      Volume: 91 Issue: 4 Pages: 650-658

    • DOI

      10.1002/jmv.25352

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Levocarnitine Use Is Associated With Improvement in Sarcopenia in Patients With Liver Cirrhosis.2019

    • Author(s)
      Hiramatsu A, Aikata H, Uchikawa S, Ohya K, Kodama K, Nishida Y, Daijo K, Osawa M, Teraoka Y, Honda F, Inagaki Y, Morio K, Morio R, Fujino H, Nakahara T, Murakami E, Yamauchi M, Kawaoka T, Miki D, Tsuge M, Imamura M, Tanaka J, Chayama K.
    • Journal Title

      Hepatol Commun.

      Volume: 22 Issue: 3 Pages: 348-355

    • DOI

      10.1002/hep4.1309

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Prevalence of NS5A resistance associated variants in NS5A inhibitor treatment failures and an effective treatment for NS5A-P32 deleted hepatitis C virus in humanized mice.2018

    • Author(s)
      Teraoka Y, Uchida T, Imamura M, Osawa M, Tsuge M, Abe-Chayama H, Hayes CN, Makokha GN, Aikata H, Miki D, Ochi H, Ishida Y, Tateno C, Chayama K; Hiroshima Liver Study Group.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 500 Issue: 2 Pages: 152-157

    • DOI

      10.1016/j.bbrc.2018.04.005

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Limitations of daclatasvir/asunaprevir plus beclabuvir treatment in cases of NS5A inhibitor treatment failure.2018

    • Author(s)
      Teraoka Y, Uchida T, Imamura M, Hiraga N, Osawa M, Kan H, Saito Y, Tsuge M, Abe-Chayama H, Hayes CN, Makokha GN, Aikata H, Miki D, Ochi H, Ishida Y, Tateno C, Chayama K.
    • Journal Title

      J Gen Virol.

      Volume: 99 Issue: 8 Pages: 1058-1065

    • DOI

      10.1099/jgv.0.001091

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Advanced liver fibrosis effects on the response to sofosbuvir-based antiviral therapies for chronic hepatitis C.2018

    • Author(s)
      Morio K, Imamura M, Kawakami Y, Nakamura Y, Hatooka M, Morio R, Fujino H, Nakahara T, Murakami E, Kawaoka T, Tsuge M, Hiramatsu A, Aikata H, Hayes CN, Miki D, Ochi H, Katamura Y, Arataki K, Moriya T, Ito H, Tsuji K, Kohno H, Waki K, Tamura T, Nakamura T, Chayama K; Hiroshima Liver Study Group.
    • Journal Title

      J Med Virol.

      Volume: 90 Issue: 12 Pages: 1834-1840

    • DOI

      10.1002/jmv.25267

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Involvement of Porphyromonas gingivalis in the progression of non-alcoholic fatty liver disease.2018

    • Author(s)
      Nakahara T, Hyogo H, Ono A, Nagaoki Y, Kawaoka T, Miki D, Tsuge M, Hiraga N, Hayes CN, Hiramatsu A, Imamura M, Kawakami Y, Aikata H, Ochi H, Abe-Chayama H, Furusho H, Shintani T, Kurihara H, Miyauchi M, Takata T, Arihiro K, Chayama K.
    • Journal Title

      J Gastroenterol.

      Volume: 53 Issue: 2 Pages: 269-280

    • DOI

      10.1007/s00535-017-1368-4

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Serum HMGB1 concentrations at 4 weeks is a useful predictor of extreme poor prognosis for advanced hepatocellular carcinoma treated with sorafenib and hepatic arterial infusion chemotherapy.2018

    • Author(s)
      Masuda K, Ono A, Aikata H, Kawaoka T, Nelson Hayes C, Teraoka Y, Daijo K, Nakamura-Inagaki Y, Morio K, Fujino H, Kan H, Uchida T, Masaki K, Kobayashi T, Nakahara T, Makokha GN, Zhang Y, Nagaoki Y, Miki D, Tsuge M, Hiramatsu A, Imamura M, Abe-Chayama H, Kawakami Y, Ochi H, Chayama K.
    • Journal Title

      J Gastroenterol.

