Data mining analysis for the investigation of clinical features of chronic hepatitis C

• Project/Area Number: 20590768
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: University of Yamanashi
• Principal Investigator: KUROSAKI Masayuki University of Yamanashi, 大学院・医学工学総合研究部, 医学研究員 (10280976)
• Co-Investigator(Kenkyū-buntansha): IZUMI Namiki 山梨大学, 大学院・医学工学総合研究部, 医学研究員 (20397300) ; ENOMOTO Nobuyuki 山梨大学, 大学院・医学工学総合研究部, 教授 (20251530) ; ASAHINA Yasuhiro 山梨大学, 大学院・医学工学総合研究部, 医学研究員 (00422692)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: データ・マイニング / C型肝炎 / 肝がん / インターフェロン / 個別化診療 / データマイニング / C型慢性肝炎

Research Abstract

We have analyzed factors that are predictive of response to peg-interferon plus ribavirin in chronic hepatitis C using data mining method. We found that hepatic steatosis, lower LDL-cholesterol level, higher glucose level and higher GGT level was predictive of poor virological response during the early treatment period. The HCV sequences in the ISDR and Core 70 was predictors of response independently of other factors. In 2009, a SNP near the IL28B was found to be most closely associated with the response to interferon therapy. We found that while IL28B was associated with the probability of viral decline, ISDR was a predictor of SVR independently of IL28B since ISDR was related to relapse of hepatitis. In the search for the factors associated with HCC development, lower albumin, higher FIB-4 index, hepatic steatosis and hyperglycemia was identified as a significant predictor. Hyperglycemia and hepatic steatosis was related to HCC development independent of liver fibrosis. Whether thee metabolic features could be the target for therapeutic intervention to reduce the incidence of HCC awaits further investigation.

