Details of the Researcher

PHOTO

Masashi Ninomiya
Section
Institute for Excellence in Higher Education
Job title
Assistant Professor
Degree

  • 博士（医学）（東北大学）

Research Areas 1

  • Other / Other /

Papers 181

  1. Comparison of hepatitis B virus genotype B and C patients in Japan in terms of family history and maternal age at birth Peer-reviewed

    Kosuke Sato, Jun Inoue, Takehiro Akahane, Tomoo Kobayashi, Masashi Ninomiya, Akitoshi Sano, Mio Tsuruoka, Masazumi Onuki, Satoko Sawahashi, Keishi Ouchi, Kotaro Doi, Kengo Watanabe, Hirofumi Niitsuma, Atsushi Masamune

    Hepatology Research　2025/02/08

    DOI： 10.1111/hepr.14169 　

  2. Long-read deep sequencing analysis of hepatitis B virus quasispecies in two elderly cases of interspousal transmission. International-journal

    Jun Inoue, Takehiro Akahane, Yutaka Miyazaki, Masashi Ninomiya, Akitoshi Sano, Mio Tsuruoka, Kosuke Sato, Masazumi Onuki, Satoko Sawahashi, Keishi Ouchi, Atsushi Masamune

    Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy　31　(1)　102521-102521　2025/01

    DOI： 10.1016/j.jiac.2024.09.010 　

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    Hepatitis B virus (HBV) can be transmitted within a family, but an interspousal transmission in elderly cases is rare and the change of viral quasispecies during the event is unclear. We experienced two acute hepatitis B males (AH1 and AH2, 67 and 71 years old, respectively) whose HBV was transmitted from their wives with chronic HBV infection (CH1 and CH2, 67 and 66 years old, respectively). To clarify the characteristics of HBV quasispecies in such cases, we performed long-read deep sequencing of HBV preS1/preS2/S domain using samples from the 2 couples. HBV full-genome sequences determined with direct sequencing showed that the HBV sequences belonged to subgenotype B1. AH1 was 98.0-99.2 % identical to CH1, and AH2 was 98.5-99.5 % identical to CH2, whereas the identity between AH1 and AH2 was 96.9 %. The long-read deep sequencing of amplicons including preS1/preS2/S domains with PacBio Sequel IIe showed the numbers of nucleotides with >5 % substitution frequencies in AH1, AH2, CH1 and CH2 were 0 (0 %), 4 (0.31 %), 39 (3.06 %) and 28 (2.20 %), respectively, indicating that CH1 and CH2 were more heterogeneous than AH1 and AH2. From a phylogenetic analysis based on the deep sequencing, minor CH1/CH2 clones that were close to AH1/AH2 clones were considered to be substantially distinct from the major populations in CH1/CH2. The major population formed during chronic infection under the immune pressure might not be suitable to establish new infection and this might be one of the reasons why the transmission had not occurred for a long time after marriage.

  3. 当院における薬物性肝障害・急性肝不全の現状

    土井 耕太郎, 井上 淳, 二宮 匡史, 佐野 晃俊, 鶴岡 未央, 佐藤 公亮, 小貫 真純, 澤橋 里子, 大内 啓志, 渡邊 健吾, 正宗 淳

    肝臓　65　(Suppl.2)　A676-A676　2024/09

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  4. Association of Omega-3 Polyunsaturated Fatty Acids with Sarcopenia in Liver Cirrhosis Patients with Hepatocellular Carcinoma. International-journal

    Akitoshi Sano, Jun Inoue, Eiji Kakazu, Masashi Ninomiya, Mio Tsuruoka, Kosuke Sato, Masazumi Onuki, Satoko Sawahashi, Keishi Ouchi, Atsushi Masamune

    Journal of clinical and translational hepatology　12　(7)　613-624　2024/07/28

    DOI： 10.14218/JCTH.2024.00036 　

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    BACKGROUND AND AIMS: Sarcopenia is associated with the prognosis of patients with liver cirrhosis and hepatocellular carcinoma (HCC). Given their diverse physiological activities, we hypothesized that plasma fatty acids might influence the progression of sarcopenia. This study aimed to clarify the association between fatty acids and sarcopenia in cirrhotic patients with HCC. METHODS: In this single-center retrospective study, we registered 516 cases and analyzed 414 cases of liver cirrhosis and HCC. The skeletal muscle mass index was measured using a transverse computed tomography scan image at the third lumbar vertebra. The cutoff value for sarcopenia followed the criteria set by the Japan Society of Hepatology. Fatty acid concentrations were measured by gas chromatography. RESULTS: Fatty acid levels, particularly omega-3 (n-3) polyunsaturated fatty acid (PUFA), were lower in patients with poor liver function (Child-Pugh grade B/C) and were negatively correlated with the albumin-bilirubin score (p<0.0001). The prognosis of HCC patients with low PUFA levels was significantly worse. Among the different fatty acid fractions, only n-3 PUFAs significantly correlated with skeletal muscle mass index (p=0.0026). In the multivariate analysis, the n-3 PUFA level was an independent variable associated with sarcopenia (p=0.0006). CONCLUSIONS: A low level of n-3 PUFAs was associated with sarcopenia in patients with liver cirrhosis and HCC.

  5. Three consecutive cases of acute liver failure in young women due to acetaminophen overdose: insights into Japanese social issues and transplantation landscape.

    Kotaro Doi, Jun Inoue, Masashi Ninomiya, Akitoshi Sano, Mio Tsuruoka, Kosuke Sato, Masazumi Onuki, Satoko Sawahashi, Keishi Ouchi, Atsushi Masamune

    Clinical journal of gastroenterology　2024/07/26

    DOI： 10.1007/s12328-024-02024-8 　

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    Acetaminophen (APAP) is an over-the-counter (OTC) drug known worldwide for its safety and efficacy. However, in Japan, OTC drug overdose has become a prominent social problem in recent years due to stricter regulations for other drugs, especially among young people, and APAP is an increasing cause of acute liver injury due to overdose. This report describes three consecutive cases of acute liver failure in young women (22, 22 and 19 years old) due to APAP overdose in December 2023. Despite severe liver injury, indicated by high ALT levels and coagulopathy, these cases recovered without requiring liver transplantation. This report discusses three cases of acute liver failure in young Japanese women following APAP overdose, reflecting a national increase in such cases due to increased misuse of OTC drugs and societal factors. Key findings include the need for early treatment with N-acetylcysteine (NAC) and the importance of mental health assessment in the management of overdose patients. The cases underscore the need for prompt team-based care to prevent serious outcomes and highlight the complexity of liver transplantation decisions in Japan, highlighting the need for comprehensive strategies to address the escalating problem of APAP overdose.

  6. Changes in mutations of cell-free DNA and liver tumor tissue in patients with advanced hepatocellular carcinoma before and after introduction of lenvatinib. International-journal

    Mio Tsuruoka, Masashi Ninomiya, Jun Inoue, Tomoaki Iwata, Akitoshi Sano, Kosuke Sato, Masazumi Onuki, Satoko Sawahashi, Atsushi Masamune

    Oncology　2024/07/24

    DOI： 10.1159/000540438 　

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    INTRODUCTION: Cell-free DNA (cfDNA) is expected to contribute to the decision for treatment and prediction of effects with minimally invasion. We investigated the correlation between gene mutations before and after lenvatinib (LEN) treatment and its effectiveness, in order to find advanced hepatocellular carcinoma (HCC) patients who would benefit greatly from the therapy. METHODS: We analyzed cfDNA before and 6-8 weeks after the start of treatment in 20 advanced HCC patients started LEN. A next-generation sequencer was used for CTNNB1 and TP53. Concerning TERT promoter, -124C&gt;T and -146C&gt;T mutations are researched using digital PCR. In addition, we examined liver tumor biopsy tissues by the same method. CT evaluation was performed at 6-8 weeks and 3-4 months, to assess the efficacy. RESULTS: Frequencies of TERT promoter, CTNNB1 and TP53 mutations in pretreatment cfDNA were 45%, 65% and 65%, but 53%, 41% and 47% in HCC tissues, respectively. There were no clear correlations between these gene mutations and the disease-suppressing effect or progression-free survival. Overall, there were many cases showing a decrease in mutations after LEN treatment. Integrating the reduction of CTNNB1 and TP53 genetic mutations increased the potential for disease suppression. CONCLUSION: This study suggests that analysis of cfDNA in advanced HCC patients may be useful for identifying LEN responders and determining therapeutic efficacy. Furthermore, it has potential for selecting responders for other molecular-targeted drugs.

  7. アセトアミノフェン大量服薬による昏睡型急性肝不全から内科的に救命し得た一例

    佐々木 祥人, 鶴岡 未央, 井上 淳, 二宮 匡史, 佐藤 公亮, 小貫 真純, 澤橋 里子, 大内 啓志, 土井 耕太郎, 渡邊 健吾, 正宗 淳

    日本消化器病学会東北支部例会プログラム・抄録集　217回　99-99　2024/07

    Publisher: 日本消化器病学会-東北支部

  8. 同一薬剤で生じた胆管消失症候群(VBDS)により異なる転帰をたどった2例

    河野 雄一, 佐藤 公亮, 井上 淳, 二宮 匡史, 鶴岡 未央, 小貫 真純, 澤橋 里子, 大内 啓志, 渡邊 健吾, 正宗 淳

    日本消化器病学会東北支部例会プログラム・抄録集　217回　48-48　2024/07

    Publisher: 日本消化器病学会-東北支部

  9. 切除不能肝細胞癌に対するカボザンチニブ7投7休投与法の有用性 東北多施設研究

    黒田 英克, 阿部 珠美, 遠藤 啓, 及川 隆喜, 鶴岡 未央, 二宮 匡史, 藤田 将史, 阿部 和道, 奥本 和夫, 勝見 智大, 佐藤 亘, 五十嵐 剛, 飯野 勢, 遠藤 哲, 田邊 暢一, 沼尾 宏, 木村 修, 伊藤 麻美, 中屋 一碧, 渡辺 拓也, 阿部 弘昭, 藤原 裕大, 遊佐 健二, 佐藤 寛毅, 鈴木 彰子, 吉田 雄一, 柿坂 啓介, 佐原 圭, 宮坂 昭生, 大平 弘正, 上野 義之, 松本 主之

    肝胆膵　88　(5)　648-650　2024/05

    Publisher: (株)アークメディア

    ISSN： 0389-4991

  10. サルコペニア進行における高アンモニア血症と酸化ストレスの関連

    澤橋 里子, 佐野 晃俊, 井上 淳, 二宮 匡史, 鶴岡 未央, 佐藤 公亮, 小貫 真純, 大内 啓志, 正宗 淳

    肝臓　65　(Suppl.1)　A360-A360　2024/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  11. HBVのエンベローブ形成を阻害する低分子化合物の探索

    佐藤 公亮, 井上 淳, 二宮 匡史, 佐野 晃俊, 鶴岡 未央, 小貫 真純, 澤橋 里子, 大内 啓志, 土井 耕太郎, 正宗 淳

    肝臓　65　(Suppl.1)　A363-A363　2024/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  12. 核酸アナログ投与中のB型慢性肝疾患における肝発癌症例の検討 genotype別のHBV DNAレベルの意義

    井上 淳, 小林 智夫, 赤羽 武弘, 高井 智, 木村 修, 南 慎一郎, 阿部 和道, 木田 真美, 芳賀 弘明, 岩田 朋晃, 二宮 匡史, 佐野 晃俊, 鶴岡 未央, 大平 弘正, 上野 義之, 正宗 淳

    肝臓　65　(Suppl.1)　A367-A367　2024/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  13. Atezolizumab+Bevacizumab併用療法を行なった切除不能肝細胞癌症例におけるAtezolizumabに対するAntidrug antibodyの濃度と治療成績についての検討

    大内 啓志, 井上 淳, 二宮 匡史, 佐野 晃俊, 鶴岡 未央, 佐藤 公亮, 小貫 真純, 澤橋 里子, 正宗 淳

    肝臓　65　(Suppl.1)　A374-A374　2024/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  14. 生存予測式を用いた切除不能肝細胞癌Intermediate stageにおける生存延長に寄与する因子の解析

    二宮 匡史, 井上 淳, 鶴岡 未央, 小貫 真純, 澤橋 里子, 大内 啓志, 正宗 淳

    肝臓　65　(Suppl.1)　A378-A378　2024/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  15. アテゾリズマブ・ベバシズマブ併用療法を受けた肝細胞癌患者における予後栄養指数の影響

    藤田 将史, 阿部 和道, 黒田 英克, 及川 隆喜, 阿部 珠美, 二宮 匡史, 鶴岡 未央, 勝見 智大, 佐藤 亘, 飯野 勢, 五十嵐 剛, 田邊 暢一, 沼尾 宏, 木村 修, 松本 主之, 上野 義之, 大平 弘正

    肝臓　65　(Suppl.1)　A492-A492　2024/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  16. 非代償性肝硬変の課題克服を目指して 非代償性肝硬変による難治性腹水患者におけるCARTの有効性・安全性の検討

    鶴岡 未央, 井上 淳, 二宮 匡史, 佐野 晃俊, 佐藤 公亮, 小貫 真純, 澤橋 里子, 大内 啓志, 正宗 淳

    日本消化器病学会雑誌　121　(臨増総会)　A160-A160　2024/03

    Publisher: (一財)日本消化器病学会

    ISSN： 0446-6586

    eISSN： 1349-7693

  17. Lenvatinib投与後における肝細胞癌の病理学的変化とその後の治療効果判定

    二宮 匡史, 鶴岡 未央, 井上 淳, 佐野 晃俊, 佐藤 公亮, 小貫 真純, 澤橋 里子, 大内 啓志, 正宗 淳

    日本消化器病学会雑誌　121　(臨増総会)　A376-A376　2024/03

    Publisher: (一財)日本消化器病学会

    ISSN： 0446-6586

    eISSN： 1349-7693

  18. レジオネラ肺炎の合併により急激な経過で死亡に至った亜急性肝不全の一例

    永井 太郎, 井上 淳, 二宮 匡史, 佐野 晃俊, 鶴岡 未央, 佐藤 公亮, 小貫 真純, 澤橋 里子, 大内 啓志, 正宗 淳

    日本消化器病学会東北支部例会プログラム・抄録集　216回　35-35　2024/02

    Publisher: 日本消化器病学会-東北支部

  19. STRIDE導入後早期にPSL抵抗性irAE腸炎を発症し急性肺炎を併発した肝細胞癌の一例

    渡邊 健吾, 鶴岡 未央, 二宮 匡史, 井上 淳, 佐野 晃俊, 佐藤 公亮, 小貫 真純, 澤橋 里子, 大内 啓志, 正宗 淳

    日本消化器病学会東北支部例会プログラム・抄録集　216回　67-67　2024/02

    Publisher: 日本消化器病学会-東北支部

  20. Usefulness of the Fibrosis-4 index and alanine aminotransferase at 1 year of nucleos(t)ide analog treatment for prediction of hepatocellular carcinoma in chronic hepatitis B patients. International-journal

    Jun Inoue, Takehiro Akahane, Tomoo Kobayashi, Osamu Kimura, Kosuke Sato, Masashi Ninomiya, Tomoaki Iwata, Satoshi Takai, Norihiro Kisara, Toshihiro Sato, Futoshi Nagasaki, Masahito Miura, Takuya Nakamura, Teruyuki Umetsu, Akitoshi Sano, Mio Tsuruoka, Masazumi Onuki, Satoko Sawahashi, Hirofumi Niitsuma, Atsushi Masamune

    Hepatology research : the official journal of the Japan Society of Hepatology　54　(2)　131-141　2024/02

    DOI： 10.1111/hepr.13957 　

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    AIM: Nucleos(t)ide analogs do not completely prevent hepatocellular carcinoma (HCC) in chronic hepatitis B virus infection. This study aimed to evaluate the dynamics of a non-invasive liver fibrosis marker, the Fibrosis-4 (FIB-4) index, for predicting HCC development. METHODS: Among a total of 882 chronically hepatitis B virus infection-infected patients who were treated with nucleos(t)ide analogs, 472 patients without HCC history whose FIB-4 at baseline and 1 year of treatment was obtained were evaluated for the incidence of HCC. RESULTS: The median FIB-4 was 2.00 at baseline and was significantly reduced to 1.58 at 1 year (P < 0.001), but the reduction was small at 2 years or later. When a receiver operating characteristic analysis of FIB-4 was performed to predict HCC within 5 years, the area under the curve of FIB-4 at 1 year was higher than that at baseline (0.676 vs. 0.599). The HCC incidence was significantly higher in patients with FIB-4 ≥1.58 than in those with FIB-4 <1.58 (14.8% vs. 3.6% at 10 years, P < 0.001). Additionally, an abnormal alanine aminotransferase (≥31 U/L) at 1 year was an independent risk for HCC. When a fibrosis and alanine aminotransferase-1 (FAL-1) score was evaluated as an applicable number of FIB-4 ≥1.58, and alanine aminotransferase ≥31 as 0, 1, and 2, the HCC risk in patients with score 2 was significantly higher than in those with score 1 or score 0 (24.1% vs. 9.8% vs. 0.7% at 10 years, P < 0.001). CONCLUSIONS: FIB-4 ≥1.58 and alanine aminotransferase ≥31 at 1 year of nucleos(t)ide analog was an independent risk factor for HCC development, and a score using these factors stratified the risk of HCC.

