Tailor-made treatment for prevention of hepatitis after liver transplantation.

• Project/Area Number: 24591876
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Mie University
• Principal Investigator: Usui Masanobu 三重大学, 医学部附属病院, 准教授 (10378341)
• Co-Investigator(Kenkyū-buntansha): 杉本 和史 三重大学, 医学部附属病院, 講師 (60378370)
• Project Period (FY): 2012-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2016: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000); Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2014: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 肝移植 / 肝炎ウィルス / テーラーメード治療 / B型肝炎 / C型肝炎

Outline of Final Research Achievements

For the patients undergoing liver transplantation for hepatitis B virus (HBV)-related diseases, hepatitis B immunoglobulin (HBIG) should be administered to prevent reinfection. Because HBIG is highly expensive, an alternative strategy using HBV vaccination has been made in an attempt to discontinue use of HBIG. The ratio of male/female was 13/1 (median age: 55 years; range: 37 years to 67 years). The median follow-up time was 102 months (range: approximately 14 months to 148 months). All 14 patients were free of HBV recurrence. HBIG-free status could be achieved in 9 patients (64.3%) during the treatment period for more than 50 months after beginning of HBV vaccination, of whom 5 (35.7%) became HBV vaccine-free. T-cell proliferation was confirmed by fact that the stimulation index ranged from 2.34 to 5.2 in the patients who were HBIG-free.Long-term HBV vaccination after LT is a useful and effective treatment in preventing HBV recurrence, allowing the discontinuation of HBIG treatment.

