Establishment of the education system to the early diagnosis of the chronic liver disease in Indonesia

• Project/Area Number: 16H05826
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 海外学術
• Research Field: Epidemiology and preventive medicine
• Research Institution: Kobe University
• Principal Investigator: Hayashi Yoshitake 神戸大学, 保健学研究科, 教授 (50189669)
• Co-Investigator(Kenkyū-buntansha): 靭 千恵 神戸大学, 保健学研究科, 特命助教 (50570834) ; 亀岡 正典 神戸大学, 保健学研究科, 教授 (60281838) ; 矢野 嘉彦 神戸大学, 医学研究科, 講師 (60419489)
• Research Collaborator: LUSIDA Maria Inge ; RATNASARI Neneng ; MUHAMMAD Hanafi
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000); Fiscal Year 2018: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2017: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2016: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
• Keywords: インドネシア / 肝炎ウイルス / 肝がん / 早期診断 / 肝細胞癌 / 薬剤耐性 / 医学 / インドネシア国 / 肝疾患 / 教育 / B型肝炎ウイルス / 画像診断 / 疫学調査 / 教育活動 / 疫学 / 予防医学

Outline of Final Research Achievements

The epidemiology of chronic liver diseases and liver cancer in Indonesia was examined with collaborators in Gadja Mada University and Airlangga University. Hepatitis B virus was involved in more than half of liver cancer, and the prevention of spread of hepatitis B was regarded as urgent issues. However, the positive prevalence of HBs antigen was still 2 to 4% among schoolchildren, and was suggested that there are remaining problems of vaccine program. In this study, the viral dynamics of quasispecies in relation to disease progression or antiviral therapy was examined and clarified.
In addition, the antiviral activities of the natural resources peculiar to Indonesia were examined in vitro, and proved the efficacy from several ingredients. This result will give a scientific evidence for traditional medicine and support a development of novel antiviral drugs.

Academic Significance and Societal Importance of the Research Achievements

本研究を通じてインドネシア国の臨床医および基礎研究医とともに学術研究を行うネットワークを構築した。学術的には、同国の肝炎ウイルスの持続感染や病態に関わる宿主遺伝子およびウイルス遺伝子変異についての一端を解明した。また同国の天然資源において抗ウイルス効果を検証し、伝統的治療の科学的立証につながる研究をおこなった。
社会的意義としては、同国の肝臓がんの現状と問題点の抽出を行うことができ、医療水準の向上や早期診断治療にむけた患者への啓蒙活動を行う上での基盤が形成された。