  21. 【チーム医療で取り組む肝胆膵疾患の栄養マネジメント】肝硬変患者のサルコペニア進行予防を目指した栄養マネジメント アミノ酸代謝の視点を交えて

    佐野 晃俊, 嘉数 英二, 井上 淳, 二宮 匡史, 鶴岡 未央, 佐藤 公亮, 小貫 真純, 澤橋 里子, 大内 啓志, 正宗 淳

    肝胆膵　88　(1)　71-78　2024/01

    Publisher: (株)アークメディア

    ISSN： 0389-4991

  22. Type 2 Diabetes Mellitus is a Risk Factor for Skeletal Muscle Loss in the Course of Dietary Treatment for Patients with Metabolic Dysfunction-associated Steatotic Liver Disease

    Akitoshi Sano, Manami Sasaki, Jun Inoue, Eiji Kakazu, Masashi Ninomiya, Mio Tsuruoka, Kosuke Sato, Masazumi Onuki, Satoko Sawahashi, Keishi Ouchi, Kotaro Doi, Yukio Katori, Atsushi Masamune

    Internal Medicine　2024

    Publisher: Japanese Society of Internal Medicine

    DOI： 10.2169/internalmedicine.3787-24 　

    ISSN： 0918-2918

    eISSN： 1349-7235

  23. 【チーム医療で取り組む肝胆膵疾患の栄養マネジメント】肝硬変患者のサルコペニア進行予防を目指した栄養マネジメント アミノ酸代謝の視点を交えて

    佐野 晃俊, 嘉数 英二, 井上 淳, 二宮 匡史, 鶴岡 未央, 佐藤 公亮, 小貫 真純, 澤橋 里子, 大内 啓志, 正宗 淳

    肝胆膵　88　(1)　71-78　2024/01

    Publisher: (株)アークメディア

    ISSN： 0389-4991

  24. A new model to estimate duration of survival in patients with hepatocellular carcinoma with BCLC intermediate stage. International-journal

    Masashi Ninomiya, Mio Tsuruoka, Jun Inoue, Atsushi Hiraoka, Tomoaki Iwata, Akitoshi Sano, Kosuke Sato, Masazumi Onuki, Satoko Sawahashi, Hidekatsu Kuroda, Takayoshi Oikawa, Masashi Fujita, Kazumichi Abe, Tomohiro Katsumi, Wataru Sato, Go Igarashi, Chikara Iino, Tetsu Endo, Nobukazu Tanabe, Hiroshi Numao, Katsunori Iijima, Takayuki Matsumoto, Hiromasa Ohira, Yoshiyuki Ueno, Atsushi Masamune

    Scientific reports　13　(1)　20739-20739　2023/11/25

    DOI： 10.1038/s41598-023-48068-7 　

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    It is difficult to determine whether an individual therapy contributes to the elongation of survival because of the difficulty of organizing clinical research in patients who receive multiple treatments in HCC. We aimed to establish a new model of survival prediction in patients with intermediate stage HCC to establish standards in the recent and coming multi-MTA era. This analysis was prepared using a data set of 753 patients diagnosed HCC prior to 2017. Multiple regression analysis showed age, naïve or recurrence, the size of the largest tumor nodule, the number of nodules, total bilirubin, albumin and α-fetoprotein as independent predictors of survival. A Weibull model had the best fit and, based on these predictors, we established a new predicted survival model. The survival duration can be predicted the proposed model; EXP (4.02580 + (- 0.0086253) × age + (- 0.34667) × (naïve/recurrence) + (- 0.034962) × (number of nodules) + (- 0.079447) × (the size of the largest nodule) + (- 0.21696) × (total bilirubin) + 0.27912 × (albumin) + (- 0.00014741) × (α-fetoprotein)) × (- natural logarithm(0.5))^0.67250. This model is useful for the planning and evaluating the efficacy of recent sequential therapies in multi-MTA era.

  25. 切除不能肝細胞癌におけるSecond line以降のアテゾリズマブ+ベバシズマブ療法導入症例の治療成績

    二宮 匡史, 鶴岡 未央, 井上 淳, 佐野 晃俊, 佐藤 公亮, 小貫 正純, 澤橋 里子, 黒田 英克, 及川 隆喜, 勝見 智大, 阿部 和道, 藤田 将史, 佐藤 亘, 五十嵐 剛, 飯野 勢, 田邊 暢一, 沼尾 宏, 木村 修, 上野 義之, 正宗 淳

    日本消化器病学会雑誌　120　(臨増大会)　A813-A813　2023/10

    Publisher: (一財)日本消化器病学会

    ISSN： 0446-6586

    eISSN： 1349-7693

  26. 切除不能肝細胞癌におけるSecond line以降のアテゾリズマブ+ベバシズマブ療法導入症例の治療成績

    二宮 匡史, 鶴岡 未央, 井上 淳, 佐野 晃俊, 佐藤 公亮, 小貫 正純, 澤橋 里子, 黒田 英克, 及川 隆喜, 勝見 智大, 阿部 和道, 藤田 将史, 佐藤 亘, 五十嵐 剛, 飯野 勢, 田邊 暢一, 沼尾 宏, 木村 修, 上野 義之, 正宗 淳

    日本消化器病学会雑誌　120　(臨増大会)　A813-A813　2023/10

    Publisher: (一財)日本消化器病学会

    ISSN： 0446-6586

    eISSN： 1349-7693

  27. 医療現場におけるダイバーシティを目指して 消化器内科における女性医師とメディカルスタッフのアンケート結果から

    鶴岡 未央, 井上 淳, 二宮 匡史, 岩田 朋晃, 佐野 晃俊, 佐藤 公亮, 小貫 真純, 澤橋 里子, 正宗 淳

    日本消化器病学会雑誌　120　(9)　746-754　2023/09

    Publisher: (一財)日本消化器病学会

    ISSN： 0446-6586

    eISSN： 1349-7693

  28. 消化器癌に対する免疫療法の現状と課題 当院のDurvalumab及び抗CTLA-4抗体使用時のIMH患者の現状と当科でのタクロリムスの使用経験

    鶴岡 未央, 二宮 匡史, 正宗 淳

    肝臓　64　(Suppl.2)　A559-A559　2023/09

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  29. Effectiveness of tacrolimus in a case of immune checkpoint inhibitor-induced hepatotoxicity that was refractory to steroids and mycophenolate mofetil.

    Kosuke Sato, Jun Inoue, Masashi Ninomiya, Tomoaki Iwata, Akitoshi Sano, Mio Tsuruoka, Masazumi Onuki, Satoko Sawahashi, Keishi Ouchi, Atsushi Masamune

    Clinical journal of gastroenterology　2023/07/22

    DOI： 10.1007/s12328-023-01832-8 　

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    Immune checkpoint inhibitors (ICIs) sometimes induce immune-mediated hepatotoxicity (IMH), and corticosteroids and mycophenolate mofetil (MMF) are recommended for the treatment of IMH. However, there is no consensus on the treatment of IMH refractory to these drugs. Here, we report a case of refractory IMH that was successfully treated with tacrolimus. A 69-year-old man presented with liver injury after receiving durvalumab, an ICI, for lung cancer. He was diagnosed with IMH and received corticosteroids including methylprednisolone pulses and MMF, but his liver damage did not improve. Liver histology showed infiltration of inflammatory cells, mainly CD8 + T cells, in the portal area. Tacrolimus was added to corticosteroid and MMF to suppress mainly T cells. After the tacrolimus administration, the liver damage promptly improved. Since IMH is thought to be caused by activated CD8 + T-cell infiltration, T-cell suppression may be an effective treatment. This case suggests that tacrolimus may be an effective option for IMH refractory to corticosteroids or MMF if CD8 + T-cell infiltration is confirmed in the liver tissue.

  30. 肝胆膵がん治療の現状と未来 当院における薬物療法と組み合わせた集学的治療による進行肝細胞癌CR症例の検討

    鶴岡 未央, 二宮 匡史, 井上 淳, 佐野 晃俊, 正宗 淳

    日本消化器病学会東北支部例会・日本消化器内視鏡学会東北支部例会プログラム・抄録集　215回・170回　85-85　2023/07

    Publisher: 日本消化器病学会-東北支部

  31. 肝硬変の成因と病態の推移 当院の肝癌治療患者における肝硬変の成因推移

    佐野 晃俊, 井上 淳, 嘉数 英二, 二宮 匡史, 岩田 朋晃, 鶴岡 未央, 佐藤 公亮, 小貫 真純, 澤橋 里子, 大内 啓志, 正宗 淳

    肝臓　64　(Suppl.1)　A245-A245　2023/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  32. MAFLD患者における減量指導と筋量減少の関係

    佐野 晃俊, 井上 淳, 嘉数 英二, 二宮 匡史, 岩田 朋晃, 鶴岡 未央, 佐藤 公亮, 小貫 真純, 澤橋 里子, 大内 啓志, 正宗 淳

    肝臓　64　(Suppl.1)　A362-A362　2023/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  33. B型肝炎の核酸アナログ投与例における代謝関連因子と肝発癌・線維化の関連について

    井上 淳, 赤羽 武弘, 小林 智夫, 木村 修, 高井 智, 木皿 典宏, 佐藤 俊裕, 長崎 太, 三浦 雅人, 梅津 輝行, 二宮 匡史, 岩田 朋晃, 佐野 晃俊, 鶴岡 未央, 佐藤 公亮, 小貫 真純, 澤橋 里子, 新妻 宏文, 正宗 淳

    肝臓　64　(Suppl.1)　A423-A423　2023/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  34. 肝疾患における有害事象をめぐる諸問題(薬物性肝障害を含めて) 当院のirAE肝障害患者の現状とステロイド及びMMF抵抗性症例に対するタクロリムスの使用経験

    鶴岡 未央, 二宮 匡史, 正宗 淳

    肝臓　64　(Suppl.1)　A214-A214　2023/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  35. 肝細胞癌BCLC C期における生存期間延長に寄与する因子の解析

    二宮 匡史, 井上 淳, 佐野 晃俊, 鶴岡 未央, 佐藤 公亮, 小貫 真純, 澤橋 里子, 正宗 淳

    肝臓　64　(Suppl.1)　A374-A374　2023/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  36. HBVのエンベロープ形成を阻害する化合物の探索

    佐藤 公亮, 井上 淳, 二宮 匡史, 岩田 朋晃, 佐野 晃俊, 鶴岡 未央, 小貫 真純, 澤橋 里子, 大内 啓志, 正宗 淳

    肝臓　64　(Suppl.1)　A415-A415　2023/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  37. 門脈大循環短絡を有する肝性脳症に対する血管内治療の効果の検討

    小貫 真純, 井上 淳, 二宮 匡史, 岩田 朋晃, 佐野 晃俊, 鶴岡 未央, 佐藤 公亮, 澤橋 里子, 大内 啓志, 正宗 淳

    肝臓　64　(Suppl.1)　A463-A463　2023/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  38. 肝疾患における有害事象をめぐる諸問題(薬物性肝障害を含めて) 当院のirAE肝障害患者の現状とステロイド及びMMF抵抗性症例に対するタクロリムスの使用経験

    鶴岡 未央, 二宮 匡史, 正宗 淳

    肝臓　64　(Suppl.1)　A214-A214　2023/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  39. 肝硬変の成因と病態の推移 当院の肝癌治療患者における肝硬変の成因推移

    佐野 晃俊, 井上 淳, 嘉数 英二, 二宮 匡史, 岩田 朋晃, 鶴岡 未央, 佐藤 公亮, 小貫 真純, 澤橋 里子, 大内 啓志, 正宗 淳

    肝臓　64　(Suppl.1)　A245-A245　2023/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  40. MAFLD患者における減量指導と筋量減少の関係

    佐野 晃俊, 井上 淳, 嘉数 英二, 二宮 匡史, 岩田 朋晃, 鶴岡 未央, 佐藤 公亮, 小貫 真純, 澤橋 里子, 大内 啓志, 正宗 淳

    肝臓　64　(Suppl.1)　A362-A362　2023/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  41. 肝細胞癌BCLC C期における生存期間延長に寄与する因子の解析

    二宮 匡史, 井上 淳, 佐野 晃俊, 鶴岡 未央, 佐藤 公亮, 小貫 真純, 澤橋 里子, 正宗 淳

    肝臓　64　(Suppl.1)　A374-A374　2023/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  42. HBVのエンベロープ形成を阻害する化合物の探索

    佐藤 公亮, 井上 淳, 二宮 匡史, 岩田 朋晃, 佐野 晃俊, 鶴岡 未央, 小貫 真純, 澤橋 里子, 大内 啓志, 正宗 淳

    肝臓　64　(Suppl.1)　A415-A415　2023/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  43. B型肝炎の核酸アナログ投与例における代謝関連因子と肝発癌・線維化の関連について

    井上 淳, 赤羽 武弘, 小林 智夫, 木村 修, 高井 智, 木皿 典宏, 佐藤 俊裕, 長崎 太, 三浦 雅人, 梅津 輝行, 二宮 匡史, 岩田 朋晃, 佐野 晃俊, 鶴岡 未央, 佐藤 公亮, 小貫 真純, 澤橋 里子, 新妻 宏文, 正宗 淳

    肝臓　64　(Suppl.1)　A423-A423　2023/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  44. 門脈大循環短絡を有する肝性脳症に対する血管内治療の効果の検討

    小貫 真純, 井上 淳, 二宮 匡史, 岩田 朋晃, 佐野 晃俊, 鶴岡 未央, 佐藤 公亮, 澤橋 里子, 大内 啓志, 正宗 淳

    肝臓　64　(Suppl.1)　A463-A463　2023/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  45. Entecavir投与中にHBV DNAが検出されたB型慢性肝炎患者におけるTenofovir alafenamide fumarateへの切り替えの検討

    佐藤 公亮, 井上 淳, 二宮 匡史, 岩田 朋晃, 鶴岡 未央, 小貫 真純, 澤橋 里子, 大内 啓志, 正宗 淳

    日本消化器病学会雑誌　120　(臨増総会)　A420-A420　2023/03

    Publisher: (一財)日本消化器病学会

    ISSN： 0446-6586

    eISSN： 1349-7693

  46. 女性医師として仕事を続けるコツ～多様性のある働き方～ 医療現場におけるダイバーシティを目指して

    鶴岡 未央, 井上 淳, 二宮 匡史, 正宗 淳

    日本消化器病学会東北支部例会プログラム・抄録集　214回　68-68　2023/02

    Publisher: 日本消化器病学会-東北支部

  47. irAE肝障害の難治例に対してタクロリムスが奏功した1例

    佐藤 公亮, 井上 淳, 二宮 匡史, 岩田 朋晃, 佐野 晃俊, 鶴岡 未央, 小貫 真純, 澤橋 里子, 正宗 淳

    日本消化器病学会東北支部例会プログラム・抄録集　214回　95-95　2023/02

    Publisher: 日本消化器病学会-東北支部

  48. [Achieving diversity in the medical field:a survey of female physicians and medical staff in the Department of Gastroenterology].

    Mio Tsuruoka, Jun Inoue, Masashi Ninomiya, Tomoaki Iwata, Akitoshi Sano, Kosuke Sato, Masazumi Onuki, Satoko Sawahashi, Atsushi Masamune

    Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology　120　(9)　746-754　2023

    DOI： 10.11405/nisshoshi.120.746 　

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    From the perspective of diversity in the medical field, the relationship between physicians and medical staff is one of the important factors. In this study, a survey was conducted on female doctors for 136 medical staff who are deeply involved in gastroenterology. Furthermore, another survey was conducted on 10 female doctors in gastroenterology regarding their relationship with the medical staff and their work-life balance. Consequently, 89% of the medical staff had experienced a situation where they relied on female doctors. Seventy-eight percent felt a necessity for female doctors, and it was observed that the demand for female doctors in gastroenterology would remain high in the future. Conversely, regarding the necessity of female doctors, 22% responded "neither agree nor disagree," and several of them believed that the personal qualities of a doctor were the most significant versus being a female. Moreover, it was noted that the idea of genderless thinking is becoming prevalent in the medical field. In addition, half of the female doctors considered gastroenterology to be a workplace that is easy for female doctors. The most common reason was that it broadens the options for working styles because skills, including gastrointestinal endoscopy and ultrasonography, can be acquired. Ninety percent of female doctors had no experience of trouble with medical staff due to being female. Conversely, 80% responded that they could work smoothly with staff in their interactions with female patients. Since medical treatment is based on gender differences, it is difficult not to be aware of them. Creating an environment wherein female doctors are freed from gender stereotypes and can utilize being female as one of their abilities while responding to the needs of patients and the medical field will be necessary.

  49. Switching to Tenofovir Alafenamide Fumarate in Chronic Hepatitis B Patients Who Had Detectable HBV DNA during Treatment with Entecavir.

    Kosuke Sato, Jun Inoue, Takehiro Akahane, Tomoo Kobayashi, Satoshi Takai, Takuya Nakamura, Toshihiro Sato, Osamu Kimura, Masashi Ninomiya, Tomoaki Iwata, Akitoshi Sano, Mio Tsuruoka, Masazumi Onuki, Satoko Sawahashi, Hirofumi Niitsuma, Atsushi Masamune

    The Tohoku journal of experimental medicine　258　(4)　277-285　2022/11/12

    DOI： 10.1620/tjem.2022.J084 　

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    Nucleos(t)ide analogues (NAs) suppress hepatitis B virus (HBV) replication, but the risk of hepatocellular carcinoma still remains. The presence of detectable HBV DNA in the serum during NA therapies for chronic hepatitis B patients has been reported to be associated with the risk of hepatocellular carcinoma. In this study, we investigated the antiviral effect of switching from entecavir (ETV) to tenofovir alafenamide fumarate (TAF) in chronic hepatitis B patients who had detectable HBV DNA in the serum at least once within a year. Among a total of 77 cases in 7 hospitals that switched NAs from ETV to TAF, 23 patients with detectable HBV DNA in a year before switching were analyzed. When the detection frequencies of HBV DNA in the 1st and 2nd years after switching to TAF were analyzed, they were significantly lower than those in the year before switching (68.8% vs. 34.1% for the 1st year and 21.3% for the 2nd year, P < 0.001 for both). The HBsAg decline tended to be larger after switching than before (-2.5% vs. -3.0% for 1st year and -3.1% for 2nd year), but the difference was not significant. One patient died of a cardiovascular event 11 months after the treatment switch, but no adverse effects due to TAF including renal function were observed. In conclusion, it was suggested that switching from ETV to TAF might be effective to suppress the HBV DNA level further in patients whose HBV DNA is detectable, even if at a very low level.