Research Products

• [Journal Article] Changes in hepatitis C viral load during first 14 days can predict the undetectable time point of serum viral load by pegylated interferon and ribavirin therapy. (2011)
  • Author(s): Itakura J, Asahina Y, Tamaki N, Hirayama I, Yasui Y, Tanaka T, Sato M, Ueda K, Kuzuya T, Tsuchiya K, Nakanishi H, Kurosaki M, Gabriel GS, Schneider GJ, Izumi N.
  • Journal Title: Hepatol Res 41 Pages: 217-224
  • Peer Reviewed
• [Journal Article] Association of IL28B polymorphism with response to pegylated-interferon alpha plus ribavirin combination therapy in patients with chronic genotype 2 hepatitis C. (2011)
  • Author(s): Sakamoto N, Kurosaki M, et al.
  • Journal Title: J Medical Virol 25 Pages: 22038-22038
  • Peer Reviewed
• [Journal Article] Pretreatment Prediction of Response to Pegylated-Interferon Plus Ribavirin for Chronic Hepatitis C using Genetic Polymorphism in IL28B and Viral Factors. (2011)
  • Author(s): Kurosaki M, Tanaka Y., Nishida N., Sakamoto N,, Enomoto, N., Honda, M.、Sugiyama M., Matsuura, K., Sugauchi, K., Asahina Y, Nakagawa, M., Watanabe, M., et al.
  • Journal Title: J Hepatol
  • Peer Reviewed
• [Journal Article] Sequences in the Interferon Sensitivity Determining Region and Core Region of Hepatitis C Virus Impact Pretreatment Prediction of Response to Peg-interferon Plus Ribavirin : Data Mining Analysis. (2011)
  • Author(s): Kurosaki M, Sakamoto N, Iwasaki M, Sakamoto M, Suzuki Y, Hiramatsu N, Sugauchi F, Tamori A, Nakagawa M, Izumi N.
  • Journal Title: J Med Virol 83(3) Pages: 445-452
  • Peer Reviewed
• [Journal Article] Sequences in the Interferon Sensitivity Determining Region and Core Region of Hepatitis C Virus Impact Pretreatment Prediction of Response to Peg-interferon Plus Ribavirin : Data Mining Analysis. (2011)
  • Author(s): Kurosaki M, et al
  • Journal Title: J Med Virol Volume: 83 Pages: 445-452
  • Peer Reviewed
• [Journal Article] Pretreatment Prediction of Response to Pegylated-Interferon Plus Ribavirin for Chronic Hepatitis C using Genetic Polymorphism in IL28B and Viral Factors. (2011)
  • Author(s): Kurosaki M, et al
  • Journal Title: J Hepatol Volume: 54 Pages: 439-448
  • Peer Reviewed
• [Journal Article] Pretreatment prediction of response to peginterferon plus ribavirin therapy in genotype 1 chronic hepatitis C usmg data mining analysis. (2011)
  • Author(s): Kurosaki M, et al
  • Journal Title: J Gastroenterol Volume: (In press)
  • Peer Reviewed
• [Journal Article] Predictors of virological response to a combination therapy with pegylated interferon plus ribavirin including virus and host factors. (2010)
  • Author(s): Izumi N, Asahina Y, Kurosaki M.
  • Journal Title: Hepat Res Treat 703602 Pages: 703602-703602
  • Peer Reviewed
• [Journal Article] A Predictive Model of Response to Peginterferon Ribavirin in Chronic Hepatitis C using Classification and Regression Tree Analysis. (2010)
  • Author(s): Kurosaki M., Matsunaga K., Hirayama I., Tanaka T., Sato M., Yasui Y., et al.
  • Journal Title: Hepatol Res. 40 Pages: 251-260
  • NAID: 10027407678
  • Peer Reviewed
• [Journal Article] Hepatic steatosis in chronic hepatitis C is a significant risk factor for developing hepatocellular carcinoma independent of age, sex, obesity (2010)
  • Author(s): Kurosaki M., Hosokawa, T., Matsunaga, K., Hirayama, I., Tanaka, T., Sato, M., Yasui, Y., Tamaki, N., Ueda, K.,Tsuchiya, K., Kuzuya, T., Nakanishi, H., Itakura, J., Takahashi, Y, Asahina, Y, Enomoto, N, Izumi, N
  • Journal Title: fibrosis stage and response to interferon therapy Hepatol Res. 40 Pages: 870-877
  • Peer Reviewed
• [Journal Article] Effect of aging on risk for hepatocellular carcinoma in chronic hepatitis C virus infection. (2010)
  • Author(s): Asahina Y, Tsuchiya K, Tamaki N, Hirayama I, Tanaka T, Sato M, Yasui Y, Hosokawa T, Ueda K, Kuzuya T, Nakanishi H, Itakura J, Takahashi Y, Kurosaki M, Enomoto N, Izumi N.
  • Journal Title: Hepatology 52 Pages: 518-527
  • Peer Reviewed
• [Journal Article] Predictive Model of Response to Peginterferon Ribavirin in Chronic Hepatitis C using Classification and Regression Tree Analysis (2010)
  • Author(s): Kurosaki M, et al.
  • Journal Title: Hepatol Res 40 Pages: 251-260
  • NAID: 10027407678