Research Products

• [Int'l Joint Research] ガジャマダ大学/アイルランガ大学(インドネシア)
• [Journal Article] Association between quasispecies variants of hepatitis B virus, as detected by high throughput sequencing, and progression of advanced liver disease in Indonesian patients (2019)
  • Author(s): Putri WA, Yano Y, Yamani LN, Liang Y, Mardian Y, Utsumi T, Soetjipto, Lusida MI, Hayashi Y.
  • Journal Title: Molecular Medicine Reports Volume: 印刷中
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Analysis of hepatitis B virus genotype and gene mutation in patients with advanced liver disease in East Kalimantan, Indonesia (2019)
  • Author(s): Wahyuni RM, Utsumi T, Juniastuti, Yano Y, Murti IS, Amin M, Yamani LN, Istimagfiroh A, Purwono PB, Soetjipto, Lusida MI, Hayashi Y
  • Journal Title: Biomedical Reports Volume: 10 Pages: 303-310
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Association Between HBx Variations and Development of Severe Liver Disease Among Indonesian Patients (2019)
  • Author(s): Putri WA, Yano Y, Yamani LN, Lusida MI, Soetjipto, Liang Y, Mardian Y, Wasityastuti W, Hayashi Y
  • Journal Title: Kobe J Med Sci Volume: 65
  • NAID: 120006645703
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Quasispecies variant of pre-S/S gene in HBV-related hepatocellular carcinoma with HBs antigen positive and occult infection (2018)
  • Author(s): Hatazawa Yuri、Yano Yoshihiko、Okada Rina、Tanahashi Toshihito、Hayashi Hiroki、Hirano Hirotaka、Minami Akihiro、Kawano Yuki、Tanaka Motofumi、Fukumoto Takumi、Murakami Yoshiki、Yoshida Masaru、Hayashi Yoshitake
  • Journal Title: Infectious Agents and Cancer Volume: 13 Issue: 1 Pages: 1-8
  • DOI: 10.1186/s13027-018-0179-4
  • NAID: 120006398795
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Early changes in quasispecies variant after antiviral therapy for chronic hepatitis B. (2018)
  • Author(s): Liang Y, Yano Y, Putri WA, Mardian Y, Okada R, Tanahashi T, Murakami Y, Hayashi Y.
  • Journal Title: Mol Med Rep. Volume: 17 Pages: 5528-5537
  • DOI: 10.3892/mmr.2018.8551
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Genetic polymorphisms of HLA-DP and isolated anti-HBc are important subsets of occult hepatitis B infection in Indonesian blood donors: a case-control study. (2017)
  • Author(s): Mardian Y, Yano Y, Wasityastuti W, Ratnasari N, Liang Y, Putri WA, Triyono T, Hayashi Y.
  • Journal Title: Virol J. Volume: 14 Issue: 1 Pages: 1-11
  • DOI: 10.1186/s12985-017-0865-7
  • NAID: 120006373794
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Difference of polymorphism VEGF-gene rs699947 in Indonesian chronic liver disease population. (2017)
  • Author(s): Ratnasari N, Nurdjanah S, Sadewa AH, Hakimi M, Yano Y.
  • Journal Title: PLoS One. Volume: 12 Issue: 8 Pages: 1-12
  • DOI: 10.1371/journal.pone.0183503
  • NAID: 120006373793
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Profile of Mutations in the Reverse Transcriptase and Overlapping Surface Genes of Hepatitis B Virus (HBV) in Treatment-Naïve Indonesian HBV Carriers (2017)
  • Author(s): 4.Yamani LN, Yano Y, Utsumi T, Wasityastuti W, Rinonce HT, Widasari DI, Juniastuti, Lusida MI, Soetjipto, Hayashi Y.
  • Journal Title: Japanese Journal of Infectious Diseases Volume: 70 Issue: 6 Pages: 647-655
  • DOI: 10.7883/yoken.JJID.2017.078
  • NAID: 130006210251
  • ISSN: 1344-6304, 1884-2836
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Broad-spectrum antiviral agents: secreted phospholipase A2 targets viral envelope lipid bilayers derived from the endoplasmic reticulum membrane (2017)
  • Author(s): Ming Chen, Chie Aoki-Utsubo, Masanori Kameoka, Lin Deng, Yutaka Terada, Wataru Kamitani, Kei Sato, Yoshio Koyanagi, Makoto Hijikata, Keiko Shindo, Takeshi Noda, Michinori Kohara & Hak Hotta.
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 15931-15931
  • DOI: 10.1038/s41598-017-16130-w