  50. A Case of Duodenal Variceal Rupture during Atezolizumab and Bevacizumab Treatment for Hepatocellular Carcinoma.

    Mio Tsuruoka, Jun Inoue, Keishi Ouchi, Kaname Uno, Hideaki Itami, Masashi Ninomiya, Tomoaki Iwata, Akitoshi Sano, Kosuke Sato, Masazumi Onuki, Satoko Sawahashi, Tomoyuki Koike, Atsushi Masamune

    Internal medicine (Tokyo, Japan)　62　(10)　1467-1472　2022/10/05

    DOI： 10.2169/internalmedicine.0629-22 　

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    Duodenal varices are detected infrequently, and their rupture is very rare. We encountered an 87-year-old man who developed duodenal varices rupture during chemotherapy with atezolizumab and bevacizumab (ATZ/BV) for hepatocellular carcinoma. We identified massive bleeding of a ruptured varix in the horizontal portion of the duodenum with emergency esophagogastroduodenoscopy (EGD). Successful hemostasis was achieved by endoscopic injection sclerotherapy with Histoacryl. Although ATZ/BV can cause esophageal varices rupture, there have been no cases of duodenal varices rupture. We should take care to check the duodenal varices as well as esophagogastric varices before ATZ/BV treatment.

  51. NAFLD/NASHに対する選択的PPARαモジュレータおよび各種糖尿病薬等の効果の検討

    澤橋 里子, 佐野 晃俊, 井上 淳, 二宮 匡史, 岩田 朋晃, 鶴岡 未央, 佐藤 公亮, 小貫 真純, 大内 啓志, 正宗 淳

    肝臓　63　(Suppl.3)　A799-A799　2022/10

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  52. Atezolizumab+Bevacizumab投与後に急速に進行したHCCに対し肝動注化学療法が著効した一例

    鶴岡 未央, 井上 淳, 二宮 匡史, 岩田 朋晃, 佐野 晃俊, 佐藤 公亮, 小貫 真純, 澤橋 里子, 正宗 淳

    肝臓　63　(Suppl.3)　A819-A819　2022/10

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  53. Switching to tenofovir alafenamide versus continued therapy in chronic hepatitis B patients who were treated with entecavir: A prospective, multicenter, randomized controlled study. International-journal

    Kosuke Sato, Jun Inoue, Takehiro Akahane, Tomoo Kobayashi, Shuichi Sato, Norihiro Kisara, Masashi Ninomiya, Tomoaki Iwata, Akitoshi Sano, Mio Tsuruoka, Masazumi Onuki, Atsushi Masamune

    Medicine　101　(39)　e30630　2022/09/30

    DOI： 10.1097/MD.0000000000030630 　

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    BACKGROUNDS: Entecavir (ETV) and tenofovir alafenamide fumarate (TAF) have been used widely to treat patients with chronic hepatitis B virus (HBV) infection, but it is still unclear how best to use these drugs. Although some studies compared the efficacies of treatment switch from ETV to TAF, there has been no randomized study. METHODS: We performed a prospective multicenter randomized controlled study in which subjects were enrolled from April 2018 to June 2019 and observed for 2 years until March 2021 to clarify the efficacy and safety of switching from ETV to TAF. RESULTS: Thirty-three patients were enrolled and randomized into 2 groups, and a total of 30 patients were evaluated; a TAF-switching group (n = 16) and an ETV-continuing group (n = 14). The mean age of the 30 patients was 61 years old and 18 patients (60%) were male. The serum HBV DNA in all patients were below detection limit. The mean change in hepatitis B surface antigen (HBsAg) levels after 2 years was not significantly different between the TAF and ETV groups (-0.08 vs -0.20 log IU/mL, P = .07). Comparing the group with a HBsAg decline (≤ -0.1 log IU/mL) and a group without a HBsAg decline in an overall analysis, the prior ETV duration was significantly shorter in the HBsAg-declined group (49 vs 92 months, P = .03). Although the eGFR levels tended to decrease in the TAF group compared to ETV (-6.15 vs -2.26 mL/min/1.73 m2, P = .09), no significant differences were observed in patients with baseline eGFR < 60 (-2.49 vs 0.40 mL/min/1.73 m2, P = .25). CONCLUSION: The efficacy and safety were comparable in the TAF-switching group and the ETV-continuing group. Because the present study was conducted in limited patients, a larger study will be required.

  54. C型肝炎制御下での諸問題と治療戦略 DAA治療後に肝線維化が改善する症例に特徴的なmiRNA発現パターンの同定

    近藤 泰輝, 小暮 高之, 二宮 匡史

    肝臓　63　(Suppl.2)　A525-A525　2022/09

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  55. 実臨床における進行肝癌sequential療法下でのアテゾリズマブ+ベバシズマブ療法導入症例の治療成績

    二宮 匡史, 井上 淳, 岩田 朋晃, 佐野 晃俊, 嶋岡 未央, 佐藤 公亮, 小貫 真純, 正宗 淳

    肝臓　63　(Suppl.2)　A602-A602　2022/09

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  56. Evaluation of a Capillary Microsampling Device for Analyzing Plasma Lenvatinib Concentration in Patients with Hepatocellular Carcinoma

    Akihiro Saito, Masafumi Kikuchi, Yuko Matsumoto, Erina Sugawara, Gesshu Takao, Hayato Inomata, Akane Takahashi, Yuji Sato, Masaki Kumondai, Yu Sato, Toshihiro Sato, Masashi Ninomiya, Jun Inoue, Masamitsu Maekawa, Nariyasu Mano

    Therapeutic Drug Monitoring　Publish Ahead of Print　2022/07/21

    Publisher: Ovid Technologies (Wolters Kluwer Health)

    DOI： 10.1097/ftd.0000000000001013 　

    ISSN： 0163-4356

  57. Non-Achievement of Alanine Aminotransferase Normalization Associated with the Risk of Hepatocellular Carcinoma during Nucleos(t)ide Analogue Therapies: A Multicenter Retrospective Study. International-journal

    Jun Inoue, Tomoo Kobayashi, Takehiro Akahane, Osamu Kimura, Kosuke Sato, Masashi Ninomiya, Tomoaki Iwata, Satoshi Takai, Norihiro Kisara, Toshihiro Sato, Futoshi Nagasaki, Masahito Miura, Takuya Nakamura, Teruyuki Umetsu, Akitoshi Sano, Mio Tsuruoka, Masazumi Onuki, Hirofumi Niitsuma, Atsushi Masamune, Therme Study Group

    Journal of clinical medicine　11　(9)　2022/04/22

    DOI： 10.3390/jcm11092354 　

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    Patients with a chronic hepatitis B virus (HBV) infection who are treated with nucleos(t)ide analogues (NAs) are still at risk for hepatocellular carcinoma (HCC), and it has been clinically questioned whether patients with a high risk of HCC can be identified efficiently. We aimed to clarify the risk factors associated with the development of HCC during NA therapies. A total of 611 chronically HBV-infected patients without a history of HCC, who were treated with NAs for more than 6 months (median 72 months), from 2000 to 2021, were included from 16 hospitals in the Tohoku district in Japan. Incidences of HCC occurrence were analyzed with clinical factors, including on-treatment responses. Alanine aminotransferase (ALT) normalization, based on the criteria of three guidelines, was analyzed with other parameters, including the age−male−ALBI−platelets (aMAP) risk score. During the observation period, 48 patients developed HCC, and the cumulative HCC incidence was 10.6% at 10 years. Non-achievement of ALT normalization at 1 year of therapy was mostly associated with HCC development when ALT ≤ 30 U/L was used as the cut-off (cumulative incidence, 19.9% vs. 5.3% at 10 years, p < 0.001). The effectiveness of the aMAP risk score at the start of treatment was validated in this cohort. A combination of an aMAP risk score ≥ 50 and non-achievement of ALT normalization could stratify the risk of HCC significantly, and notably, there was no HCC development in 103 patients without these 2 factors. In conclusion, non-achievement of ALT normalization (≤30 U/L) at 1 year might be useful in predicting HCC during NA therapies and, in combination with the aMAP risk score, could stratify the risk more precisely.

  58. 門脈血中L-メチオニン・L-チロシンの低下はフマル酸代謝・Nrf2を介した成熟VLDL合成を抑制し肝細胞脂肪変性を惹起する

    佐野 晃俊, 嘉数 英二, 井上 淳, 二宮 匡史, 岩田 朋晃, 鶴岡 未央, 佐藤 公亮, 小貫 真純, 正宗 淳

    日本消化器病学会雑誌　118　(臨増大会)　A730-A730　2021/10

    Publisher: (一財)日本消化器病学会

    ISSN： 0446-6586

    eISSN： 1349-7693

  59. レンバチニブ中止後の治療と予後についての検討

    奥本 和夫, 及川 隆喜, 二宮 匡史, 遠藤 哲, 勝見 智大, 上野 義之

    肝臓　62　(Suppl.2)　A554-A554　2021/09

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  60. 糖尿病併非アルコール性脂肪性肝炎に対するピオグリタゾンとルセオグリフロジンの治療効果比較試験(後ろ向きコホート研究)

    小貫 真純, 嘉数 英二, 佐野 晃俊, 井上 淳, 二宮 匡史, 岩田 朋晃, 鶴岡 未央, 佐藤 公亮, 正宗 淳

    肝臓　62　(Suppl.2)　A571-A571　2021/09

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  61. レンバチニブ中止後の治療と予後についての検討

    奥本 和夫, 及川 隆喜, 二宮 匡史, 遠藤 哲, 勝見 智大, 上野 義之

    肝臓　62　(Suppl.2)　A554-A554　2021/09

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  62. 骨格筋量の推移からみたレンバチニブ治療と生命予後の検討 東北地方多施設共同検討

    藤田 将史, 阿部 和道, 大平 弘正, 及川 隆喜, 二宮 匡史, 奥本 和夫, 佐藤 亘, 遠藤 哲, 田邉 暢一, 滝川 康裕, 上野 義之

    肝臓　62　(Suppl.2)　A555-A555　2021/09

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  63. Reactivation of hepatitis C virus with severe hepatitis flare during steroid administration for interstitial pneumonia.

    Kosuke Sato, Jun Inoue, Eiji Kakazu, Masashi Ninomiya, Tomoaki Iwata, Akitoshi Sano, Mio Tsuruoka, Atsushi Masamune

    Clinical journal of gastroenterology　14　(4)　1221-1226　2021/08

    DOI： 10.1007/s12328-021-01432-4 　

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    Hepatitis C virus reactivation (HCVr) was defined previously as an increase in HCV RNA level of ≥ 1 log10 IU/mL from baseline HCV RNA level after chemotherapies or immunosuppressive therapies, but HCVr during a steroid monotherapy has rarely been reported. Here we report a 75-year-old Japanese female with chronic hepatitis C (genotype 2a) who developed HCVr after the administration of prednisolone for interstitial pneumonia. She experienced alanine aminotransferase (ALT) flare with icterus, but after the tapering of prednisolone and a liver supporting therapy, levels of HCV RNA and ALT were gradually decreased. Then, she received an anti-viral therapy with sofosbuvir/ledipasvir. Although HCV relapsed 4 weeks after the therapy, a second therapy with glecaprevir/pibrentasvir was successful. This case suggests that HCVr with hepatitis flare can occur even after a steroid monotherapy, and we should pay attention to HCVr when we administer prednisolone for patients with HCV chronic infection.

  64. The Exosome-Associated Tetraspanin CD63 Contributes to the Efficient Assembly and Infectivity of the Hepatitis B Virus. International-journal

    Masashi Ninomiya, Jun Inoue, Eugene W Krueger, Jing Chen, Hong Cao, Atsushi Masamune, Mark A McNiven

    Hepatology communications　5　(7)　1238-1251　2021/07

    DOI： 10.1002/hep4.1709 　

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    Currently, the hepatocellular trafficking pathways that are used by the hepatitis B virus (HBV) during viral infection and shedding are poorly defined. It is known that the HBV uses late endosomal and multivesicular body (MVB) compartments for assembly and release. The intraluminal vesicles (ILVs) generated within MVBs have also been implicated in the late synthesis stages of a variety of pathogenic viruses. We recently observed that the HBV within infected hepatocytes appears to associate with the tetraspanin protein CD63, known to be a prominent and essential component of ILVs. Immunofluorescence microscopy of HBV-expressing cells showed that CD63 colocalized with HBV proteins (large hepatitis B surface antigens [LHBs] and hepatitis B core) and labeled an exceptionally large number of secreted extracellular vesicles of uniform size. Small interfering RNA (siRNA)-mediated depletion of CD63 induced a substantial accumulation of intracellular LHBs protein but did not alter the levels of either intracellular or extracellular HBV DNA, nor pregenomic RNA. Consistent with these findings, we found that markedly less LHBs protein was associated with the released HBV particles from CD63 siRNA-treated cells. Importantly, the HBV viral particles that were shed from CD63-depleted cells were substantially less infective than those collected from control cells with normal CD63 levels. Conclusion: These findings implicate the tetraspanin protein CD63 as a marker and an important component in the formation and release of infectious HBV particles.

  65. Envelope Proteins of Hepatitis B Virus: Molecular Biology and Involvement in Carcinogenesis. International-journal

    Jun Inoue, Kosuke Sato, Masashi Ninomiya, Atsushi Masamune

    Viruses　13　(6)　2021/06/11

    DOI： 10.3390/v13061124 　

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    The envelope of hepatitis B virus (HBV), which is required for the entry to hepatocytes, consists of a lipid bilayer derived from hepatocyte and HBV envelope proteins, large/middle/small hepatitis B surface antigen (L/M/SHBs). The mechanisms and host factors for the envelope formation in the hepatocytes are being revealed. HBV-infected hepatocytes release a large amount of subviral particles (SVPs) containing L/M/SHBs that facilitate escape from the immune system. Recently, novel drugs inhibiting the functions of the viral envelope and those inhibiting the release of SVPs have been reported. LHBs that accumulate in ER is considered to promote carcinogenesis and, especially, deletion mutants in the preS1/S2 domain have been reported to be associated with the development of hepatocellular carcinoma (HCC). In this review, we summarize recent reports on the findings regarding the biological characteristics of HBV envelope proteins, their involvement in HCC development and new agents targeting the envelope.

  66. 現在及びこれからの肝炎ウイルス研究のlandscape B型肝炎ウイルス感染による小胞輸送の変化がウイルス放出に与える影響

    井上 淳, 二宮 匡史, 正宗 淳

    肝臓　62　(Suppl.1)　A127-A127　2021/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  67. 当院の肝疾患相談室における活動の実態と今後の課題

    井上 淳, 嘉数 英二, 二宮 匡史, 岩田 朋晃, 佐野 晃俊, 鶴岡 未央, 佐藤 公亮, 正宗 淳

    肝臓　62　(Suppl.1)　A240-A240　2021/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  68. 肝細胞癌BCLC B期の治療の変化分子標的薬は治療成績に貢献したのか

    二宮 匡史, 井上 淳, 正宗 淳

    肝臓　62　(Suppl.1)　A292-A292　2021/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  69. 当院における核酸アナログ製剤投与中のB型慢性肝炎患者の尿細管障害に関する検討

    佐藤 公亮, 井上 淳, 鶴岡 未央, 佐野 晃俊, 岩田 朋晃, 二宮 匡史, 嘉数 英二, 正宗 淳

    肝臓　62　(Suppl.1)　A345-A345　2021/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  70. 分子標的薬適応となった肝細胞癌患者のcell free DNAと肝腫瘍組織の遺伝子変異解析

    鶴岡 未央, 二宮 匡史, 正宗 淳, 井上 淳, 嘉数 英二, 岩田 朋晃, 佐野 晃俊, 佐藤 公亮

    肝臓　62　(Suppl.1)　A366-A366　2021/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  71. Plasma free amino acids are associated with sarcopenia in the course of hepatocellular carcinoma recurrence. International-journal

    Akitoshi Sano, Shunichi Tsuge, Eiji Kakazu, Tomoaki Iwata, Masashi Ninomiya, Mio Tsuruoka, Jun Inoue, Atsushi Masamune

    Nutrition (Burbank, Los Angeles County, Calif.)　84　111007-111007　2021/04

    DOI： 10.1016/j.nut.2020.111007 　

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    OBJECTIVE: Sarcopenia worsens the prognosis of patients with hepatocellular carcinoma (HCC). The aim of this study was to elucidate the plasma free amino acids (PFAAs) associated with sarcopenia or myosteatosis in the course of HCC recurrence. METHODS: In this cross-sectional study, 187 patients were enrolled retrospectively. All patients experienced more than one hospitalization (mean times, 2.65) owing to HCC recurrence. The skeletal muscle index (SMI) and muscle attenuation (MA) were measured by a transverse computed tomography (CT) scan image at the third lumbar vertebra (L3). The changes in the concentration of 24 PFAAs, SMI, and MA in the same patient between recurrences were defined as Δ. The associations between sarcopenia, myosteatosis, and PFAAs were evaluated by a logistic regression model. The ΔSMI and ΔMA were compared between the patients who received branched-chain amino acids (BCAAs) formulation and those who did not. RESULTS: Patients with sarcopenia showed lower survival rate; the 1-, 3-, and 5-y survival rates were 85%, 42%, and 9%, respectively. Multivariate analysis revealed that the level of total BCAAs was significantly associated with sarcopenia. The correlation coefficient value between the change of leucine (ΔLeu) and ΔSMI was highest (R = 0.256; P < 0.001) among the PFAAs. In the Child-Pugh grade B or C, the decrease of SMI was significantly more suppressed in the patients with the BCAAs formulation than in those without BCAAs formulation (ΔSMI: mean change -0.98 versus -3.45 cm²/m²; P = 0.038). CONCLUSION: Among the PFAAs, the level of BCAAs was associated with sarcopenia in the course of HCC recurrence.