Research Products

• [Journal Article] Discontinuation of Hepatitis B Immunoglobulin by Long-term Hepatitis B Vaccine Inoculation in Preventing Hepatitis B Recurrence After Liver Transplantation. (2016)
  • Author(s): Usui M, Sugimoto K, Kato H, Murata Y, Tanemura A, Kuriyama N, Azumi Y, Kishiwada M, Mizuno S, Sakurai H, Takei Y, Isaji S.
  • Journal Title: Transplant Proc Volume: 48 Issue: 4 Pages: 1179-1183
  • DOI: 10.1016/j.transproceed.2015.12.110
  • Peer Reviewed
• [Journal Article] Substitution in Amino Acid 70 of Hepatitis C Virus Core Protein Changes the Adipokine Profile via Toll-Like Receptor 2/4 Signaling. (2015)
  • Author(s): Uraki S, Tameda M, Sugimoto K, Shiraki K, Takei Y, Nobori T, Ito M.
  • Journal Title: PLoS One. Volume: 10
  • Peer Reviewed
• [Journal Article] Hypertension and hepatitis C virus infection are strong risk factors for developing late renal dysfunction after living donor liver transplantation: significance of renal biopsy. (2014)
  • Author(s): Fujinaga K, Usui M, Yamamoto N, Ishikawa E, Nakatani A, Kishiwada M, Mizuno S, Sakurai H, Tabata M, Isaji S.
  • Journal Title: Transplant Proc. Volume: 46 Pages: 804-810
  • Peer Reviewed / Open Access
• [Journal Article] The long-term effects of splenectomy and subsequent interferon therapy in patients with HCV-related liver cirrhosis. (2014)
  • Author(s): Inagaki Y, Sugimoto K, Shiraki K, Tameda M, Kusagawa S, Nojiri K, Ogura S, Yamamoto N, Takei Y, Ito M, Mizuno S, Usui M, Sakurai H, Isaji S.
  • Journal Title: Mol Med Rep. Volume: 9 Pages: 487-492
  • Peer Reviewed / Open Access
• [Journal Article] Hypertension and hepatitis C virus infection are strong risk factors for developing late renal dysfunction after living donor liver transplantation: significance of renal biopsy. (2014)
  • Author(s): Fujinaga K, Usui M, Yamamoto N, Ishikawa E, Nakatani A, Kishiwada M, Mizuno S, Sakurai H, Tabata M, Isaji S
  • Journal Title: Transplant Proc. 2014 Apr;46(3):804-10. doi: 10.1016/j.transproceed.2013.11.103. Volume: 46 Pages: 804-810
  • Peer Reviewed
• [Journal Article] Immunological aspects in late phase of living donor liver transplant patients: usefulness of monitoring peripheral blood CD4+ adenosine triphosphate activity. (2013)
  • Author(s): Mizuno S, Muraki Y, Nakatani K, Tanemura A, Kuriyama N, Ohsawa I, Azumi Y, Kishiwada M, Usui M, Sakurai H, Tabata M, Yamamoto N, Yamada T, Shiraki K, Takei Y, Nobori T, Okuda M, Isaji S.
  • Journal Title: Clin Dev Immunol Volume: 2013 Pages: 8-8
  • Peer Reviewed
• [Journal Article] Clinical features and treatment outcome of borderline resectable pancreatic head/body cancer: a multi-institutional survey by the Japanese Society of Pancreatic Surgery. (2013)
  • Author(s): Kato H, Usui M, Isaji S,et al
  • Journal Title: J Hepatobiliary Pancreat Sci Volume: Mar 14. [Epub ahead of print] Issue: 2 Pages: 351-375
  • DOI: 10.1007/s002080100307
  • NAID: 10031194616
  • Peer Reviewed
• [Journal Article] Behavior of ADAMTS13 and Von Willebrand factor levels in patients after living donor liver transplantation. (2013)
  • Author(s): Takahashi N, Wada H, Usui M,et al
  • Journal Title: Thromb Res. Volume: 131(3) Issue: 3 Pages: 225-9
  • DOI: 10.1016/j.thromres.2012.12.002
  • Peer Reviewed
• [Presentation] Discontinuation of hepatitis B immunoglobulin by long-term hepatitis B vaccine inoculation in preventing hepatitis B recurrence after liver transplantation (2015)
  • Author(s): Masanobu Usui, Kazushi Sugimoto, Yasuhiro Murata, Akihiro Tanemura, Naohisa Kuriyama, Masashi Kishiwada, Shugo Mizuno, Hiroyuki Sakurai, Yoshiyuki Takei and Shuji Isaji
  • Organizer: 14th Congress of the Asian Society of Transplantation
  • Place of Presentation: Singapore
  • Year and Date: 2015-08-23
  • Int'l Joint Research
• [Presentation] Influence of angiotensin converting enzyme (ACE) genetic polymorphism on late renal dysfunction after adult-to-adult living donor liver transplantation (2015)
  • Author(s): Toshiki Matsui, Masanobu Usui, Kazuhisa Fujinaga, Kaname Nakatani, Yusuke Iizawa, Hiroyuki Kato, Akihiro Tanemura, Yasuhiro Murata, Yoshinori Azumi, Naohisa Kuriyama, Masashi Kishiwada, Shugo Mizuno, Hiroyuki Sakurai, Shuj Isaji
  • Organizer: 14th Congress of the Asian Society of Transplantation
  • Place of Presentation: Singapore
  • Year and Date: 2015-08-23
  • Int'l Joint Research
• [Presentation] Long-term influence of CYP3A5 gene polymorphism on pharmacokinetics of tacrolimus and patient outcome after living-donor liver transplantation (2015)
  • Author(s): Hiroyuki Kato, Masanobu Usui, Yuichi Muraki, Yusuke Iizawa, Akihiro Tanemura, Yasuhiro Murata, Naohisa Kuriyama, Masashi Kishiwada, Shugo Mizuno, Hiroyuki Sakurai, Masami Tabata, Masahiro Okuda, Junji Nishioka, Kaname Nakatani, Tsutomu Nobori and Shuji Isaji
  • Organizer: 14th Congress of the Asian Society of Transplantation
  • Place of Presentation: Singapore
  • Year and Date: 2015-08-23
  • Int'l Joint Research
• [Presentation] 肝移植後B型肝炎再発予防における，長期継続ワクチン接種によるHBIGからの離脱 (2015)
  • Author(s): 臼井正信，加藤宏之，村田泰洋，種村彰洋，栗山直久，安積良紀，岸和田昌之，水野修吾，櫻井洋至，伊佐地秀司
  • Organizer: 日本肝移植研究会
  • Place of Presentation: ホテルオークラ神戸（兵庫県・神戸市）
  • Year and Date: 2015-05-28
• [Presentation] Impact of an adjuvant hepatitis B vaccination after living donor liver transplantation for hepatitis B-related disease: treatment cost and weaning from hepatitis B hyperimmunoglobulin (2013)
  • Author(s): Usui M
  • Organizer: 第13会アジア移植学会
  • Place of Presentation: 京都
• [Presentation] 生体肝移植後のC型肝炎再発に対するIFN治療の効果予測 ―特にHCV遺伝子変異、IL28B遺伝子多型についてー (2012)
  • Author(s): 臼井 正信
  • Organizer: 日本肝移植研究会
  • Place of Presentation: ホテル日航福岡
• [Remarks] 三重大学 肝胆膵・移植外科
  • URL: http://www.medic.mie-u.ac.jp/hbpt/HBP_and_Transplant_Surgery/Home.html