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Hepatitis B Virus Infection in Indonesia 15 Years after Adoption of a Universal Infant Vaccination Program: Possible Impacts of Low Birth Dose Coverage and a Vaccine-Escape Mutant. (2016)
  • Author(s): 2.Purwono PB, Juniastuti, Amin M, Bramanthi R, Nursidah, Resi EM, Wahyuni RM, Yano Y, Soetjipto, Hotta H, Hayashi Y, Utsumi T, Lusida MI.
  • Journal Title: Am J Trop Med Hyg. Volume: 95 Issue: 3 Pages: 674-679
  • DOI: 10.4269/ajtmh.15-0121
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Protective effects of HLA-DPA1/DPB1 variants against Hepatitis B virus infection in an Indonesian population. (2016)
  • Author(s): 3.Wasityastuti W, Yano Y, Ratnasari N, Triyono T, Triwikatmani C, Indrarti F, Heriyanto DS, Yamani LN, Liang Y, Utsumi T, Hayashi Y.
  • Journal Title: Infect Genet Evol. Volume: 41 Pages: 177-184
  • DOI: 10.1016/j.meegid.2016.03.034
  • Peer Reviewed / Int'l Joint Research
• [Presentation] A crude extract from Cananga odorata exhibits antiviral activity against hepatitis B virus (2019)
  • Author(s): Indrasetiawan Puguh, 靭千恵, Muhammad Hanafi, Sri Hartata, 亀岡正典, 堀田博, 林祥剛
  • Organizer: 日本薬学会第139年会
• [Presentation] Methyl-pheohorbide AによるC型肝炎ウイルス感染性粒子形成阻害機構の解析 (2019)
  • Author(s): 靱千恵、堀田博
  • Organizer: 日本薬学会第139年会
• [Presentation] Profile of HBx variation in relation to HCC development among Indonesian patients (2018)
  • Author(s): Putri W Aristyaning, 矢野嘉彦, Yamani N Laura, Maria I Lusida, Soetjipto, Yujiao Liang, Yan Mardian, 林祥剛
  • Organizer: The 25th APASL Single Topic Conference on HCC Yokohama
  • Int'l Joint Research
• [Presentation] A Comparison of Quasispecies Variant of Pre-S/S Gene in HBV-related HCC with HBs Antigen Positive and Occult Infection (2018)
  • Author(s): 畑澤友里、岡田理奈、棚橋俊仁、林宏樹、平野仁崇、南晶洋、川野佑輝、田中基文、福本巧、村上善基、吉田優、林祥剛
  • Organizer: The 25th APASL Single Topic Conference on HCC Yokohama
  • Int'l Joint Research
• [Presentation] Reduced muscle (radio) density and Barcelona Clinic Liver Cancer (BCLC) staging are independently survival prognostic of Indonesia hepatocellular carcinoma (HCC) patients (2018)
  • Author(s): Mardian Yan, Yoshihiko Yano, Neneng Ratnasari, Lina Choridah, Fahmi Indrati, Putut Bayupurnama, Catharina Triwikatwani, Nurhuda H Setiawan, Yoshitake Hayashi
  • Organizer: Internatinal Digestive Disease Forum (IDDF) 2018
  • Int'l Joint Research
• [Presentation] 進行肝疾患おけるHBVウイルス多様性の変化－インドネシア人の次世代シークエンサーを用いた解析から (2018)
  • Author(s): 矢野嘉彦、林宏樹、安冨栄一郎、畑澤友里、平野仁崇、南晶洋、川野佑輝、林祥剛
  • Organizer: 第54回日本肝臓学会総会
• [Presentation] B型慢性肝炎におけるX領域の多様性が病態の進行に関与する-インドネシア国における解析から- (2017)
  • Author(s): 矢野 嘉彦
  • Organizer: 第53回日本肝臓学会総会
• [Presentation] Single-Nucleotide Polymorphism in HLA DPA1 Gene Associates with Occult Hepatitis B Infection (OBI) in Indonesian Blood Donors (2017)
  • Author(s): Yan Mardian
  • Organizer: アジア太平洋肝臓学会（APASL）
  • Place of Presentation: 上海
  • Int'l Joint Research
• [Presentation] Quasispecies variant of HBV X region detected by Next Generation Sequencing related to progression Advanced Liver Disease among Indonesian Patients (2017)
  • Author(s): Wahyu Aristyaning Putri
  • Organizer: アジア太平洋肝臓学会（APASL）
  • Place of Presentation: 上海
  • Int'l Joint Research
• [Presentation] Single-Nucleotide Polymorphism in HLA DPA1 Gene Associates with Occult Hepatitis B Infection (OBI) in Indonesian Blood Donors (2016)
  • Author(s): Yan Mardian
  • Organizer: APASL STC 2016
  • Place of Presentation: 北京
  • Int'l Joint Research
• [Presentation] Quasispecies variant of HBV X region detected by Deep Sequencing related to progression Advanced Liver Disease in Indonesian Patients (2016)
  • Author(s): Wahyu Aristyaning Putri
  • Organizer: APASL STC 2016
  • Place of Presentation: 北京
  • Int'l Joint Research
• [Presentation] インドネシアにおけるＢ型肝炎ウイルス感染に関連する宿主因子の検討 (2016)
  • Author(s): 矢野 嘉彦
  • Organizer: 第20回日本肝臓学会大会
  • Place of Presentation: 神戸