  72. Steatotic hepatocytes release mature VLDL via methionine and tyrosine metabolism in a Keap1‐Nrf2 dependent manner

    Akitoshi Sano, Eiji Kakazu, Shin Hamada, Jun Inoue, Masashi Ninomiya, Tomoaki Iwata, Mio Tsuruoka, Kosuke Sato, Atsushi Masamune

    Hepatology　2021/03/16

    Publisher: Wiley

    DOI： 10.1002/hep.31808 　

    ISSN： 0270-9139

    eISSN： 1527-3350

  73. 肝癌における薬物療法の診療体系 肝細胞癌BCLC C期の治療の変化Lenvatinibは治療成績に貢献したのか

    二宮 匡史, 井上 淳, 正宗 淳

    日本消化器病学会雑誌　118　(臨増総会)　A112-A112　2021/03

    Publisher: (一財)日本消化器病学会

    ISSN： 0446-6586

    eISSN： 1349-7693

  74. 糖尿病合併非アルコール性脂肪性肝炎に対するピオグリタゾンとルセオグリフロジンの治療効果比較試験 後ろ向きコホート研究

    小貫 真純, 佐野 晃俊, 嘉数 英二, 井上 淳, 二宮 匡史, 岩田 朋晃, 鶴岡 未央, 佐藤 公亮, 正宗 淳

    日本消化器病学会雑誌　118　(臨増総会)　A359-A359　2021/03

    Publisher: (一財)日本消化器病学会

    ISSN： 0446-6586

    eISSN： 1349-7693

  75. 肝がん診療の現況と課題 肝細胞癌BCLC C期血管内腫瘍栓を有する症例の治療の変化と成績

    二宮 匡史, 岩田 朋晃, 嘉数 英二, 井上 淳, 正宗 淳

    日本消化器病学会東北支部例会プログラム・抄録集　210回　56-56　2021/02

    Publisher: 日本消化器病学会-東北支部

  76. 肝がん診療の現況と課題 肝細胞癌BCLC C期血管内腫瘍栓を有する症例の治療の変化と成績

    二宮 匡史, 岩田 朋晃, 嘉数 英二, 井上 淳, 正宗 淳

    日本消化器病学会東北支部例会プログラム・抄録集　210回　56-56　2021/02

    Publisher: 日本消化器病学会-東北支部

  77. Switching to tenofovir disoproxil fumarate in entecavir-treated chronic hepatitis B patients: A pilot randomized controlled study. International-journal

    Jun Inoue, Takehiro Akahane, Tomoo Kobayashi, Noriyuki Obara, Teruyuki Umetsu, Eiji Kakazu, Masashi Ninomiya, Tomoaki Iwata, Akitoshi Sano, Mio Tsuruoka, Kosuke Sato, Atsushi Masamune

    Biomedical reports　14　(2)　20-20　2021/02

    DOI： 10.3892/br.2020.1396 　

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    Although hepatitis B surface antigen (HBsAg) removal is considered the goal of chronic hepatitis B treatment, it can rarely be achieved with nucleos(t)ide analogues (NAs). It has been reported that tenofovir disoproxil fumarate (TDF) is superior in reducing HBsAg compared with entecavir (ETV) in treatment-naïve patients; however, the effect of TDF in patients who have received NAs is still unclear. The aim of the present study was to evaluate the efficacy of switching from ETV to TDF in patients who were already receiving ETV. A pilot randomized controlled study for 2 years in patients who had been treated with ETV for >1 year and did not exhibit drug resistance was performed (Clinical trial registration: UMIN000021948, UMIN-CTR, May 1, 2016). A total of 20 patients were enrolled and 19 patients were randomized into 2 groups, a TDF-switching group (n=12) or an ETV-continuing group (n=7). The mean change in HBsAg levels after 2 years was greater in the TDF group compared with the ETV group, but the difference was not significant (-0.25 vs. -0.06 log IU/ml). In the TDF group, hepatitis B e antigen (HBeAg)-positive patients at baseline showed significantly greater changes in HBsAg (-0.63 vs. -0.03 log IU/ml; P=0.030). In contrast, no difference between HBeAg-positive and HBeAg-negative patients was observed in the ETV group. No significant differences of estimated glomerular filtration rate and inorganic phosphorus changes were observed among the TDF and ETV groups. In conclusion, a significant HBsAg decrease was not achieved after switching from ETV to TDF in the overall analysis, but HBeAg-positive patients showed a larger HBsAg decrease after switching treatment.

  78. Hepatitis B Virus Reactivation with Discontinuation of Nucleoside Analogue in Patients Who Received Allogeneic Hematopoietic Stem Cell Transplantation

    Mio Tsuruoka, Jun Inoue, Yasushi Onishi, Masashi Ninomiya, Eiji Kakazu, Tomoaki Iwata, Akitoshi Sano, Kosuke Sato, Hideo Harigae, Atsushi Masamune

    Case Reports in Gastroenterology　2021

    DOI： 10.1159/000512397 　

    eISSN： 1662-0631

  79. 自己免疫性肝疾患の難治例に挑む 当院におけるステロイド抵抗性自己免疫性肝炎の特徴

    二宮 匡史, 井上 淳, 正宗 淳

    肝臓　61　(Suppl.3)　A815-A815　2020/11

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  80. 宿敵B型肝炎ウイルスに挑む B型肝炎ウイルス粒子形成におけるCD63の役割に関する検討

    井上 淳, 二宮 匡史, 正宗 淳

    肝臓　61　(Suppl.3)　A838-A838　2020/11

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  81. B型慢性肝炎患者におけるHBVの遺伝子型と患者年齢に関する検討

    佐藤 公亮, 井上 淳, 新妻 宏文, 鶴岡 未央, 佐野 晃俊, 岩田 朋晃, 二宮 匡史, 嘉数 英二, 正宗 淳

    肝臓　61　(Suppl.3)　A861-A861　2020/11

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  82. 門脈血中遊離アミノ酸不均衡は酸化ストレス応答(Keap1-Nrf2 system)を抑制し肝細胞脂肪変性に関与する

    佐野 晃俊, 嘉数 英二, 井上 淳, 二宮 匡史, 岩田 朋晃, 鶴岡 未央, 佐藤 公亮, 小貫 真純, 正宗 淳

    肝臓　61　(Suppl.3)　A875-A875　2020/11

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  83. A validation study of the Ursodeoxycholic Acid Response Score in Japanese patients with primary biliary cholangitis

    Minami Yagi, Kosuke Matsumoto, Atsumasa Komori, Masanori Abe, Naoaki Hashimoto, Mie Inao, Tadashi Namisaki, Kazuhito Kawata, Masashi Ninomiya, Hideki Fujii, Atsushi Takahashi, Jong-Hon Kang, Masaaki Takamura, Mie Arakawa, Satoru Joshita, Ken Sato, Jun Itakura, Takako Nomura, Keisuke Kakisaka, Akira Kaneko, Yamato Tamura, Ryo Miura, Mitsuhiko Aiso, Toshihiko Arizumi, Yoshinari Asaoka, Kentaro Kikuchi, Yasuhiro Takikawa, Tsutomu Masaki, Takeji Umemura, Akira Honda, Hiromasa Ohira, Norifumi Kawada, Hitoshi Yoshiji, Satoshi Mochida, Hajime Takikawa, Atsushi Tanaka

    LIVER INTERNATIONAL　40　(8)　1926-1933　2020/08

    DOI： 10.1111/liv.14534 　

    ISSN： 1478-3223

    eISSN： 1478-3231

  84. Rapid enlargement of a hepatic hilar cyst leading to bile duct obstruction after acute exacerbation of chronic hepatitis B

    Tomoaki Iwata, Jun Inoue, Eiji Kakazu, Masashi Ninomiya, Akitoshi Sano, Mio Tsuruoka, Kiyoshi Kume, Atsushi Masamune

    Clinical Journal of Gastroenterology　2020/07/29

    Publisher: Springer Science and Business Media LLC

    DOI： 10.1007/s12328-020-01189-2 　

    ISSN： 1865-7257

    eISSN： 1865-7265

  85. 肝癌再発過程におけるサルコペニアと血中遊離アミノ酸の関係

    嘉数 英二, 佐野 晃俊, 井上 淳, 二宮 匡史, 岩田 朋晃, 鶴岡 美央, 正宗 淳

    日本消化器病学会雑誌　117　(臨増総会)　A250-A250　2020/07

    Publisher: (一財)日本消化器病学会

    ISSN： 0446-6586

    eISSN： 1349-7693

  86. Lenvatinib治療による肝細胞癌初発からのSequential療法の変化と生存期間の検討

    二宮 匡史, 井上 淳, 嘉数 英二, 岩田 朋晃, 佐野 晃俊, 鶴岡 未央, 正宗 淳

    日本消化器病学会雑誌　117　(臨増総会)　A334-A334　2020/07

    Publisher: (一財)日本消化器病学会

    ISSN： 0446-6586

    eISSN： 1349-7693

  87. 肝癌再発過程におけるサルコペニアと血中遊離アミノ酸の関係

    嘉数 英二, 佐野 晃俊, 井上 淳, 二宮 匡史, 岩田 朋晃, 鶴岡 美央, 正宗 淳

    日本消化器病学会雑誌　117　(臨増総会)　A250-A250　2020/07

    Publisher: (一財)日本消化器病学会

    ISSN： 0446-6586

    eISSN： 1349-7693

  88. Lenvatinib治療による肝細胞癌初発からのSequential療法の変化と生存期間の検討

    二宮 匡史, 井上 淳, 嘉数 英二, 岩田 朋晃, 佐野 晃俊, 鶴岡 未央, 正宗 淳

    日本消化器病学会雑誌　117　(臨増総会)　A334-A334　2020/07

    Publisher: (一財)日本消化器病学会

    ISSN： 0446-6586

    eISSN： 1349-7693

  89. Spontaneous reactivation of hepatitis B virus with S gene mutations in an elderly patient with diabetic nephropathy Peer-reviewed

    Noriyuki Obara, Jun Inoue, Hiroyuki Endo, Eiji Kakazu, Masashi Ninomiya, Tomoaki Iwata, Akitoshi Sano, Mio Tsuruoka, Atsushi Masamune

    Clinical Journal of Gastroenterology　13　(5)　914-919　2020/06/09

    Publisher: Springer Science and Business Media LLC

    DOI： 10.1007/s12328-020-01149-w 　

    ISSN： 1865-7257

    eISSN： 1865-7265

    More details Close

    Generally, reactivation of hepatitis B virus (HBV) infection is induced by the administration of immunosuppressants or anticancer agents, but reactivation without such drugs has rarely been reported. Here we report an elder case with spontaneous reactivation of HBV replication accompanied by hepatitis B surface antigen (HBsAg) mutations. A 69-year-old man with a history of diabetes mellitus and chronic kidney disease (CKD) was found to be positive for HBsAg (0.072 IU/ml) in June 2018. In May 2019, marked hepatic dysfunction and increased HBsAg (2533.2 IU/ml) were observed when he visited the hospital due to diarrhea and worsening of CKD. At that time, hepatitis B surface antibody (HBsAb) was positive (268.9 mIU/ml) and HBV DNA was 6.0 log IU/ml. After treatment with entecavir, HBV DNA and HBsAg rapidly decreased. Full-genome HBV sequence analysis revealed that the patient was infected with HBV of subgenotype B1 and it had an "a" determinant mutation M133L in the S gene coding HBsAg. Notably, both HBsAg and HBsAb were positive at the time of HBV reactivation, suggesting that the HBV with these mutations escaped from neutralization by HBsAb. This case suggests that immune escape mutations could play an important role in spontaneous HBV reactivation.

  90. Effect of viral DNA methylation on expression of hepatitis B virus proteins depends on the virus genotype. International-journal Peer-reviewed

    Takuya Nakamura, Jun Inoue, Masashi Ninomiya, Eiji Kakazu, Tomoaki Iwata, Satoshi Takai, Akitoshi Sano, Takayuki Kogure, Tooru Shimosegawa, Atsushi Masamune

    Virus genes　56　(4)　439-447　2020/05/02

    DOI： 10.1007/s11262-020-01761-5 　

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    The frequency of HBV genomic methylation in the liver was reported to vary among patients, but the detailed mechanism is still unknown. In this study, the effects of HBV genome methylation on HBV replication were investigated in vitro. A total of 6 plasmids containing 1.24-fold the HBV genome of different genotypes (subgenotypes A1, A2, B1, and C2) were purified after in vitro methylation with CpG methyltransferase (M.SssI) and transfected into HepG2 cells. In genotype B and C strains, methylation markedly decreased the amount of hepatitis B e antigen (HBeAg) in the culture supernatant. A reduction of hepatitis B surface antigen (HBsAg) was found in some HBV strains but the reduction was smaller than that of HBeAg. There was no significant difference in particle-associated HBV DNA in the culture supernatant. These findings suggest that HBV genomic methylation might be involved in the HBeAg decline in genotype B and C, in part, and that the reduction of HBsAg was less than that of HBeAg. In conclusion, this study showed that the effect of HBV genomic methylation differs among HBV genotypes, suggesting a potential explanation for the different clinical outcomes of genotypes A, B, and C.

  91. 肝疾患相談室における肝炎医療コーディネーターの活動と課題

    岡村 恵乃, 井上 淳, 嘉数 英二, 二宮 匡史, 岩田 朋晃, 佐野 晃俊, 鶴岡 未央, 正宗 淳

    肝臓　61　(Suppl.1)　A248-A248　2020/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  92. 多発肝細胞癌を伴ったC型非代償性肝硬変に対して選択的DEB-TACEを繰り返しミラノ基準内に抑えることで,生体肝移植までの15ヵ月間待機可能だった一例

    岩田 朋晃, 浅野 優美愛, 井上 淳, 嘉数 英二, 二宮 匡史, 佐野 晃俊, 鶴岡 未央, 宮城 重人, 正宗 淳

    肝臓　61　(Suppl.1)　A271-A271　2020/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  93. 当院における3cm又は3個を超える初発肝細胞癌の穿刺局所治療の成績

    二宮 匡史, 井上 淳, 嘉数 英二, 岩田 朋晃, 佐野 晃俊, 鶴岡 未央, 正宗 淳

    肝臓　61　(Suppl.1)　A403-A403　2020/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  94. 肝細胞癌BCLC A stageで行われた穿刺局所療法と肝動脈塞栓術の治療成績の比較

    二宮 匡史, 井上 淳, 嘉数 英二, 岩田 朋晃, 佐野 晃俊, 鶴岡 未央, 正宗 淳

    肝臓　61　(Suppl.1)　A406-A406　2020/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  95. B型慢性肝疾患に対するETVをTDFに切り替えるランダム化比較試験(多施設共同研究,最終報告)

    井上 淳, 赤羽 武弘, 小林 智夫, 小原 範之, 梅津 輝行, 嘉数 英二, 二宮 匡史, 岩田 朋晃, 佐野 晃俊, 鶴岡 未央, 正宗 淳

    肝臓　61　(Suppl.1)　A420-A420　2020/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  96. 肝癌治療の最前線 Lenvatinib登場後の肝細胞癌初発からのSequential療法の特徴と生存期間の検討

    二宮 匡史, 井上 淳, 嘉数 英二, 岩田 朋晃, 正宗 淳

    日本消化器病学会東北支部例会プログラム・抄録集　208回　67-67　2020/01

    Publisher: 日本消化器病学会-東北支部

  97. 自己免疫性肝炎の経過観察中に認められた肝原発メトトレキセート関連リンパ増殖性疾患の一例

    鶴岡 未央, 井上 淳, 嘉数 英二, 二宮 匡史, 岩田 朋晃, 佐野 晃俊

    日本消化器病学会東北支部例会プログラム・抄録集　208回　128-128　2020/01

    Publisher: 日本消化器病学会-東北支部

  98. Methotrexate-associated Lymphoproliferative Disorder in the Liver Resembling Hepatocellular Carcinoma Treated with Transarterial Chemoembolization Peer-reviewed

    Mio Tsuruoka, Jun Inoue, Eiji Kakazu, Masashi Ninomiya, Tomoaki Iwata, Akitoshi Sano, Atsushi Masamune

    Internal Medicine　59　(18)　2255-2260　2020

    Publisher: Japanese Society of Internal Medicine

    DOI： 10.2169/internalmedicine.4787-20 　

    ISSN： 0918-2918

    eISSN： 1349-7235

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    Methotrexate-related lymphoproliferative disorder (MTX-LPD) is known to be a side effect of MTX, but its involvement in the liver has been rarely reported. We herein report a 70-year-old woman with autoimmune hepatitis and rheumatoid arthritis who developed multiple liver tumors. We initially considered that she had developed rapid-growing hepatocellular carcinoma (HCC) in the cirrhotic liver based on imaging tests. A tumor biopsy and transcatheter arterial chemoembolization were thus performed. The tumors were then diagnosed as diffuse large B-cell lymphoma pathologically and considered to be MTX-LPD. This case indicates that MTX-LPD should be considered even in cirrhotic patients with liver tumors resembling HCC.

