Analysis of the polymerase gene of HBV virus

• Project/Area Number: 18590725
• 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, Deparment of Research Interdisciplinary, Graduate School of Medicine and Engineering, Research Fellow (10280976)
• Co-Investigator(Kenkyū-buntansha): IZUMI Namiki University of Yamanashi, Deparment of Research Interdisciplinary, Graduate School of Medicine and Engineering, Research Fellow (20397300) ; ENOMOTO Nobuyuki University of Yamanashi, Deparment of Research Interdisciplinary, Graduate School of Medicine and Engineering, Professor (20251530)
• Project Period (FY): 2006 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000); Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
• Keywords: Henatitis B virus / Polymerase gene / mutation / Lamivudine / breakthrough hepatitis / Polymerase遺伝子 / domain B / domain A / polymerase遺伝子

Research Abstract

The mutational pattern of the polymerase gene in HBV carriers under lamivudine (LAM) treatment was examined. Mutation in the rt204 of the polymerase gene (so called YMDD motif) was detected in 28% of patients with persistently negative for HBVDNA. These latent mutations without clinically obvious breakthrough, progressed to overt viral breakthrough in 80% of patients within 2 years of LAM treatment, 33% of patients with 3 to 5 years of LAM treatment and 0% of patients with 5 or more years of LAM treatment In addition some patients had mutation in the rt180, which was positively correlated with subsequent development of viral breakthrough. Mutations in rt80 was also frequently observed but was not related to clinical outcomes.
In the analysis of patients with long term entecavir therapy for LAM resistant virus, those without clearance of HBV at week 24 had higher risk of developing resistant virus. The rt204V mutation may be related to higher risk of resistance, which need further investigations.

Research Products

• [Journal Article] The presence of steatosis and elevation of alanine aminotransferase level are associated with fibrosis progression in chronic hepatitis C with non-response to interferon therapy (2008)
  • Author(s): KurosakiM, et. al.
  • Journal Title: J Hepatology (In press)
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] External validation of FIB-4: diagnostic accuracy is limited in elderly populations (2008)
  • Author(s): KurosakiM, et. al.
  • Journal Title: Hepatology 47 Pages: 357-358
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] The presence of steatosis and elevation of alanine aminotransferase level 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., Hosokawa, T., Ueda, K., Tsuchiya, K., Nakanishi, H., Itakura, J., Asahina, Y., Miyake, S., Enomoto, N., Izumi, N
  • Journal Title: Journal of Hepatology 48 Pages: 736-736
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] External validation of FIB-4 : diagnostic accuracy is limited in elderly populations (2008)
  • Author(s): Kurosaki, M., Izumi, N
  • Journal Title: Hepatology 47 Pages: 352-352
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Pharmacokinetics and enhanced PKR response in patients with chronic hepatitis C treated with pegylated interferon alpha-2b and ribavirin (2007)
  • Author(s): Asahina Y, et. al.
  • Journal Title: J Viral Hepat 14 Pages: 396-403
  • Peer Reviewed
• [Journal Article] Negative regulation of intracellular hepatitis c virus replication by interferon regulatory factor 3 (2006)
  • Author(s): Yamashito T et al.
  • Journal Title: J Gastroenterology 41 Pages: 750-7
• [Journal Article] Pegylated interferon-associated retinopathy in chronic hepatitis C patients (2006)
  • Author(s): Ogata H et al.
  • Journal Title: Jpn J Ophthaklmol 50 Pages: 293-4
• [Journal Article] Optimal timing of interferon treatment for acute hepatitis c (2006)
  • Author(s): Kuroswaki M et al.
  • Journal Title: Hepatol Res 34 Pages: 1-2
• [Journal Article] Expressional screening of interferon-stimulated genes for antiviral activity against hepatitis Cvirus replication (2006)
  • Author(s): Itsui Y et al.
  • Journal Title: J Viral Hepat 13 Pages: 690-700
• [Journal Article] B型慢性肝炎に対するラミブジン治療における寛解維持効果 (2006)
  • Author(s): 黒崎雅之
  • Journal Title: 消化器科 42 Pages: 400-406
• [Journal Article] 抗HBV療法 (2006)
  • Author(s): 黒崎雅之
  • Journal Title: 消化器の臨床 9 Pages: 289-297
• [Presentation] パネルディスカッション:B型慢性肝炎治療の新展開 B型慢性肝炎に対する核酸アナログ製剤の治療成績 (2007)
  • Author(s): 黒崎雅之、泉並木、三宅祥三
  • Organizer: 第11回日本肝臓学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2007-10-19
• [Presentation] データマイニング解析による発癌予測 C型慢性肝炎におけるsteatosisは、年齢、肝線維化、interferon治療効果と独立した発癌危険因子であることの証明 (2007)
  • Author(s): 黒崎雅之、泉並木、他
  • Organizer: 第43回日本肝臓学会総会
  • Place of Presentation: 東京
  • Year and Date: 2007-06-01
• [Presentation] 発癌からみたALT基準値内のC型肝炎治療ガイドラインの検証 ALT、血小板は発癌予測因子であり、IFN治療によるALT,AFPの制御は発癌リスクを減少させる (2007)
  • Author(s): 黒崎雅之、泉並木、他
  • Organizer: 第43回日本肝臓学会総会
  • Place of Presentation: 東京
  • Year and Date: 2007-05-31
• [Presentation] ワークショップ:ウイルス肝炎の新しい治療法 データマイニング解析によるpeginteferon/ribavirin併用療法の治療効果予測 (2007)
  • Author(s): 黒崎雅之、泉並木、他
  • Organizer: 第43回日本肝臓学会総会
  • Place of Presentation: 東京
  • Year and Date: 2007-05-31