Experimental and clinical studies on the effects of L-carnitine in minimal hepatic encephalopathy

• Project/Area Number: 25461009
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Iwate Medical University
• Principal Investigator: Suzuki kazuyuki 岩手医科大学, 医学部, 名誉教授 (00137499)
• Co-Investigator(Renkei-kenkyūsha): Sawara Kei 岩手医科大学, 内科学講座消化器内科肝臓分野, 助教 (40405816) ; Wang Ting 岩手医科大学, 内科学講座消化器内科肝臓分野, 助教 (70416171)
• Research Collaborator: Kakisaka Keisuke 岩手医科大学, 内科学講座消化器内科肝臓分野, 助教 ; Kuroda Hidekatsu 岩手医科大学, 内科学講座消化器内科肝臓分野, 助教 ; Kato Akinobu 盛岡市立病院, 院長
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: カルニチン / ミニマル肝性脳症 / 肝硬変 / アンモニア / 血清遊離脂肪酸 / アストロサイト / 肝性脳症

Outline of Final Research Achievements

Clinical study: The levels of serum carnitine in patients with liver cirrhosis (LC) were almost within normal range. Approximately 11% of LC patients had serum CA levels < 45μmol/L. The serum CA levels did not correlate with severity of liver damage and the existence of MHE, but were closely associated with renal dysfunction. The serum free fatty acid levels strongly correlated with serum Ac-CA levels and the Ac-CA to T-CA ratio. The improvement of hyperammonemia was observed 46% of LC patients administrated L-CA.
Experimental study: Cell viability and intracellular total ROS and LDH leakage of human astrocytes were significantly increased after treatment with NH4Cl, while cotreatment with L-CA significantly improved these cytotoxic changes. In metabolome analysis, although the expression levels of the all essential amino acids showed high in the NH4Cl-treated cells, these changes were improved in cotreatment with L-CA. L-CA may protect astrocytes against the toxic effects of NH4Cl.