  99. The reduction of miR146b-5p in monocytes and T cells could contribute to the immunopathogenesis of hepatitis C virus infection. International-journal Peer-reviewed

    Yasuteru Kondo, Takayuki Kogure, Masashi Ninomiya, Ryo Fukuda, Norikazu Monma, Kazuho Ikeo, Yasuhito Tanaka

    Scientific reports　9　(1)　13393-13393　2019/09/16

    DOI： 10.1038/s41598-019-49706-9 　

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    It has been reported that various kinds of miRNAs could affect the pathogenesis of hepatitis C virus infection. Recently, our group reported that deep-sequencing analysis was useful to detect disease-specific miRNAs. The aim of this study is to identify the HCV-specific miRNAs that could contribute to the immunopathogenesis of HCV by using clinical samples and in vitro analysis. Five miRNAs (hsa-miR181a-2-3p, hsa-miR-374a-3p, hsa-miR374a-5p, hsa-miR-204-5p and hsa-miR146b-5p) were shown to be significantly downregulated in CH-C by deep sequence analysis. The average ratio (PBMCs miRNAs/serum miRNAs) of hsa-miR146b-5p was highest among all the miRNAs. Moreover, serum hsa-miR146b-5p was significantly down-regulated in CH-C patients in comparison to CH-B patients and healthy subjects. The expression of hsa-miR146b-5p in CD3+ T cells and CD14+ monocytes of CH-C patients was significantly lower than that of the other groups. The hsa-miR146b-5p expression in CD14+ monocytes of SVR patients treated with Peg-IFN/RBV was significantly higher than in those of non-SVR patients treated with Peg IFN/RBV. However, the hsa-miR146b-5p expression in CD14+ monocytes of SVR patients treated with DCV and ASV was comparable to that in monocytes of non-SVR patients treated with DCV and ASV. Moreover, the expression levels of hsa-miR146b-5p in CD14+ monocytes were significantly increased after achieving SVR and 1(OH)Vitamin D3 treatment. Further, the expression of HCV-Core could suppress miR146b-5p expression in immune cells and affect the expression of various kinds of cytokines by affecting the NF-κB signaling. In conclusion, the reduction of miR146b-5p in monocytes and T cells could contribute to the immunopathogenesis of hepatitis C virus infection.

  100. Small Interfering RNA Screening for the Small GTPase Rab Proteins Identifies Rab5B as a Major Regulator of Hepatitis B Virus Production. International-journal Peer-reviewed

    Jun Inoue, Masashi Ninomiya, Teruyuki Umetsu, Takuya Nakamura, Takayuki Kogure, Eiji Kakazu, Tomoaki Iwata, Satoshi Takai, Akitoshi Sano, Mitsunori Fukuda, Koichi Watashi, Masanori Isogawa, Yasuhito Tanaka, Tooru Shimosegawa, Mark A McNiven, Atsushi Masamune

    Journal of virology　93　(15)　2019/08/01

    DOI： 10.1128/JVI.00621-19 　

    ISSN： 0022-538X

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    Viruses are considered to use vesicular trafficking in infected cells, but the details of assembly/release pathways of hepatitis B virus (HBV) are still unknown. To identify key regulators of HBV production, we performed short interfering RNA (siRNA) screening for Rab proteins, which are considered to act as molecular switches in vesicular trafficking using HepG2.2.15 cells. Among 62 Rab proteins, the suppression of Rab5B most significantly increased HBV DNA in the culture supernatant. Surprisingly, 5 days after the transfection of Rab5B siRNA, HBV DNA in the supernatant was increased more than 30-fold, reflecting the increase of infectious HBV particles. Northern blotting showed that transcription of 2.4/2.1-kb mRNA coding envelope proteins containing large hepatitis B surface protein (LHBs) was increased. Analysis of hepatocyte nuclear factors (HNFs) showed that transcription of HNF4α, which is known to enhance 2.4-kb mRNA transcription, was regulated by Rab5B. Also, it was revealed that LHBs had accumulated in the endoplasmic reticulum (ER) after Rab5B depletion but not in the multivesicular body (MVB), which is thought to be an organelle utilized for HBV envelope formation. Therefore, it was considered that Rab5B is required for the transport of LHBs from the ER to MVB. Immunofluorescent microscopy showed that HBs proteins, including LHBs, colocalized with HBc in the ER of Rab5B-depleted cells, suggesting that HBV envelopment occurs not only in the MVB but also in the ER. In conclusion, Rab5B is a key regulator of HBV production and could be a target of antiviral therapy.IMPORTANCE HBV infection is a worldwide health problem, but the mechanisms of how HBV utilizes cellular machinery for its life cycle are poorly understood. In particular, it has been unclear how the viral components and virions are transported among the organelles. The HBV budding site has been reported to be the ER or MVB, but it has not been clearly determined. In this study, siRNA-based screening of Rab proteins using HBV-expressing cells showed that Rab5B, one of the Rab5 isoforms, has important roles in late steps of the HBV life cycle. Although Rab5 is known to work on early endosomes, this study showed that Rab5B plays a role in the transport of LHBs between the ER and MVB. Furthermore, it affects the transcription of LHBs. This is the first report on the mechanisms of HBV envelope protein transport among the organelles, and the results provide important insights into the therapeutic control of HBV infection.

  101. 肝硬変患者の骨格筋量と血中遊離アミノ酸の関係

    柘植 駿一, 嘉数 英二, 佐野 晃俊, 井上 淳, 二宮 匡史, 岩田 朋晃, 鶴岡 美央, 正宗 淳

    日本消化器病学会東北支部例会プログラム・抄録集　207回　52-52　2019/07

    Publisher: 日本消化器病学会-東北支部

  102. 造血幹細胞移植後にHBV再活性化予防目的の核酸アナログを中止した3例の検討

    鶴岡 未央, 井上 淳, 嘉数 英二, 二宮 匡史, 岩田 朋晃, 佐野 晃俊, 正宗 淳

    日本消化器病学会東北支部例会プログラム・抄録集　207回　53-53　2019/07

    Publisher: 日本消化器病学会-東北支部

  103. Comparison of hepatitis B virus genotypes B and C among chronically hepatitis B virus-infected patients who received nucleos(t)ide analogs: A multicenter retrospective study. International-journal Peer-reviewed

    Inoue J, Akahane T, Nakayama H, Kimura O, Kobayashi T, Kisara N, Sato T, Morosawa T, Izuma M, Kakazu E, Ninomiya M, Iwata T, Takai S, Nakamura T, Sano A, Niitsuma H, Masamune A, THERME Study Group

    Hepatology research : the official journal of the Japan Society of Hepatology　49　(11)　1263-1274　2019/06

    DOI： 10.1111/hepr.13398 　

    ISSN： 1386-6346

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    AIM: Hepatitis B virus genotype B (HBV/B) has been reported to have less risk of liver cirrhosis and hepatocellular carcinoma (HCC), but long-term observation has rarely been reported. We aimed to clarify the characteristics of HBV/B in nucleos(t)ide analog-treated patients in an area where HBV/B is more prevalent than in other areas of Japan. METHODS: A total of 498 chronically HBV-infected patients treated with nucleos(t)ide analog (lamivudine, entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide fumarate) for >6 months (mean 70.6 months) were included from nine hospitals in northeast Japan. The frequencies of hepatitis B surface antigen loss and HCC occurrence were analyzed. RESULTS: Among 427 patients whose genotype could be determined, 34.0% and 64.4% were infected with HBV/B and genotype C (HBV/C), respectively. The age of patients with HBV/B was significantly older than those with HBV/C (57.7 vs. 48.1). The cumulative rate of hepatitis B surface antigen loss was significantly higher in HBV/B than in HBV/C (3.6% vs. 0.7% at 10 years). Among 480 patients without HCC history, HCC occurrence was found in 40 patients (13.4% at 10 years). There was no cumulative rate difference of HCC occurrence among the genotypes, but after propensity score matching for age/sex, it was significantly lower in HBV/B than in HBV/C (5.3% vs. 18.5% at 10 years). CONCLUSIONS: Although a lower rate of HCC occurrence in HBV/B was shown by an age/sex-matched analysis than that in HBV/C, patients with HBV/B were significantly older and had a comparative risk of HCC occurrence in nucleos(t)ide analog-treated patients.

  104. Acute-onset Autoimmune Hepatitis in a Patient with Selective Immunoglobulin M Deficiency. Peer-reviewed

    Sano A, Inoue J, Kakazu E, Ninomiya M, Iwata T, Morosawa T, Takai S, Nakamura T, Masamune A

    Internal medicine (Tokyo, Japan)　58　(15)　2185-2190　2019/04

    DOI： 10.2169/internalmedicine.2607-18 　

    ISSN： 0918-2918

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    Selective immunoglobulin M deficiency (SIGMD) is an uncommon primary immunodeficiency disorder. We herein report an SIGMD patient with autoimmune hepatitis. A 21-year-old Japanese man was transferred to our hospital because of acute liver dysfunction. His serum IgM level was low, whereas those of IgG and IgA were normal, indicating that he had SIGMD. We diagnosed him with acute-onset autoimmune hepatitis, and his liver function test findings gradually recovered with corticosteroid administration. Although SIGMD with autoimmune diseases has been reported, the clinical features and pathogenesis have not yet been clarified. We have summarized previous reports on SIGMD patients with autoimmune diseases.

  105. Branched chain amino acids are associated with the heterogeneity of the area of lipid droplets in hepatocytes of patients with non-alcoholic fatty liver disease. International-journal Peer-reviewed

    Kakazu E, Sano A, Morosawa T, Inoue J, Ninomiya M, Iwata T, Nakamura T, Takai S, Sawada S, Katagiri H, Shimosegawa T, Masamune A

    Hepatology research : the official journal of the Japan Society of Hepatology　49　(8)　860-871　2019/04

    DOI： 10.1111/hepr.13346 　

    ISSN： 1386-6346

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    AIM: Macrovesicular steatosis around the central vein (zone 3) is one of the pathological features of non-alcoholic fatty liver disease or steatohepatitis (NAFLD/NASH). The aim of this study is to elucidate precisely the association between the area of lipid droplets (LDs) and the plasma metabolic parameters in patients with NAFLD/NASH. METHODS: Eighty patients with NAFLD/NASH diagnosed by needle biopsy were enrolled. The LDs around zone 3 were counted automatically by image processing software, the total area of LDs (TLDs), the maximum area of LDs (MAXLDs), the average area of LDs (AVELDs) and the heterogeneity by the coefficient of variation (CV [%]) were quantified. The correlations between these values and plasma metabolic parameters were analyzed. We evaluated the association between branched chain amino acids (BCAAs) and the heterogeneity of LDs in hepatocytes in vitro and in vivo. RESULTS: The MAXLDs was significantly correlated with more metabolic parameters than AVELDs and TLDs. The level of BCAAs was independently associated with the CV among the metabolic parameters. In early stage NAFLD, aspartate and alanine aminotransferase were significantly higher in the high CV group than in the low CV group. The high concentration of BCAAs increased the CV of LDs in hepatocytes accompanied by the expression of phosphor-p70 S6 kinase and sterol regulatory element-binding protein 1 in vitro. A high BCAA diet induced high heterogeneity of LDs around zone 3 in ob/ob mice. CONCLUSIONS: The levels of BCAAs were associated with the LD heterogeneity of hepatocytes around zone 3 in patients with NAFLD/NASH.

  106. Bezafibrate Improves GLOBE and UK-PBC Scores and Long-Term Outcomes in Patients With Primary Biliary Cholangitis Peer-reviewed

    Akira Honda, Atsushi Tanaka, Tetsuji Kaneko, Atsumasa Komori, Masanori Abe, Mie Inao, Tadashi Namisaki, Naoaki Hashimoto, Kazuhito Kawata, Atsushi Takahashi, Masashi Ninomiya, Jong Hon Kang, Mie Arakawa, Satoshi Yamagiwa, Satoru Joshita, Takeji Umemura, Ken Sato, Akira Kaneko, Kentaro Kikuchi, Jun Itakura, Takako Nomura, Keisuke Kakisaka, Hideki Fujii, Norifumi Kawada, Yasuhiro Takikawa, Tsutomu Masaki, Hiromasa Ohira, Satoshi Mochida, Hitoshi Yoshiji, Satoshi Iimuro, Yasushi Matsuzaki, Hajime Takikawa

    Hepatology　70　(6)　2035-2046　2019/01/01

    DOI： 10.1002/hep.30552 　

    ISSN： 0270-9139

    eISSN： 1527-3350

  107. Cellular Membrane Trafficking Machineries Used by the Hepatitis Viruses. International-journal Peer-reviewed

    Inoue J, Ninomiya M, Shimosegawa T, McNiven MA

    Hepatology (Baltimore, Md.)　68　(2)　751-762　2018/08

    DOI： 10.1002/hep.29785 　

    ISSN： 0270-9139

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    While the life cycles of hepatitis viruses (A, B, C, D, and E) have been modestly characterized, recent intensive studies have provided new insights. Because these viruses "hijack" the membrane trafficking of the host cell machinery during replicative propagation, it is essential to determine and understand these specific cellular pathways. Hepatitis B virus (HBV) and hepatitis C virus are well known as leading causes of liver cirrhosis and hepatocellular carcinoma. While substantial inroads toward treating hepatitis C virus patients have recently been made, patients with HBV continue to require lifelong treatment, which makes a thorough understanding of the HBV life cycle essential. Importantly, these viruses have been observed to "hijack" the secretory and endocytic membrane trafficking machineries of the hepatocyte. These can include the canonical clathrin-mediated endocytic process that internalizes virus through cell surface receptors. While these receptors are encoded by the host genome for normal hepatocellular functions, they also exhibit virus-specific recognition. Further, functions provided by the multivesicular body, which include endosomal sorting complexes required for transport, are now known to envelope a variety of different hepatitis viruses. In this review, we summarize the recent findings regarding the cellular membrane trafficking machineries used by HBV in the context of other hepatitis viruses. (Hepatology 2018; 00:000-000).

  108. The profiling of plasma free amino acids and the relationship between serum albumin and plasma-branched chain amino acids in chronic liver disease: a single-center retrospective study. Peer-reviewed

    Akitoshi Sano, Eiji Kakazu, Tatsuki Morosawa, Jun Inoue, Takayuki Kogure, Masashi Ninomiya, Tomoaki Iwata, Teruyuki Umetsu, Takuya Nakamura, Satoshi Takai, Tooru Shimosegawa

    Journal of gastroenterology　53　(8)　978-988　2018/08

    DOI： 10.1007/s00535-018-1435-5 　

    ISSN： 0944-1174

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    BACKGROUND: It is poorly understood how an imbalance of plasma-free amino acids (PFAAs) occurs and how the imbalance shows an association with the serum albumin (sAlb) level during the progression of chronic liver disease (CLDs). The aim of this study is to elucidate the profiles of PFAAs and the relationship between sAlb and PFAAs in recent patients with CLDs during the progression. METHODS: We retrospectively evaluated the 1569 data of PFAAs data obtained from 908 patients with various CLDs (CHC, CHB. alcoholic, NAFLD/NASH, PBC, AIH, PSC, and cryptogenic). In total, 1140 data of PFAAs could be analyzed in patients with CLDs dependent of their Child-Pugh (CP) score. RESULTS: Various imbalances in PFAAs were observed in each CLDs during the progression. Univariate and multivariate analysis revealed that among 24 PFAAs, the level of plasma-branched chain amino acids (pBCAAs) was significantly associated with the CP score, especially the sAlb score, in patients with chronic hepatitis C virus (CHC), NAFLD/NASH and PBC. The correlation coefficient values between sAlb and pBCAAs-to-Tyrosine ratio (BTR) in these patients were 0.53, 0.53 and 0.79, respectively. Interestingly, although the pBCAAs in NAFLD/NASH patients varied even when the sAlb was within the normal range, the pBCAAs tended to be low when the sAlb was below the normal range. CONCLUSIONS: Although a decrease in the level of pBCAAs was observed during the progression regardless of the CLD etiology, the level of total pBCAAs was independently associated with the sAlb level in the PFAAs of CHC, PBC and NAFLD/NASH. The correlation between sAlb and BTR showed the highest value in PBC patients among the patients with CLDs. A decrease in pBCAAs often occurred in NASH even when the sAlb level was kept in the normal range.

  109. Inhibitory effect of silibinin on hepatitis B virus entry. International-journal Peer-reviewed

    Teruyuki Umetsu, Jun Inoue, Takayuki Kogure, Eiji Kakazu, Masashi Ninomiya, Tomoaki Iwata, Satoshi Takai, Takuya Nakamura, Akitoshi Sano, Tooru Shimosegawa

    Biochemistry and biophysics reports　14　20-25　2018/07

    DOI： 10.1016/j.bbrep.2018.03.003 　

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    Hepatitis B virus (HBV) infection is a worldwide health problem because of its potential to cause liver cirrhosis and hepatocellular carcinoma. Silibinin is a constituent of an extract of milk thistle, which is empirically used as a herbal medicine for the protection of liver, but its detailed effects on HBV are unknown. Because a previous study reported that silibinin hinders clathlin-mediated endocytosis (CME), we aimed to test whether silibinin inhibits the entry of HBV into hepatocytes. Using HepG2-NTCP-C4 cells, which overexpress sodium taurocholate cotransporting polypeptide (NTCP), it was shown that silibinin inhibited HBV infection dose-dependently. Similar effects were observed using human primary hepatocytes (PXB-cells). Additionally, a combination of silibinin and entecavir reduced HBV DNA in the culture supernatant more than either mono-treatment alone in HepG2-NTCP-C4 cells that had already been infected with HBV. Silibinin decreased transferrin uptake but did not affect the interaction between the HBV envelope and NTCP, suggesting that silibinin might inhibit HBV infection by hindering CME. In conclusion, this study showed that silibinin inhibits HBV entry in vitro.