  • Peer Reviewed
• [Journal Article] Reproducibility and usability of chronic virus infection model using agent-based simulation; comparing with a mathematical model. (2009)
  • Author(s): Itakura J., Kurosaki M, Itakura Y, Maekawa S., Asahina Y, Izumi N, et al.
  • Journal Title: Biosystems. 12 Pages: 12-12
  • Peer Reviewed
• [Journal Article] Reproducibility and usability of chronic virus infection model using agent-based simulation ; comparing with a mathematical model (2009)
  • Author(s): Itakura J., et al.
  • Journal Title: Biosystems 99 Pages: 70-78
  • Peer Reviewed
• [Journal Article] Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C. (2009)
  • Author(s): Tanaka Y, et al.
  • Journal Title: Nat Genet 41 Pages: 1105-1109
  • Peer Reviewed
• [Journal Article] The presence of steatosis and elevation of alanine aminotransferase levels are associated with fibrosis progression in chronic hepatitis C with non-response to interferon therapy. (2008)
  • Author(s): Kurosaki M, Matsunaga K, Hirayama I, Tanaka T, Sato M, Komatsu N, Umeda N, et al.
  • Journal Title: J Hepatol 48 Pages: 736-742
  • Peer Reviewed
• [Journal Article] External validation of FIB-4 : diagnostic accuracy is limited in elderly (2008)
  • Author(s): Kurosaki M, Izumi N
  • Journal Title: populations.Hepatology 47 Pages: 352-353
  • Peer Reviewed
• [Journal Article] Miyake S Potential relevance of cytoplasmic viral sensors and related regulators involving innate immunity in antiviral response. (2008)
  • Author(s): Asahina Y, Izumi N, Hirayama I, Tanaka T, Sato M, Yasui Y, Komatsu N, Umeda N, Hosokawa T, Ueda K, Tsuchiya K, Nakanishi H, Itakura J, Kurosaki M, Enomoto N, Tasaka M, Sakamoto N,
  • Journal Title: Gastroenterology 134 Pages: 1396-1405
  • Peer Reviewed
• [Journal Article] The presence of steatosis and elevation of alanine aminotransferase levels are associated with fibrosis progression chronic hepatitis C with non-response to interferon therapy. (2008)
  • Author(s): Kurosaki M, etal.
  • Journal Title: Journal of Hepatology 48(5) Pages: 736-42
  • Peer Reviewed
• [Journal Article] External validation of FIB-4 : diagnostic accuracy is limited in elderly populatins. (2008)
  • Author(s): Kurosaki M, etal.
  • Journal Title: Hepatology 47(1) Pages: 352-3
  • Peer Reviewed
• [Journal Article] 【NASH起因発癌のエビデンス】NASH発癌の危険因子 (2008)
  • Author(s): 細川貴範, 黒崎雅之
  • Journal Title: 消化器科 48(1) Pages: 128-131
• [Presentation] Prediction of Response to Pegylated-Interferon for Chronic Hepatitis C : Impact of SNPs near the IL28B gene and Mutations in the ISDR of HCV Revealed by Data Mining Analysis. (2010)
  • Author(s): Kurosaki M, et al.
  • Organizer: 米国肝臓学会
  • Place of Presentation: Boston
  • Year and Date: 2010-11-01
• [Presentation] Prediction of Response to Pegylated-Interferon for Chronic Hepatitis C : Impact of SNPs near the IL28B gene and Mutations in the ISDR of HCV Revealed by Data Mining Analysis. (2010)
  • Author(s): Kurosaki M, et al
  • Organizer: 米国肝臓学会
  • Place of Presentation: 米国ボストン州
  • Year and Date: 2010-10-31
• [Presentation] Predictive value of FIB-4 index for hepatocelular carcinoma development in chronic hepatitis (2009)
  • Author(s): Kurosaki M, et al.
  • Organizer: C米国肝臓学会
  • Place of Presentation: Boston
  • Year and Date: 2009-10-30
• [Presentation] Impact of Mutations in ISDR and Core Region of HCV on Pretreatment Prediction of Sustained Virological Response to Pegylated-interferon Plus Ribavirin Therapy ; Classification and Regression Tree Analysis (2009)
  • Author(s): Kurosaki M, et al.
  • Organizer: 第16回国際C型肝炎ウイルスおよび関連ウイルスシンポジュウム
  • Place of Presentation: Nice
  • Year and Date: 2009-10-06
• [Presentation] Impact of Mutations in ISDR and Core Region of HCV on Pretreatment Prediction of Sustained Virological Response to Pegylated-interferon Plus Ribavirin Therapy : Classification and Regression Tree Analysis (2009)
  • Author(s): Kurosaki M, et al
  • Organizer: International Symposium on HCV and related viruses
  • Place of Presentation: Nice, France
  • Year and Date: 2009-10-03
• [Presentation] Peginterferon/ribavirin併用療法の治療前効果予測データマイニング解析による予測アルゴリズムの構築と検証 (2008)
  • Author(s): 黒崎雅之
  • Organizer: 肝臓学会
  • Place of Presentation: 愛媛県民文化会館
  • Year and Date: 2008-06-06