Biomarker for hepatocarcinogenesis in diabetic patients

• Project/Area Number: 17K09426
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Hiroshima University
• Principal Investigator: Aikata Hiroshi 広島大学, 医系科学研究科(医), 准教授 (30403512)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2017: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 肝癌 / 生活習慣病 / 非B型非C型 / 糖尿病

Outline of Final Research Achievements

The number of patients with hepatitis B virus- and hepatitis C virus-negative liver cancer tended to increase, and it was revealed that many of these patients were associated with diabetes and lifestyle-related diseases. Background About 60% of cases were classified as non-alcoholic steatohepatitis, alcoholic hepatitis, and cirrhosis. On the other hand, many of these patients have high Fib4 index, which is one of the indicators of liver fibrosis markers, and can be a useful index in the screening of a high-risk group for liver cancer in patients with diabetes and lifestyle-related diseases.

Academic Significance and Societal Importance of the Research Achievements

本邦における糖尿病、脂肪肝など生活習慣病を有している患者は、増加傾向にある。近年、これらの生活習慣病を背景とした脂肪性肝疾患のみならず、肝癌の増加が社会問題となっている、これらの生活習慣病患者において肝癌高リスクグループのスクリーニング法は未だ確立されていないが、本研究において、肝線維化マーカーの指標の一つとされるFib4index、有用な指標となることが示唆された。