  110. Acute-onset Autoimmune Hepatitis in a Young Woman with Type 1 Diabetes Mellitus. Peer-reviewed

    Satoshi Takai, Jun Inoue, Takayuki Kogure, Eiji Kakazu, Masashi Ninomiya, Tomoaki Iwata, Teruyuki Umetsu, Takuya Nakamura, Akitoshi Sano, Tooru Shimosegawa

    Internal medicine (Tokyo, Japan)　57　(11)　1591-1596　2018/06/01

    DOI： 10.2169/internalmedicine.9728-17 　

    ISSN： 0918-2918

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    Autoimmune hepatitis (AIH) and type 1 diabetes mellitus (T1DM) are thought to be induced by autoimmunity, but their coexistence has rarely been reported. We herein report a case in which a patient with T1DM developed acute-onset AIH. A 26-year-old woman, who had been diagnosed with T1DM in childhood, was transferred to our hospital because of acute liver failure of unknown etiology. The administration of corticosteroids including steroid pulse therapy was effective. Based on the histological finding of massive centrilobular necrosis and a good response to steroid therapy, we diagnosed the patient with acute-onset AIH. This case indicates that AIH can occur in young T1DM patients.

  111. 日本人PBC患者の予後予測におけるGlobeスコア・UK-PBCスコアの妥当性の検証

    田中 篤, 小森 敦正, 阿部 雅則, 稲生 実枝, 浪崎 正, 橋本 直明, 川田 一仁, 高橋 敦史, 二宮 匡史, 藤井 英樹, 本多 彰, 姜 貞憲, 荒川 光江, 山際 訓, 城下 智, 佐藤 賢, 金子 晃, 板倉 潤, 野村 貴子, 柿坂 啓介, 正木 勉, 松崎 靖司, 河田 則文, 大平 弘正, 持田 智, 吉治 仁志, 滝川 一

    肝臓　59　(Suppl.1)　A454-A454　2018/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  112. Identification of Genotype 2 HCV in Serotype-1 Hepatitis C Patients Unresponsive to Daclatasvir plus Asunaprevir Treatment Peer-reviewed

    Jun Inoue, Atsushi Kanno, Yuta Wakui, Masahito Miura, Tomoo Kobayashi, Tatsuki Morosawa, Takayuki Kogure, Eiji Kakazu, Masashi Ninomiya, Yasuyuki Fujisaka, Teruyuki Umetsu, Satoshi Takai, Takuya Nakamura, Tooru Shimosegawa

    TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE　241　(1)　21-28　2017/01

    DOI： 10.1620/tjem.241.21 　

    ISSN： 0040-8727

    eISSN： 1349-3329

  113. Gastroesophageal Variceal Bleeding Successfully Controlled by Partial Splenic Embolization Peer-reviewed

    Takayuki Kogure, Jun Inoue, Eiji Kakazu, Masashi Ninomiya, Tooru Shimosegawa

    INTERNAL MEDICINE　56　(11)　1339-1343　2017

    DOI： 10.2169/internalmedicine.56.8167 　

    ISSN： 0918-2918

    eISSN： 1349-7235

  114. MiR-139-5p is associated with inflammatory regulation through c-FOS suppression, and contributes to the progression of primary biliary cholangitis. International-journal Peer-reviewed

    Tomohiro Katsumi, Masashi Ninomiya, Taketo Nishina, Kei Mizuno, Kyoko Tomita, Hiroaki Haga, Kazuo Okumoto, Takafumi Saito, Tooru Shimosegawa, Yoshiyuki Ueno

    Laboratory investigation; a journal of technical methods and pathology　96　(11)　1165-1177　2016/11

    DOI： 10.1038/labinvest.2016.95 　

    ISSN： 0023-6837

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    Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease characterized pathologically by destruction of intrahepatic bile ducts. PBC is largely classified into three subtypes based on clinical course: (i) gradually progressive, (ii) portal hypertension, and (iii) hepatic failure. Previous studies have indicated that serum levels of the pro-inflammatory cytokine TNF-α, is elevated in PBC patients with fibrosis. Although the severity of cholangitis might also be related to the PBC subtype, its etiology has been unclear. Several studies have shown that microRNAs (miRNAs) demonstrate specific expression patterns in various diseases. In the present study, we evaluated miRNA expression patterns among the PBC subtypes using comprehensive deep sequencing. We also carried out histologic examination by laser capture microdissection and investigated how the identified miRNAs were involved in PBC clinical progression using the miRNA transfection method. On average, ~11 million 32-mer short RNA reads per sample were obtained, and we found that the expression levels of 97 miRNAs differed significantly among the four groups. Heat mapping demonstrated that the miRNA profiles from hepatic failure and portal hypertension type were clustered differently from those of the gradually progressive type and controls. Furthermore, we focused on miR-139-5p, which has an adequate number of total short reads. Quantitative reverse transcription PCR showed that miR-139-5p was significantly downregulated in clinically advanced PBC. Also, examination of liver tissues demonstrated that the expression of lymphocyte-derived miR-139-5p was significantly higher in hepatocytes. In vitro, the level of TNF-α was significantly elevated in supernatant of cells with upregulation of miR-139-5p. Furthermore, c-FOS gene transcription was repressed. Thus, we have demonstrated a novel inflammation-regulatory mechanism involving TNF-α and c-FOS transcription through miR-139-5p in the NF-κB signaling pathway. We conclude that the specific miRNA miR-139-5p might be involved in the pathogenesis of PBC, especially during clinical progression.

  115. The expression of miR-125b-5p is increased in the serum of patients with chronic hepatitis B infection and inhibits the detection of hepatitis B virus surface antigen Peer-reviewed

    M. Ninomiya, Y. Kondo, O. Kimura, R. Funayama, T. Nagashima, T. Kogure, T. Morosawa, Y. Tanaka, K. Nakayama, T. Shimosegawa

    JOURNAL OF VIRAL HEPATITIS　23　(5)　330-339　2016/05

    Publisher: WILEY-BLACKWELL

    DOI： 10.1111/jvh.12522 　

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    MicroRNAs were first discovered as small endogenous RNA molecules and some viruses have been reported to interact with host miRNAs. By investigating miRNA expression in serum derived from HBV-infected patients, we have clarified the relationship between miRNA expression and chronic HBV infection. Additionally, we demonstrate the use of miRNAs as both novel biomarkers and new therapies against HBV. We included the sera of 20 patients with chronic HBV infection, sera of 20 patients with HCV infection and sera of 10 healthy controls in this study. The miRNA libraries were sequenced using a 32-mer single end sequence. The validation study of circulating miRNA in serum was conducted by qRT-PCR. The HBV genomic regions of genotype B and genotype C that were speculated to be targeted by miRNA were constructed using complementary oligonucleotides in the vectors. Reporter assays were performed 48 h after transfection. The expression levels of 21 miRNAs were found to be differentially expressed in the three groups. 10 miRNAs (hsa-miR-100-5p, miR-125b-5p, miR-193b-3p, miR-194-3p, miR-30a-3p, miR-30c-2-3p, miR-3591-5p, miR-4709-3p, miR-574-3p and miR-99a-5p) were found to be upregulated in CH-B by deep sequence analysis. The computer analysis showed that two regions of HBsAg are potential targets of miR-125b-5p and miR-30c-2-3p and that these miRNAs may downregulate the expression of HBV-S. The HBV genotype C segment speculated to be targeted by hsa-miR-125b-5p significantly decreased the expression of the reporter. This study indicated that expression of miR-125b-5p was related to the etiology of chronic hepatitis B infection and regulated the expression of HBsAg.

  116. Radiation Therapy Is a Reasonable Option for Improving the Prognosis in Hepatocellular Carcinoma Peer-reviewed

    Yasuteru Kondo, Osamu Kimura, Takayuki Kogure, Masashi Ninomiya, Rei Umezawa, Toshiyuki Sugawara, Haruo Matsushita, Keiichi Jingu, Yu Nakagome, Tomoaki Iwata, Tatsuki Morosawa, Yasuyuki Fujisaka, Takao Iwasaki, Tooru Shimosegawa

    TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE　237　(4)　249-257　2015/12

    DOI： 10.1620/tjem.237.249 　

    ISSN： 0040-8727

    eISSN： 1349-3329

  117. Differential Expression of CX3CL1 in Hepatitis B Virus-Replicating Hepatoma Cells Can Affect the Migration Activity of CX3CR1(+) Immune Cells Peer-reviewed

    Yasuteru Kondo, Osamu Kimura, Yasuhito Tanaka, Masashi Ninomiya, Tomoaki Iwata, Takayuki Kogure, Jun Inoue, Masaya Sugiyama, Tatsuki Morosawa, Yasuyuki Fujisaka, Tooru Shimosegawa

    JOURNAL OF VIROLOGY　89　(14)　7016-7027　2015/07

    DOI： 10.1128/JVI.00716-15 　

    ISSN： 0022-538X

    eISSN： 1098-5514

  118. HBV secretion is regulated through the activation of endocytic and autophagic compartments mediated by Rab7 stimulation Peer-reviewed

    Jun Inoue, Eugene W. Krueger, Jing Chen, Hong Cao, Masashi Ninomiya, Mark A. McNiven

    JOURNAL OF CELL SCIENCE　128　(9)　1696-1706　2015/05

    DOI： 10.1242/jcs.158097 　

    ISSN： 0021-9533

    eISSN： 1477-9137

  119. 単球細胞におけるmiR146b-5p発現低下は慢性C型肝炎の免疫病態に影響を与える

    近藤 泰輝, 二宮 匡史, 諸沢 樹, 岩田 朋晃, 藤坂 泰之, 小暮 高之, 井上 淳, 中込 悠, 梅津 輝行, 木村 修, 下瀬川 徹

    肝臓　56　(Suppl.1)　A323-A323　2015/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  120. B型肝炎の進展、発癌、ETV/IFN Sequential療法効果に影響を与える因子の同定

    近藤 泰輝, 木村 修, 中込 悠, 新妻 宏文, 二宮 匡史, 小暮 高之, 岩田 朋晃, 諸沢 樹, 藤坂 泰之, 渡辺 大亮, 小林 智夫, 下瀬川 徹

    肝臓　55　(Suppl.2)　A597-A597　2014/09

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  121. 非アルコール性脂肪性肝炎(NASH)患者およびNASHモデルマウスにおける免疫学的検討

    諸沢 樹, 近藤 泰輝, 小暮 高之, 二宮 匡史, 中込 悠, 木村 修, 岩田 朋晃, 藤坂 泰之, 下瀬川 徹

    肝臓　55　(Suppl.2)　A622-A622　2014/09

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  122. 当科における高齢発症自己免疫性肝炎の現状

    中込 悠, 近藤 泰輝, 小暮 高之, 二宮 匡史, 木村 修, 諸沢 樹, 岩田 朋晃, 藤坂 泰之, 下瀬川 徹

    肝臓　55　(Suppl.2)　A677-A677　2014/09

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  123. Involvement of miRNA-29a in epigenetic regulation of transforming growth factor-beta-induced epithelial-mesenchymal transition in hepatocellular carcinoma Peer-reviewed

    Takayuki Kogure, Yasuteru Kondo, Eiji Kakazu, Masashi Ninomiya, Osamu Kimura, Tooru Shimosegawa

    HEPATOLOGY RESEARCH　44　(8)　907-919　2014/08

    DOI： 10.1111/hepr.12188 　

    ISSN： 1386-6346

    eISSN： 1872-034X

  124. Sequential analysis of amino acid substitutions with hepatitis B virus in association with nucleoside/nucleotide analog treatment detected by deep sequencing. International-journal Peer-reviewed

    Masashi Ninomiya, Yasuteru Kondo, Tetsuya Niihori, Takeshi Nagashima, Takayuki Kogure, Eiji Kakazu, Osamu Kimura, Yoko Aoki, Yoichi Matsubara, Tooru Shimosegawa

    Hepatology research : the official journal of the Japan Society of Hepatology　44　(6)　678-84　2014/06

    DOI： 10.1111/hepr.12168 　

    ISSN： 1386-6346

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    Taking nucleoside/nucleotide analogs is a major antiviral therapy for chronic hepatitis B infection. The problem with this treatment is the selection for drug-resistant mutants. Currently, identification of genotypic drug resistance is conducted by molecular cloning sequenced by the Sanger method. However, this methodology is complicated and time-consuming. These limitations can be overcome by deep sequencing technology. Therefore, we performed sequential analysis of the frequency of drug resistance in one individual, who was treated with lamivudine on-and-off therapy for 2 years, by deep sequencing. The lamivudine-resistant mutations at rtL180M and rtM204V and the entecavir-resistant mutation at rtT184L were detected in the first subject. The lamivudine- and entecavir-resistant strain was still detected in the last subject. However, in the deep sequencing analysis, rt180 of the first subject showed a mixture in 76.9% of the methionine and in 23.1% of the leucine, and rt204 also showed a mixture in 69.0% of the valine and 29.8% of the isoleucine. During the treatment, the ratio of resistant mutations increased. At rt184, the resistant variants were detectable in 58.7% of the sequence, with the replacement of leucine by the wild-type threonine in the first subject. Gradually, entecavir-resistant variants increased in 82.3% of the leucine in the last subject. In conclusion, we demonstrated the amino acid substitutions of the serial nucleoside/nucleotide analog resistants. We revealed that drug-resistant mutants appear unchanged at first glance, but actually there are low-abundant mutations that may develop drug resistance against nucleoside/nucleotide analogs through the selection of dominant mutations.

  125. Three cases of adult-onset type II citrullinemia treated with different therapies: Efficacy of sodium pyruvate and low-carbohydrate diet Peer-reviewed

    Takayuki Kogure, Yasuteru Kondo, Eiji Kakazu, Masashi Ninomiya, Osamu Kimura, Nao Kobayashi, Tooru Shimosegawa

    HEPATOLOGY RESEARCH　44　(6)　707-712　2014/06

    DOI： 10.1111/hepr.12170 　

    ISSN： 1386-6346

    eISSN： 1872-034X

  126. HCV Infection Enhances Th17 Commitment, Which Could Affect the Pathogenesis of Autoimmune Diseases Peer-reviewed

    Yasuteru Kondo, Masashi Ninomiya, Osamu Kimura, Keigo Machida, Ryo Funayama, Takeshi Nagashima, Koju Kobayashi, Eiji Kakazu, Takanobu Kato, Keiko Nakayama, Michael M. C. Lai, Tooru Shimosegawa

    PLOS ONE　9　(6)　e98521　2014/06

    DOI： 10.1371/journal.pone.0098521 　

    ISSN： 1932-6203

  127. 診断に苦慮し各種検査から総合的に診断した日本住血吸虫症感染既往の1例

    岩田 朋晃, 近藤 泰輝, 木村 修, 藤島 史喜, 諸沢 樹, 二宮 匡史, 嘉数 英二, 小暮 高之, 岩崎 隆雄, 下瀬川 徹

    日本消化器病学会雑誌　111　(5)　948-955　2014/05

    Publisher: (一財)日本消化器病学会

    ISSN： 0446-6586

    eISSN： 1349-7693

  128. [A case of previous infection with schistosomiasis japonica diagnosed holistically on the basis of various clinical examination findings]. Peer-reviewed

    Tomoaki Iwata, Yasuteru Kondo, Osamu Kimura, Fumiyoshi Fujishima, Tatsuki Morosawa, Masashi Ninomiya, Eiji Kakazu, Takayuki Kogure, Takao Iwasaki, Tooru Shimosegawa

    Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology　111　(5)　948-55　2014/05

    DOI： 10.11405/nisshoshi.111.948 　

    ISSN： 0446-6586

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    A 66-year-old male was referred to our hospital because of a high CRP level. CT and MRI revealed cord-like contrast effects along the periphery of the liver, and peripheral portal vein occlusion was suspected. Histopathological analysis revealed fibrotic occlusion and eosinophil and histiocytic infiltration of the portal vein. Taking into account various clinical imaging tests, blood tests, and histopathological tests and of his current clinical history, he was diagnosed with previous infection of schistosomiasis japonica. We believe that this case illustrates the importance of a comprehensive diagnosis; in addition, we implemented real-time virtual sonography and EOB-MRI that provided useful visual information.