      Volume: 53 Issue: 1 Pages: 107-118

    • DOI

      10.1007/s00535-017-1348-8

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] The risks of hepatocellular carcinoma development after HCV eradication are similar between patients treated with peg-interferon plus ribavirin and direct-acting antiviral therapy.2017

    • Author(s)
      Nagaoki Y, Imamura M, Aikata H, Daijo K, Teraoka Y, Honda F, Nakamura Y, Hatooka M, Morio R, Morio K, Kan H, Fujino H, Kobayashi T, Masaki K, Ono A, Nakahara T, Kawaoka T, Tsuge M, Hiramatsu A, Kawakami Y, Hayes CN, Miki D, Ochi H, Chayama K.
    • Journal Title

      PLoS One.

      Volume: 12 Issue: 8 Pages: e0182710-e0182710

    • DOI

      10.1371/journal.pone.0182710

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] ASSOCIATION OF FNDC5, PNPLA3 AND TM6SF2 POLYMORPHISMS WITH HEPATIC STEATOSIS IN NAFLD PATIENTS2019

    • Author(s)
      Daiki Miki, Takashi Nakahara, Eisuke Murakami, Hiromi Abe-Chayama, Hatsue Fujino, Atsushi Ono, Masami Yamauchi, Tomokazu Kawaoka, Masataka Tsuge, Akira Hiramatsu, Michio Imamura, Hiroshi Aikata, Nelson Hayes, Grace Naswa Makokha, Tatsuhiko Tsunoda, Kazuaki Chayama
    • Organizer
      The Liver Meeting 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] DIFFERENTIAL EFFECTS OF HOST GENETIC FACTORS ON HCV PERSISTENCE ACCORDING TO HCV GENOTYPES2019

    • Author(s)
      Daiki Miki, Tomokazu Kawaoka, Nelson Hayes, Hiromi Abe-Chayama, Hatsue Fujino, Grace Naswa Makokha, Atsushi Ono, Takashi Nakahara, Eisuke Murakami, Masami Yamauchi, Masataka Tsuge, Akira Hiramatsu, Michio Imamura, Hiroshi Aikata, Tatsuhiko Tsunoda, Kazuaki Chayama
    • Organizer
      The Liver Meeting 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Multiple genetic factors affecting nonalcoholic fatty liver disease and nonalcoholic steatohepatitis-related hepatocellular carcinoma in the Japanese population2019

    • Author(s)
      Daiki Miki, Yuichi Hiyama, Atsushi Ono, Masami Yamauchi, Masataka Tsuge, Hiroshi Aikata, Tatsuhiko Tsunoda, Kazuaki Chayama
    • Organizer
      11th AACR-JCA Joint Conference on Breakthroughs in Cancer Research: Biology to Precision Medicine
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 日本人における非アルコール性脂肪性肝疾患・非アルコール性脂肪肝炎関連肝細胞癌の発症に関連する宿主遺伝的要因2018

    • Author(s)
      三木大樹、柘植雅貴、山内理海、相方浩、茶山一彰
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Prevalence of NS5A Resistance Associated Variants in NS5A Inhibitor Treatment Failures and an Effective Treatment for NS5A-P32 Deleted Hepatitis C Virus in Humanized Mice2018

    • Author(s)
      Yuji Teraoka, Takuro Uchida, Michio Imamura, Mitutaka Osawa, Tomokazu Kawaoka, Masataka Tsuge, Hiromi Abe-Chayama, Nelson Hayes, Grace Naswa Makokha, Hiroshi Aikata, Daiki Miki, Hidenori Ochi, Yuji Ishida, Chise Tateno, Kazuaki Chayama
    • Organizer
      The Liver Meeting 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Association of TLL1 Polymorphism with Development of Hepatocellular Carcinoma after Hepatitis C Virus Eradication and Fibrosis Severity2018

    • Author(s)
      Daiki Miki, Tomokazu Kawaoka, Yuko Nagaoki, Nelson Hayes, Atsushi Ono, Takashi Nakahara, Eisuke Murakami, Masami Yamauchi, Masataka Tsuge, Akira Hiramatsu, Michio Imamura, Hiroshi Aikata, Hiromi Abe-Chayama, Hidenori Ochi, Tatsuhiko Tsunoda, Kazuaki Chayama
    • Organizer
      The Liver Meeting 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2021-02-19  

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