Research Products

• [Journal Article] Diminished hepatic IFN response following HCV clearance triggers HBV reactivation in coinfection. (2020)
  • Author(s): Cheng X, Uchida T, Xia Y, Umarova R, Liu CJ, Chen PJ, Gaggar A, Suri V, Mucke MM, Vermehren J, Zeuzem S, Teraoka Y, Osawa M, Aikata H, Tsuji K, Mori N, Hige S, Karino Y, Imamura M, Chayama K, Liang TJ.
  • Journal Title: J Clin Invest. Volume: - Issue: 6 Pages: 3205-3220
  • DOI: 10.1172/jci135616
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Classification of primary liver cancer with immunosuppression mechanisms and correlation with genomic alterations. (2020)
  • Author(s): Fujita M, Yamaguchi R, Hasegawa T, Shimada S, Arihiro K, Hayashi S, Maejima K, Nakano K, Fujimoto A, Ono A, Aikata H, Ueno M, Hayami S, Tanaka H, Miyano S, Yamaue H, Chayama K, Kakimi K, Tanaka S, Imoto S, Nakagawa H.
  • Journal Title: EBioMedicine Volume: 53 Pages: 102659-102659
  • DOI: 10.1016/j.ebiom.2020.102659
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Incidence of microsatellite instability-high hepatocellular carcinoma among Japanese patients and response to pembrolizumab. (2020)
  • Author(s): Kawaoka T, Ando Y, Yamauchi M, Suehiro Y, Yamaoka K, Kosaka Y, Fuji Y, Uchikawa S, Morio K, Fujino H, Nakahara T, Ono A, Murakami E, Takahashi S, Tsuge M, Hiramatsu A, Imamura M, Chayama K, Aikata H.
  • Journal Title: Hepatol Res. Volume: - Issue: 7 Pages: 885-888
  • DOI: 10.1111/hepr.13496
  • Peer Reviewed / Open Access
• [Journal Article] Hepatic arterial infusion chemotherapy followed by sorafenib in patients with advanced hepatocellular carcinoma (HICS 55): an open label, non-comparative, phase II trial. (2018)
  • Author(s): Hatooka M, Kawaoka T, Aikata H, Inagaki Y, Morio K, Nakahara T, Murakami E, Tsuge M, Hiramatsu A, Imamura M, Kawakami Y, Awai K, Masaki K, Waki K, Kohno H, Kohno H, Moriya T, Nagaoki Y, Tamura T, Amano H, Katamura Y, Chayama K.
  • Journal Title: BMC Cancer. Volume: 18 Issue: 1 Pages: 633-633
  • DOI: 10.1186/s12885-018-4519-y
  • NAID: 120006559420
  • Peer Reviewed / Open Access
• [Journal Article] Comparison of hepatic arterial infusion chemotherapy between 5-fluorouracil-based continuous infusion chemotherapy and low-dose cisplatin monotherapy for advanced hepatocellular carcinoma. (2018)
  • Author(s): Kawaoka T, Aikata H, Kobayashi T, Uchikawa S, Ohya K, Kodama K, Nishida Y, Daijo K, Osawa M, Teraoka Y, Inagaki Y, Honda F, Hatooka M, Morio K, Morio R, Fujino H, Nakahara T, Murakami E, Tsuge M, Hiramatsu A, Imamura M, Kawakami Y, Baba Y, Awai K, Chayama K.
  • Journal Title: Hepatol Res. Volume: 48 Issue: 13 Pages: 1118-1130
  • DOI: 10.1111/hepr.13232
  • Peer Reviewed
• [Journal Article] Clinical outcomes of sorafenib treatment failure for advanced hepatocellular carcinoma and candidates for regorafenib treatment in real-world practice. (2018)
  • Author(s): Uchikawa S, Kawaoka T, Aikata H, Kodama K, Nishida Y, Inagaki Y, Hatooka M, Morio K, Nakahara T, Murakami E, Hiramatsu A, Tsuge M, Imamura M, Kawakami Y, Chayama K.
  • Journal Title: Hepatol Res. Volume: 48 Issue: 10 Pages: 814-820
  • DOI: 10.1111/hepr.13180
  • Peer Reviewed
• [Journal Article] Comparison of clinical outcome of hepatic arterial infusion chemotherapy and sorafenib for advanced hepatocellular carcinoma according to macrovascular invasion and transcatheter arterial chemoembolization refractory status. (2018)
  • Author(s): Kodama K, Kawaoka T, Aikata H, Uchikawa S, Inagaki Y, Hatooka M, Morio K, Nakahara T, Murakami E, Tsuge M, Hiramatsu A, Imamura M, Kawakami Y, Masaki K, Honda Y, Mori N, Takaki S, Tsuji K, Kohno H, Kohno H, Moriya T, Nonaka M, Hyogo H, Aisaka Y, Chayama K.
  • Journal Title: J Gastroenterol Hepatol. Volume: 33 Issue: 10 Pages: 1780-1786
  • DOI: 10.1111/jgh.14152
  • Peer Reviewed
• [Journal Article] Comparison of Outcome of Hepatic Arterial Infusion Chemotherapy Combined with Radiotherapy and Sorafenib for Advanced Hepatocellular Carcinoma Patients with Major Portal Vein Tumor Thrombosis. (2018)
  • Author(s): Kodama K, Kawaoka T, Aikata H, Uchikawa S, Nishida Y, Inagaki Y, Hatooka M, Morio K, Nakahara T, Murakami E, Tsuge M, Hiramatsu A, Imamura M, Kawakami Y, Masaki K, Honda Y, Mori N, Takaki S, Tsuji K, Kohno H, Kohno H, Moriya T, Nonaka M, Hyogo H, Aisaka Y, Kimura T, Nagata Y, Chayama K.
  • Journal Title: Oncology Volume: 94 Issue: 4 Pages: 215-222
  • DOI: 10.1159/000486483
  • Peer Reviewed
• [Journal Article] Risk factors for exacerbation of gastroesophageal varices and portosystemic encephalopathy during treatment with nucleos(t)ide analogs for hepatitis B virus-related cirrhosis. (2018)
  • Author(s): Nagaoki Y, Aikata H, Daijyo K, Teraoka Y, Honda F, Nakamura Y, Hatooka M, Morio K, Fujino H, Nakahara T, Kawaoka T, Miki D, Tsuge M, Hiramatsu A, Imamura M, Kawakami Y, Ochi H, Chayama K.
  • Journal Title: Hepatol Res Volume: 48 Issue: 4 Pages: 264-274
  • DOI: 10.1111/hepr.12996
  • Peer Reviewed
• [Presentation] 非B非C型肝細胞癌の背景因子と予後に関する検討 (2019)
  • Author(s): 長沖祐子，相方浩，茶山一彰
  • Organizer: 第55回日本肝癌研究会
• [Presentation] 非B非C型慢性肝疾患患者のアルコール摂取量で群別化した比較検討 (2018)
  • Author(s): 村上英介，相方浩，茶山一彰
  • Organizer: 第104回日本消化器病学会総会
• [Presentation] 非B非C型肝細胞癌の背景因子とリスク因子に関する検討 (2018)
  • Author(s): 長沖祐子，相方浩，茶山一彰
  • Organizer: 第54回日本肝臓学会総会
• [Presentation] 非B非C型肝細胞癌の背景因子と予後に関する検討 (2018)
  • Author(s): 長沖祐子，相方浩，茶山一彰
  • Organizer: 第54回日本肝癌研究会
• [Presentation] 2型糖尿病を合併する非B非C肝癌の臨床的特徴の解析 (2018)
  • Author(s): 村上英介，相方浩，茶山一彰
  • Organizer: JDDW2018
• [Presentation] 非B非C型肝細胞癌の背景因子と予後に関する検討 (2018)
  • Author(s): 長沖祐子、相方浩、茶山一彰
  • Organizer: 第54回日本肝癌研究会