  129. 肝癌におけるmicroRNA-29aおよびDNAメチル化制御を介したEMT誘導の新規機序

    小暮 高之, 近藤 泰輝, 二宮 匡史, 中込 悠, 木村 修, 岩田 朋晃, 諸沢 樹, 藤坂 泰之, 岩崎 隆雄, 下瀬川 徹

    肝臓　55　(Suppl.1)　A228-A228　2014/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  130. CX3CL1-CX3CR1 axisはB型肝炎、肝癌の免疫病態に影響を与える

    近藤 泰輝, 木村 修, 岩田 朋晃, 二宮 匡史, 諸沢 樹, 小暮 高之, 藤坂 泰之, 新妻 宏文, 中込 悠, 下瀬川 徹

    肝臓　55　(Suppl.1)　A259-A259　2014/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  131. 当科における非アルコール性脂肪性肝炎(NASH)患者の免疫学的検討

    諸沢 樹, 近藤 泰輝, 小暮 高之, 二宮 匡史, 中込 悠, 木村 修, 岩田 朋晃, 藤坂 泰之, 下瀬川 徹

    肝臓　55　(Suppl.1)　A366-A366　2014/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  132. 肝特異的microRNA-29aノックアウトマウスを用いた肝線維化の基礎的検討

    小暮 高之, 近藤 泰輝, 二宮 匡史, 中込 悠, 木村 修, 岩田 朋晃, 諸沢 樹, 藤坂 泰之, 岩崎 隆雄, 下瀬川 徹

    日本消化器病学会雑誌　111　(臨増総会)　A249-A249　2014/03

    Publisher: (一財)日本消化器病学会

    ISSN： 0446-6586

    eISSN： 1349-7693

  133. 次世代シークエンサーを用いた核酸アナログ長期使用の耐性B型肝炎ウイルスの解析

    二宮 匡史, 近藤 泰輝, 小暮 高之, 井上 淳, 中込 悠, 木村 修, 諸沢 樹, 岩田 朋晃, 藤坂 泰之, 下瀬川 徹

    日本消化器病学会雑誌　111　(臨増総会)　A336-A336　2014/03

    Publisher: (一財)日本消化器病学会

    ISSN： 0446-6586

    eISSN： 1349-7693

  134. 進行肝細胞癌患者におけるソラフェニブ血中濃度と免疫動態解析

    近藤 泰輝, 岩田 朋晃, 木村 修, 諸沢 樹, 藤坂 泰之, 島田 美樹, 小暮 高之, 二宮 匡史, 下瀬川 徹

    日本消化器病学会雑誌　111　(臨増総会)　A431-A431　2014/03

    Publisher: (一財)日本消化器病学会

    ISSN： 0446-6586

    eISSN： 1349-7693

  135. Eradication of hepatitis C virus could improve immunological status and pyoderma gangrenosum-like lesions Peer-reviewed

    Yasuteru Kondo, Tomoaki Iwata, Takahiro Haga, Osamu Kimura, Masashi Ninomiya, Eiji Kakazu, Takayuki Kogure, Tatsuki Morosawa, Setsuya Aiba, Tooru Shimosegawa

    HEPATOLOGY RESEARCH　44　(2)　238-245　2014/02

    DOI： 10.1111/hepr.12102 　

    ISSN： 1386-6346

    eISSN： 1872-034X

  136. Application of deep sequence technology in hepatology Peer-reviewed

    Masashi Ninomiya, Yoshiyuki Ueno, Tooru Shimosegawa

    HEPATOLOGY RESEARCH　44　(2)　141-148　2014/02

    DOI： 10.1111/hepr.12214 　

    ISSN： 1386-6346

    eISSN： 1872-034X

  137. Discrepant Expression of miR-139-5p Between Serum and Liver in Patients with Primary Biliary Cirrhosis, and its Possible Cellular Origin Peer-reviewed

    Katsumi Tomohiro, Ninomiya Masashi, Tomita Kyoko, Sato Chikako, Okumoto Kazuo, Nishise Yuko, Watanabe Hisayoshi, Saito Takafumi, Ueno Yoshiyuki

    HEPATOLOGY　60　362A　2014

    ISSN： 0270-9139

  138. Expression of EpCAM Increases in the Hepatitis B Related and the Treatment-Resistant Hepatocellular Carcinoma Peer-reviewed

    Osamu Kimura, Yasuteru Kondo, Takayuki Kogure, Eiji Kakazu, Masashi Ninomiya, Tomoaki Iwata, Tatsuki Morosawa, Tooru Shimosegawa

    BIOMED RESEARCH INTERNATIONAL　2014　172913　2014

    DOI： 10.1155/2014/172913 　

    ISSN： 2314-6133

    eISSN： 2314-6141

  139. Plasma amino acids imbalance in cirrhotic patients disturbs the tricarboxylic acid cycle of dendritic cell. International-journal Peer-reviewed

    Eiji Kakazu, Yasuteru Kondo, Takayuki Kogure, Masashi Ninomiya, Osamu Kimura, Yoshiyuki Ueno, Tooru Shimosegawa

    Scientific reports　3　3459-3459　2013/12/10

    DOI： 10.1038/srep03459 　

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    An imbalance of plasma amino acids (AA) is observed cirrhotic patients. Here we report that the imbalance suppresses the maturation of dendritic cells (DCs) by reducing the intracellular ATP due to interference with the mitochondrial tricarboxylic acid (TCA) cycle. We used serum-free culture medium consistent with the average concentration of the plasma AA from a healthy volunteer (HCM) and that from patients with advanced cirrhosis (ACM). We compared the function of DCs and the metabolism of glucose-amino acids under each medium. The maturation and intracellular ATP of immature DCs were lower under ACM in spite of the enhancement of mitochondrial respiratory chain complex genes. Metabolomics revealed that the TCA cycle metabolite, fumarate and 2-oxoglutarate were increased in DCs generated under ACM. Consistent with in vitro, In CD1c(+) or CD14(+) cells from cirrhotic patients, the gene expression of 2-oxoglutarate-succinate-fumarate transition enzymes were significantly different from the cells of healthy controls.

  140. 1(OH)Vit D3 supplementation improves the sensitivity of the immune-response during Peg-IFN/RBV therapy in chronic hepatitis C (CH-C) and CH-C with severe fibrosis Peer-reviewed

    Kondo Yasuteru, Iwata Tomoaki, Morosawa Tatsuki, Kimura Osamu, Ninomiya Masashi, Kakazu Eiji, Kogure Takayuki, Kato Takanobu, Shimosegawa Tooru

    HEPATOLOGY　58　1177A　2013/10

    ISSN： 0270-9139

  141. Lymphotropic HCV infection enhances Th17 commitment, which could affect the pathogenesis of autoimmune and cryoglobuline-related diseases Peer-reviewed

    Kondo Yasuteru, Ninomiya Masashi, Kimura Osamu, Machida Keigo, Funayama Ryo, Nagashima Takeshi, Kobayashi Koju, Kakazu Eiji, Kogure Takayuki, Kato Takanobu, Nakayama Keiko, Shimosegawa Tooru

    HEPATOLOGY　58　1187A-1188A　2013/10

    ISSN： 0270-9139

  142. Ability of miRNA Profiling to Distinguish the Clinical Course of Patients with Primary Biliary Cirrhosis: Comprehensive Analysis with Deep Sequencing Peer-reviewed

    Katsumi Tomohiro, Ninomiya Masashi, Mizuno Kei, Tomita Kyoko, Sato Chikako, Okumoto Kazuo, Nishise Yuko, Watanabe Hisayoshi, Saito Takafumi, Shimosegawa Tooru, Ueno Yoshiyuki

    HEPATOLOGY　58　793A　2013/10

    ISSN： 0270-9139

  143. 自己免疫性肝疾患における血清内microRNAの発現を解析することで病因解明できる可能性がある

    二宮 匡史, 近藤 泰輝, 小暮 高之, 嘉数 英二, 木村 修, 諸沢 樹, 岩田 朋晃, 下瀬川 徹

    肝臓　54　(Suppl.2)　A647-A647　2013/09

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  144. Supplementation of branched-chain amino acids maintains the serum albumin level in the course of hepatocellular carcinoma recurrence. Peer-reviewed

    Eiji Kakazu, Yasuteru Kondo, Takayuki Kogure, Masashi Ninomiya, Osamu Kimura, Tomoaki Iwata, Tatsuki Morosawa, Takao Iwasaki, Tooru Shimosegawa

    The Tohoku journal of experimental medicine　230　(4)　191-6　2013/08

    DOI： 10.1620/tjem.230.191 　

    ISSN： 0040-8727

    eISSN： 1349-3329

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    Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide. Serum albumin (Alb) is an important prognostic factor for patients with HCC. Moreover, plasma levels of branched-chain amino acids (BCAA), L-valine, L-leucine, and L-isoleucine, are commonly decreased in patients with cirrhosis. Accordingly, formulations of BCAA has been used to maintain the Alb level and prevent ascites in patients with cirrhosis. The aim of this study is to investigate differences in the changes in Alb between a group that received a BCAA formulation (n = 29) and a group given a standard diet (n = 60) in the course of HCC recurrences. All patients experienced more than one hospitalization (mean: 2.6; range: 2-10) owing to recurrence. The plasma BCAA concentration and BCAA-to-tyrosine ratio (BTR), which is a good indicator of the severity of hepatic parenchymal injury in patients with cirrhosis, were significantly correlated with Alb. We defined the changes in BCAA and Alb between recurrences as ΔBCAA and ΔAlb, respectively, and stratified the patients in both groups based on number of recurrences (3 < early, 3-5 middle, or 5 > later). There was also a positive correlation between ΔBCAA and ΔAlb. Interestingly, in the group with BCAA, ΔAlb and ΔBCAA were significantly smaller, especially in the middle period (3-5 recurrences), than in the group without BCAA. These results indicate that the BCAA supplementation could maintain the BCAA and Alb levels in the middle period (3-5 recurrences). BCAA formulation is useful for hypoalbuminemia in the course of HCC recurrence.

  145. The influence of pioglitazone on the plasma amino acid profile in patients with nonalcoholic steatohepatitis (NASH) Peer-reviewed

    Eiji Kakazu, Yasuteru Kondo, Masashi Ninomiya, Osamu Kimura, Futoshi Nagasaki, Yoshiyuki Ueno, Tooru Shimosegawa

    HEPATOLOGY INTERNATIONAL　7　(2)　577-585　2013/06

    DOI： 10.1007/s12072-012-9395-y 　

    ISSN： 1936-0533

  146. Distinct MicroRNAs Expression Profile in Primary Biliary Cirrhosis and Evaluation of miR 505-3p and miR197-3p as Novel Biomarkers Peer-reviewed

    Masashi Ninomiya, Yasuteru Kondo, Ryo Funayama, Takeshi Nagashima, Takayuki Kogure, Eiji Kakazu, Osamu Kimura, Yoshiyuki Ueno, Keiko Nakayama, Tooru Shimosegawa

    PLOS ONE　8　(6)　e66086　2013/06

    DOI： 10.1371/journal.pone.0066086 　

    ISSN： 1932-6203

  147. 1(OH) Vitamin D3 Supplementation Improves the Sensitivity of the Immune-Response during Peg-IFN/RBV Therapy in Chronic Hepatitis C Patients-Case Controlled Trial Peer-reviewed

    Yasuteru Kondo, Takanobu Kato, Osamu Kimura, Tomoaki Iwata, Masashi Ninomiya, Eiji Kakazu, Masahito Miura, Takehiro Akahane, Yutaka Miyazaki, Tomoo Kobayashi, Motoyasu Ishii, Norihiro Kisara, Kumiko Sasaki, Haruo Nakayama, Takehiko Igarashi, Noriyuki Obara, Yoshiyuki Ueno, Tatsuki Morosawa, Tooru Shimosegawa

    PLOS ONE　8　(5)　e63672　2013/05

    DOI： 10.1371/journal.pone.0063672 　

    ISSN： 1932-6203

  148. AIH、PBCの最近の進歩 原発性胆汁性肝硬変における血清内miR-505-3pとmiR-197-3pの発現量の低下と、血清内遊離microRNAのプロファイリング

    二宮 匡史, 近藤 泰輝, 下瀬川 徹

    肝臓　54　(Suppl.1)　A37-A37　2013/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  149. 肝硬変に出現する血漿アミノ酸不均衡が樹状細胞機能を抑制するメカニズム

    嘉数 英二, 諸沢 樹, 近藤 泰輝, 二宮 匡史, 木村 修, 岩田 朋晃, 下瀬川 徹

    肝臓　54　(Suppl.1)　A174-A174　2013/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  150. アンチセンスオリゴヌクレオチドを用いたmiR-221発現抑制による肝癌増殖制御 同所移植マウス肝癌モデルを用いたin vivo研究

    小暮 高之, 近藤 泰輝, 嘉数 英二, 二宮 匡史, 木村 修, 岩田 朋晃, 諸沢 樹, 岩崎 隆雄, 下瀬川 徹

    肝臓　54　(Suppl.1)　A259-A259　2013/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  151. 肝細胞癌に誘導されたMyeloid-Derived Suppressor Cells(MDSCs)とPD-L1発現の関係

    岩田 朋晃, 近藤 泰輝, 木村 修, 二宮 匡史, 小暮 高之, 嘉数 英二, 諸沢 樹, 下瀬川 徹

    肝臓　54　(Suppl.1)　A263-A263　2013/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  152. 非アルコール性肝炎(NASH)における線維化の進行と血漿アミノ酸濃度の推移

    諸沢 樹, 嘉数 英二, 近藤 泰輝, 小暮 高之, 二宮 匡史, 木村 修, 岩田 朋晃, 下瀬川 徹

    肝臓　54　(Suppl.1)　A388-A388　2013/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  153. 原発性胆汁性肝硬変における治療前後での血清内microRNAの発現の変化

    二宮 匡史, 近藤 泰輝, 小暮 高之, 嘉数 英二, 木村 修, 舟山 亮, 長嶋 剛史, 中山 啓子, 下瀬川 徹

    日本臨床分子医学会学術総会プログラム・抄録集　50回　68-68　2013/04

    Publisher: 日本臨床分子医学会

  154. Murine Models of Nonalcoholic Fatty Liver Disease and Steatohepatitis. International-journal Peer-reviewed

    Ninomiya M, Kondo Y, Shimosegawa T

    ISRN hepatology　2013　237870-237870　2013

    DOI： 10.1155/2013/237870 　

    More details Close

    In 1980, Ludwig et al. first reported patients of steatohepatitis who lacked a history of excessive alcohol consumption but showed liver histology resembling alcoholic hepatitis and progression to cirrhosis of the liver accompanied by inflammation and fibrosis. The development of nonalcoholic steatohepatitis (NASH) is associated with obesity, diabetes mellitus, insulin resistance, and hyperlipidemia. However, the pathogenesis of NASH remains incomplete. A "multiple-hit" hypothesis for the pathogenesis of NASH based on an animal model has been proposed and remains a foundation for research in this field. We review the important dietary and genetic animal models and discuss the pathogenesis of NASH.

  155. Hepatitis B surface antigen could contribute to the immunopathogenesis of hepatitis B virus infection. Peer-reviewed

    Kondo Y, Ninomiya M, Kakazu E, Kimura O, Shimosegawa T

    ISRN gastroenterology　2013　935295　2013

    DOI： 10.1155/2013/935295 　

    ISSN： 2090-4398

  156. Sequential immunological analysis of HBV/HCV co-infected patients during Peg-IFN/RBV therapy Peer-reviewed

    Yasuteru Kondo, Yoshiyuki Ueno, Masashi Ninomiya, Keiichi Tamai, Yasuhito Tanaka, Jun Inoue, Eiji Kakazu, Koju Kobayashi, Osamu Kimura, Masahito Miura, Takeshi Yamamoto, Tomoo Kobayashi, Takehiko Igarashi, Tooru Shimosegawa

    JOURNAL OF GASTROENTEROLOGY　47　(12)　1323-1335　2012/12

    DOI： 10.1007/s00535-012-0596-x 　

    ISSN： 0944-1174

  157. HCV研究 私の研究とSerendipity 次世代シークエンサーを用いた、C型肝炎ウイルスゲノム解析と血清内microRNAのプロファイリング

    二宮 匡史, 近藤 泰輝, 下瀬川 徹

    肝臓　53　(Suppl.3)　A781-A781　2012/10

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  158. Association between S21 substitution in the core protein of hepatitis B virus and fulminant hepatitis Peer-reviewed

    Jun Inoue, Yoshiyuki Ueno, Kaori Kawamura, Takeshi Yamamoto, Yutaka Mano, Masahito Miura, Tomoo Kobayashi, Hirofumi Niitsuma, Yasuteru Kondo, Eiji Kakazu, Masashi Ninomiya, Osamu Kimura, Noriyuki Obara, Naoki Kawagishi, Yoshitaka Kinouchi, Tooru Shimosegawa

    JOURNAL OF CLINICAL VIROLOGY　55　(2)　147-152　2012/10

    DOI： 10.1016/j.jcv.2012.06.011 　

    ISSN： 1386-6532

    eISSN： 1873-5967

  159. 肝疾患に対する先端医療 次世代シークエンサーを用いて慢性B型肝炎患者血清内の特異的なmiRNAのプロファイリングを行い、新規miRNAの候補を見いだした

    二宮 匡史, 近藤 泰輝, 下瀬川 徹

    肝臓　53　(Suppl.2)　A594-A594　2012/09

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  160. ウイルス性肝炎と肝外病変 Th17分化誘導によるHCV関連自己免疫疾患発症の可能性

    近藤 泰輝, 二宮 匡史, 下瀬川 徹

    肝臓　53　(Suppl.2)　A616-A616　2012/09

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  161. Use of Illumina Deep Sequencing Technology To Differentiate Hepatitis C Virus Variants Peer-reviewed

    Masashi Ninomiya, Yoshiyuki Ueno, Ryo Funayama, Takeshi Nagashima, Yuichiro Nishida, Yasuteru Kondo, Jun Inoue, Eiji Kakazu, Osamu Kimura, Keiko Nakayama, Tooru Shimosegawa

    JOURNAL OF CLINICAL MICROBIOLOGY　50　(3)　857-866　2012/03

    DOI： 10.1128/JCM.05715-11 　

    ISSN： 0095-1137

  162. 非代償性肝硬変における腎機能低下の要因

    嘉数英二, 近藤泰輝, 二宮匡史, 木村修, 下瀬川徹

    消化器内科　54　(3)　380-385　2012

    Publisher:

    ISSN： 1884-2895

  163. 各種肝疾患における免疫機能異常発生の新規メカニズム提唱と解析

    近藤泰輝, 嘉数英二, 二宮匡史, 木村修, 岩崎隆雄, 上野義之, 下瀬川徹

    分子生物が可能とした個別化医療　2012

  164. PBC: Animal Models of Cholangiopathies and Possible Endogenous Viral Infections. International-journal Peer-reviewed

    Ninomiya M, Ueno Y, Shimosegawa T

    International journal of hepatology　2012　649290-649290　2012

    DOI： 10.1155/2012/649290 　

    ISSN： 2090-3448

    More details Close

    Primary Biliary Cirrhosis (PBC) is considered an autoimmune disease characterized by immune-mediated destruction of the intrahepatic bile ducts and its characteristic serologic marker, the anti-mitochondrial antibody (AMA). Several factors were proposed to clarify the pathological and immunological mechanisms of PBC. Immunological reaction with a bacterial or a viral association was identified in the previous report, and it seems probable that PBC was thought to have such an etiology. The majority of patients with PBC was reported to have both RT-PCR and immunohistochemistry evidence of human betaretrovirus infection in lymph nodes or in 2008, the patient who developed PBC with high HIV viral load had an antiviral therapy and recovered. To understand the etiology of PBC associated with infection, several factors should be considered and especially animal models may be useful. In this paper, we introduce three typical animal models of PBC: the dominant-negative form of transforming growth factor-β receptor type II (dnTGFβRII) mouse, IL-2Rα(-/-) mouse and NOD.c3c4 mouse, are enumerated and described, and we discuss previous reports of viral infection associated with PBC and consider the etiology of PBC from our analysis of results in NOD.c3c4 mouse.