Research Products

• [Journal Article] Brain metabolism in minimal hepatic encephalopathy assessed by 3.0-Tesla magnetic resonance spectroscopy (2016)
  • Author(s): Kooka Yohei, Sawara Kei, Endo Rujin, Kato Akinobu, Suzuki Kazuyuki, Takikawa Yasuhiro.
  • Journal Title: Hepatol Reserch Volume: 46 Issue: 4 Pages: 269-76
  • DOI: 10.1111/hepr.12519
  • Peer Reviewed
• [Journal Article] 肝硬変におけるミニマル肝性脳症の合併率とその予測因子に関する検討：高齢者と非高齢者での健康 (2016)
  • Author(s): 鈴木一幸、佐原圭、小岡洋平、黒田英克、遠藤龍人、滝川康裕、加藤章信
  • Journal Title: 日本高齢消化器病学会誌 Volume: １８ Pages: 58-63
  • Peer Reviewed
• [Journal Article] 高齢肝硬変患者の蛋白・エネルギー代謝異常の特徴 (2016)
  • Author(s): 鈴木一幸、永井田優衣、佐原圭、遠藤啓、遠藤龍人、黒田英克、滝川康裕、加藤章信
  • Journal Title: 日本高齢消化器病学会誌 Volume: １８ Pages: 32-35
  • Peer Reviewed
• [Journal Article] Branched-chain amino acids prevent hepatocarcinogenesis and prolong survival of patients with cirrhosis (2015)
  • Author(s): Kawaguchi T, Shiraishi K, Ito T, Suzui K, Koreeda C, Ohtake T, Iwasa M, Tokumoto Y, Endo R, Kawamura N, Shiraki M, Habu D, Tsuruta S, Miwa Y, Kawaguchi A, Kakuma T, Sakai H, Kawada N, Hanai T, Takahashi S, Kato A, Onji M, Takei Y, Kohgo Y, Seki T, Tamano M, Katayama K, Mine T, Sata M, Moriwaki H, and Suzuki K
  • Journal Title: Clin Gastroenterol Hepatol Volume: 12 Issue: 6 Pages: 1012-1018
  • DOI: 10.1016/j.cgh.2013.08.050
  • Peer Reviewed
• [Journal Article] Proliferation of mouse liver stem/progenitor cells induced by plasma from (2014)
  • Author(s): Wang T, Takikawa Y, Watanabe A, Kakisaka K, Oigawa K, Miyamoto Y, Suzuki K.
  • Journal Title: J Gastroenterol. Volume: 49 Issue: 12 Pages: 1557-1566
  • DOI: 10.1007/s00535-013-0927-6
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Open-labeled randomized controlled trial to compare diuretic therapy with recombinant human serum albumin and diuretic therapy for therapeutic treatment of ascites in patients with advanced liver cirrhosis: An exploratory trial. (2014)
  • Author(s): Nakamura T, Sata M, Suzuki K, Moriwaki H, Fukui H, Fujiyama S, Imawari M
  • Journal Title: Hepatology Research Volume: 44 Issue: 5 Pages: 502-14
  • DOI: 10.1111/hepr.12142
  • Peer Reviewed / Open Access
• [Journal Article] Effects of subcutaneous administration of pegylated interferon alpha-2b on the behavior and the cytokine levels od serum and brain in rats (2014)
  • Author(s): Yoshida Y and Suzuki K
  • Journal Title: JIMA Volume: 66 Pages: 101-112
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 肝硬変治療の進歩(4)分岐鎖アミノ酸製剤による治療効果 (2014)
  • Author(s): 遠藤龍人、佐原 圭、遠藤 啓、滝川康裕、加藤章信、鈴木一幸
  • Journal Title: 臨牀消化器内科 Volume: 29 Pages: 447-452
  • Open Access
• [Journal Article] 肝疾患の栄養管理 (2014)
  • Author(s): 遠藤龍人、佐原 圭、遠藤 啓、滝川康裕、鈴木一幸
  • Journal Title: 臨牀消化器内科 Volume: 29 Pages: 1119-1127
  • Open Access
• [Journal Article] Effect of zinc on liver cirrhosis with hyperammonemia: A preliminary randomized, placebo-controlled, double-blind trial (2014)
  • Author(s): Katayama K, Saito M, Kawaguchi T, Endo R, Sawara K, Nishiguchi S, Kato A, Kohgo H, Suzuki K, Sakaida I, Ueno Y, Habu D, Ito T, Moriwaki H, Suzuki K
  • Journal Title: Nutrition Volume: 30 Pages: 1409-1419
  • Peer Reviewed / Open Access
• [Journal Article] Usefulness and accuracy of the international normalized ratio and activity percent of prothrombin time in patients with liver disease. (2014)
  • Author(s): Takikawa Y, Harada M, Wang T, Suzuki K.
  • Journal Title: Hepatol Res. Volume: 44 Issue: 1 Pages: 92-101
  • DOI: 10.1111/hepr.12093
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 肝疾患 肝性脳症 (2014)
  • Author(s): 鈴木一幸、佐原 圭、遠藤龍人、滝川康裕
  • Journal Title: 日本臨牀 内科疾患にみられる神経障害（疾患）肝・腎・肺疾患 Volume: 別冊 Pages: 350-353
  • Open Access
• [Journal Article] Nutritional management contributes to improvement in minimal hepatic encephalopathy and quality of life in patients with liver cirrhosis: A preliminary, prospective, open-label study (2013)
  • Author(s): Akinobu Kato
  • Journal Title: Hepatology Research Volume: 43 Issue: 5 Pages: 452-458
  • DOI: 10.1111/j.1872-034x.2012.01092.x
  • NAID: 10031183476
  • Peer Reviewed
• [Journal Article] 血清遊離脂肪酸濃度は肝硬変における血清カルニチン動態を反映する (2013)
  • Author(s): 鈴木一幸
  • Journal Title: 肝臓 Volume: 54 Pages: 796-797
  • NAID: 130003384490
  • Peer Reviewed
• [Presentation] L-carnitine prevents ammonia-induced cytotoxicity on human astrocytes: Results of metabolome analysis (2015)
  • Author(s): Kazuyuki Suzuki, Ting Wang, Keisuke Kakisaka, Kei Sawara, Miho Onodera, Hidekatsu Kuroda, Ryujin Endo, Akinobu Kato, and Yasuhiro Takikawa
  • Organizer: ASSLD
  • Place of Presentation: Chicago, USA
  • Year and Date: 2015-10-16
  • Int'l Joint Research
• [Presentation] 肝硬変におけるミニマル肝性脳症の罹患率とその診断的予測因子の検索 (2015)
  • Author(s): 小野寺美緒、鈴木一幸、黒田英克、小岡洋平、佐原 圭、王 挺、及川隆喜、遠藤龍人、滝川康裕、加藤章信
  • Organizer: 第51回日本肝臓学会総会
  • Place of Presentation: 熊本市
  • Year and Date: 2015-05-21 – 2015-05-22
• [Book] 「内科」2016年4月増大号特集：、症例から学ぶ内科疾患の診断・治療ピットホール 第2章 消化器「肝硬変」 (2016)
  • Author(s): 佐藤寛毅、滝川康裕、鈴木一幸
  • Total Pages: 4
  • Publisher: 南江堂
• [Book] 新しい診断と治療のABC 44「 肝硬変」改訂第2版 第4章 管理・治療 薬物療法２．高アンモニア血腫治療の進歩 (2015)
  • Author(s): 鈴木一幸、佐原圭、小岡洋平、吉田雄一、小野寺美緒、遠藤龍人、滝川康裕、加藤章信
  • Total Pages: 11
  • Publisher: 最新医学社
• [Book] 最新医学・別冊 新しい診断と治療のABC 肝硬変改定第２版 第４章 管理・治療 薬物療法２．高アンモニア血症治療の進歩 (2013)
  • Author(s): 鈴木一幸
  • Total Pages: 11
  • Publisher: 最新医学社