  165. Rapid reduction of hepatitis C virus-Core protein in the peripheral blood improve the immunological response in chronic hepatitis C patients Peer-reviewed

    Yasuteru Kondo, Yoshiyuki Ueno, Yuta Wakui, Masashi Ninomiya, Eiji Kakazu, Jun Inoue, Koju Kobayashi, Noriyuki Obara, Tooru Shimosegawa

    HEPATOLOGY RESEARCH　41　(12)　1153-1168　2011/12

    DOI： 10.1111/j.1872-034X.2011.00878.x 　

    ISSN： 1386-6346

  166. Enhanced Replication of Hepatitis B Virus With Frameshift in the Precore Region Found in Fulminant Hepatitis Patients Peer-reviewed

    Jun Inoue, Yoshiyuki Ueno, Yuta Wakui, Koji Fukushima, Yasuteru Kondo, Eiji Kakazu, Masashi Ninomiya, Hirofumi Niitsuma, Tooru Shimosegawa

    JOURNAL OF INFECTIOUS DISEASES　204　(7)　1017-1025　2011/10

    DOI： 10.1093/infdis/jir485 　

    ISSN： 0022-1899

  167. Plasma L-Cystine/L-Glutamate Imbalance Increases Tumor Necrosis Factor-Alpha from CD14+Circulating Monocytes in Patients with Advanced Cirrhosis Peer-reviewed

    Eiji Kakazu, Yoshiyuki Ueno, Yasuteru Kondo, Jun Inoue, Masashi Ninomiya, Osamu Kimura, Yuta Wakui, Koji Fukushima, Keiichi Tamai, Tooru Shimosegawa

    PLOS ONE　6　(8)　e23402　2011/08

    DOI： 10.1371/journal.pone.0023402 　

    ISSN： 1932-6203

  168. The Nutritional Index 'CONUT' Is Useful for Predicting Long-Term Prognosis of Patients with End-Stage Liver Diseases Peer-reviewed

    Koji Fukushima, Yoshiyuki Ueno, Naoki Kawagishi, Yasuteru Kondo, Jun Inoue, Eiji Kakazu, Masashi Ninomiya, Yuta Wakui, Naoko Saito, Susumu Satomi, Tooru Shimosegawa

    TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE　224　(3)　215-219　2011/07

    DOI： 10.1620/tjem.224.215 　

    ISSN： 0040-8727

    eISSN： 1349-3329

  169. Hepatitis B virus replication could enhance regulatory T cell activity by producing soluble heat shock protein 60 from hepatocytes Peer-reviewed

    Yasuteru Kondo, Yoshiyuki Ueno, Koju Kobayashi, Eiji Kakazu, Masaaki Shiina, Jun Inoue, Keiichi Tamai, Yuta Wakui, Yasuhito Tanaka, Masashi Ninomiya, Noriyuki Obara, Koji Fukushima, Motoyasu Ishii, Tomoo Kobayashi, Hirofumi Niitsuma, Satonori Kon, Tooru Shimosegawa

    Journal of Infectious Diseases　202　(2)　202-213　2010/07/15

    DOI： 10.1086/653496 　

    ISSN： 0022-1899

  170. Hepatitis B Virus Replication Could Enhance Regulatory T Cell Activity by Producing Soluble Heat Shock Protein 60 From Hepatocytes Peer-reviewed

    Yasuteru Kondo, Yoshiyuki Ueno, Koju Kobayashi, Eiji Kakazu, Masaaki Shiina, Jun Inoue, Keiichi Tamai, Yuta Wakui, Yasuhito Tanaka, Masashi Ninomiya, Noriyuki Obara, Koji Fukushima, Motoyasu Ishii, Tomoo Kobayashi, Hirofumi Niitsuma, Satonori Kon, Tooru Shimosegawa

    JOURNAL OF INFECTIOUS DISEASES　202　(2)　202-213　2010/07

    DOI： 10.1086/653496 　

    ISSN： 1537-6613

  171. Branched Chain Amino Acids Enhance the Maturation and Function of Myeloid Dendritic Cells Ex Vivo in Patients with Advanced Cirrhosis Peer-reviewed

    Eiji Kakazu, Yoshiyuki Ueno, Yasuteru Kondo, Koji Fukushima, Masaaki Shiina, Jun Inoue, Keiichi Tamai, Masashi Ninomiya, Tooru Shimosegawa

    HEPATOLOGY　50　(6)　1936-1945　2009/12

    DOI： 10.1002/hep.23248 　

    ISSN： 0270-9139

  172. Sporadic acute hepatitis E occurred constantly during the last decade in northeast Japan Peer-reviewed

    Jun Inoue, Yoshiyuki Ueno, Futoshi Nagasaki, Takehiro Akahane, Koji Fukushima, Takayuki Kogure, Yasuteru Kondo, Eiji Kakazu, Keiichi Tamai, Osamu Kido, Yu Nakagome, Masashi Ninomiya, Noriyuki Obara, Yuta Wakui, Masaharu Takahashi, Hiroaki Okamoto, Tooru Shimosegawa

    JOURNAL OF GASTROENTEROLOGY　44　(4)　329-337　2009/04

    DOI： 10.1007/s00535-009-0012-3 　

    ISSN： 0944-1174

    eISSN： 1435-5922

  173. Analysis of the entire genomes of torque teno midi virus variants in chimpanzees: infrequent cross-species infection between humans and chimpanzees Peer-reviewed

    Masashi Ninomiya, Masaharu Takahashi, Yu Hoshino, Koji Ichiyama, Peter Simmonds, Hiroaki Okamoto

    JOURNAL OF GENERAL VIROLOGY　90　(Pt 2)　347-358　2009/02

    DOI： 10.1099/vir.0.007385-0 　

    ISSN： 0022-1317

  174. Transient elastography for measurement of liver stiffness measurement can detect early significant hepatic fibrosis in Japanese patients with viral and nonviral liver diseases Peer-reviewed

    Noriyuki Obara, Yoshiyuki Ueno, Koji Fukushima, Yu Nakagome, Eiji Kakazu, Osamu Kimura, Yuta Wakui, Osamu Kido, Masashi Ninomiya, Takayuki Kogure, Jun Inoue, Yasuteru Kondo, Masaaki Shiina, Takao Iwasaki, Takeshi Yamamoto, Tooru Shimosegawa

    JOURNAL OF GASTROENTEROLOGY　43　(9)　720-728　2008/09

    DOI： 10.1007/s00535-008-2225-2 　

    ISSN： 0944-1174

  175. Development of PCR assays with nested primers specific for differential detection of three human anelloviruses and early acquisition of dual or triple infection during infancy Peer-reviewed

    Masashi Ninomiya, Masaharu Takahashi, Tsutomu Nishizawa, Tooru Shimosegawa, Hiroaki Okamoto

    JOURNAL OF CLINICAL MICROBIOLOGY　46　(2)　507-514　2008/02

    DOI： 10.1128/JCM.01703-07 　

    ISSN： 0095-1137

  176. Complete remission of a case of hepatocellular carcinoma with tumor invasion in inferior vena cava and with pulmonary metastasis successfully treated with repeated arterial infusion chemotherapy Peer-reviewed

    Takayuhi Kogure, Takao Iwasaki, Yoshiyuki Ueno, Noriatsu Kanno, Koji Fukushima, Yoko Yamagiwa, Futoshi Nagasaki, Eiji Kakazu, Yasunori Matsuda, Osamu Kido, Yu Nakagome, Masashi Ninomiya, Tooru Shimosegawa

    HEPATO-GASTROENTEROLOGY　54　(79)　2113-2116　2007/10

    ISSN： 0172-6390

  177. Prevalence of hepatitis B, C, and delta virus infections among children in Mongolia: Progress in childhood immunization Peer-reviewed

    Bira Tsatsralt-Od, Masaharu Takahashi, Kazunori Endo, Dondog Agiimaa, Osorjin Buyankhuu, Masashi Ninomiya, Felipe R. Lorenzo, Hiroaki Okamoto

    JOURNAL OF MEDICAL VIROLOGY　79　(8)　1064-1074　2007/08

    DOI： 10.1002/jmv.20867 　

    ISSN： 0146-6615

  178. Identification of genotype 4 hepatitis E virus strains from a patient with acute hepatitis E and farm pigs in Bali, Indonesia Peer-reviewed

    I. Dewa Nyoman Wibawa, I. G. A. Suryadarma, Mulyanto, Fumio Tsuda, Yasunobu Matsumoto, Masashi Ninomiya, Masaharu Takahashi, Hiroaki Okamoto

    JOURNAL OF MEDICAL VIROLOGY　79　(8)　1138-1146　2007/08

    DOI： 10.1002/jmv.20904 　

    ISSN： 0146-6615

  179. Identification and genomic characterization of a novel human torque teno virus of 3.2 kb Peer-reviewed

    Masashi Ninomiya, Tsutomu Nishizawa, Masaharu Takahashi, Felipe R. Lorenzo, Tooru Shimosegawa, Hiroaki Okamoto

    JOURNAL OF GENERAL VIROLOGY　88　(Pt 7)　1939-1944　2007/07

    DOI： 10.1099/vir.0.82895-0 　

    ISSN： 0022-1317

  180. Sustained viral response of a case of acute hepatitis C virus infection via needle-stick injury Peer-reviewed

    Takayuki Kogure, Yoshiyuki Ueno, Noriatsu Kanno, Koji Fukushima, Yoko Yamagiwa, Futoshi Nagasaki, Eiji Kakazu, Yasunori Matsuda, Osamu Kido, Yu Nakagome, Masashi Ninomiya, Tooru Shimosegawa

    WORLD JOURNAL OF GASTROENTEROLOGY　12　(29)　4757-4760　2006/08

    ISSN： 1007-9327

  181. The effect of branched chain amino acid formulation on keeping the serum albumin level in the course of hepatocellular carcinoma recurrence. Peer-reviewed

    Kakazu E, Kondo Y, Kogure T, Ninomiya M, Kimura O, Iwata T, Morosawa T, Iwasaki T, Shimosegawa T

    Tohoku J Exp Med. 2013;230(4):191-6.

    DOI： 10.1620/tjem.230.191 　

Show all ︎Show first 5

Misc. 123

  1. 非代償性肝硬変による難治性腹水患者におけるCARTの有効性・安全性の検討

    鶴岡未央, 井上淳, 二宮匡史, 佐野晃俊, 佐藤公亮, 小貫真純, 澤橋里子, 大内啓志, 正宗淳

    日本消化器病学会雑誌(Web)　121　2024

    ISSN： 1349-7693

  2. Lenvatinib投与後における肝細胞癌の病理学的変化とその後の治療効果判定

    二宮匡史, 鶴岡未央, 井上淳, 佐野晃俊, 佐藤公亮, 小貫真純, 澤橋里子, 大内啓志, 正宗淳

    日本消化器病学会雑誌(Web)　121　2024

    ISSN： 1349-7693

  3. Prognostic value of serum ALP levels during additional treatment in Japanese patients with primary biliary cholangitis treated with ursodeoxycholic acid and bezafibrate

    Akihito Takeuchi, Kosuke Matsumoto, Atsumasa Komori, Masanori Abe, Tadashi Namisaki, Kazuhito Kawata, Masashi Ninomiya, Hideki Fujii, Atsushi Takahashi, Kang Jong-Hon, Masaaki Takamura, Mie Arakawa, Satoru Joshita, Ken Sato, Takako Nomura, Keisuke Kakisaka, Akira Kaneko, Kentaro Kikuchi, Tsutomu Masaki, Takeji Umemura, Akira Honda, Hiromasa Ohira, Norifumi Kawada, Hitoshi Yoshiji, Satoshi Mochida, Atsushi Tanaka

    JOURNAL OF HEPATOLOGY　78　S394-S395　2023/06

    ISSN： 0168-8278

    eISSN： 1600-0641

  4. 研究者の最新動向 B型肝炎ウイルスと小胞輸送の関わり

    井上 淳, 二宮 匡史, 正宗 淳

    Precision Medicine　2　(10)　971-975　2019/09

    Publisher: (株)北隆館

    ISSN： 2434-3625

  5. 肝硬変患者の骨格筋量と血中遊離アミノ酸の関係

    柘植 駿一, 嘉数 英二, 佐野 晃俊, 井上 淳, 二宮 匡史, 岩田 朋晃, 鶴岡 美央, 正宗 淳

    日本消化器病学会東北支部例会プログラム・抄録集　207回　52-52　2019/07

    Publisher: 日本消化器病学会-東北支部

  6. 造血幹細胞移植後にHBV再活性化予防目的の核酸アナログを中止した3例の検討

    鶴岡 未央, 井上 淳, 嘉数 英二, 二宮 匡史, 岩田 朋晃, 佐野 晃俊, 正宗 淳

    日本消化器病学会東北支部例会プログラム・抄録集　207回　53-53　2019/07

    Publisher: 日本消化器病学会-東北支部

  7. 新たなB型肝炎治療薬:創薬の現況 B型肝炎ウイルスに対するミリストイル化阻害の治療応用の可能性

    井上 淳, 二宮 匡史, 正宗 淳

    肝臓　60　(Suppl.1)　A182-A182　2019/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

  8. 門脈血中遊離アミノ酸に注目した非アルコール性脂肪性肝疾患(NAFLD)の病態解明

    佐野 晃俊, 嘉数 英二, 諸沢 樹, 井上 淳, 二宮 匡史, 岩田 朋晃, 高井 智, 中村 琢也, 下瀬川 徹, 正宗 淳

    肝臓　60　(Suppl.1)　A338-A338　2019/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  9. 非アルコール性脂肪性肝疾患(NAFLD)において分岐鎖アミノ酸(BCAA)は肝細胞脂肪変性のheterogeneityに関与する

    嘉数 英二, 佐野 晃俊, 諸沢 樹, 井上 淳, 二宮 匡史, 岩田 朋晃, 高井 智, 中村 琢也, 正宗 淳

    肝臓　60　(Suppl.1)　A339-A339　2019/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  10. 当院のおけるSorafenib治療成績の特徴とLenvatinib初期治療成績

    二宮 匡史, 井上 淳, 正宗 淳

    肝臓　60　(Suppl.1)　A486-A486　2019/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

  11. HCV肝癌治療後の再発予測因子とDAAによる治療後の再発肝癌の特徴

    二宮 匡史, 井上 淳, 正宗 淳

    肝臓　60　(Suppl.1)　A515-A515　2019/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

  12. C型肝炎ウイルス駆除後の肝発癌の現状と対策 肝細胞癌治療後DAAにてC型肝炎を治療した症例の肝細胞癌再発の検討

    二宮 匡史, 井上 淳, 正宗 淳

    日本消化器病学会雑誌　116　(臨増総会)　A124-A124　2019/03

    Publisher: (一財)日本消化器病学会

    ISSN： 0446-6586

  13. B型肝炎の根治を目指した臨床及び創薬研究最前線 Rab5BによるHBV粒子放出制御メカニズムの解明と治療応用に向けた検討

    井上 淳, 二宮 匡史, 正宗 淳

    日本消化器病学会雑誌　116　(臨増総会)　A201-A201　2019/03

    Publisher: (一財)日本消化器病学会

    ISSN： 0446-6586

  14. 非アルコール性脂肪性肝疾患(NAFLD)の肝脂肪変性に関与する門脈血中遊離アミノ酸の研究

    佐野 晃俊, 嘉数 英二, 井上 淳, 二宮 匡史, 岩田 朋晃, 高井 智, 中村 琢也, 下瀬川 徹, 正宗 淳

    日本消化器病学会雑誌　116　(臨増総会)　A266-A266　2019/03

    Publisher: (一財)日本消化器病学会

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    eISSN： 1349-7693

  15. 目指せ!消化器病専門医-初期研修医からの報告 ステロイド投与によりHCVが再活性化して黄疸を呈したがDAAにより加療できたC型慢性肝炎の一例

    釜野 大典, 井上 淳, 嘉数 英二, 二宮 匡史, 中村 琢也, 高井 智, 岩田 朋晃, 佐野 晃俊, 正宗 淳

    日本消化器病学会東北支部例会プログラム・抄録集　206回　64-64　2019/02

    Publisher: 日本消化器病学会-東北支部

  16. 当科での切除不能肝細胞癌に対するレンバチニブ使用成績

    岩田 朋晃, 井上 淳, 嘉数 英二, 二宮 匡史, 高井 智, 中村 拓也, 佐野 晃俊, 正宗 淳

    日本消化器病学会東北支部例会プログラム・抄録集　206回　81-81　2019/02

    Publisher: 日本消化器病学会-東北支部

  17. B型慢性肝疾患に対するETVをTDFに切り替えるランダム化比較試験(多施設共同研究、中間解析)

    井上 淳, 赤羽 武弘, 小林 智夫, 小原 範之, 梅津 輝行, 嘉数 英二, 二宮 匡史, 岩田 朋晃, 高井 智, 中村 琢也, 佐野 晃俊, 正宗 淳

    肝臓　59　(Suppl.3)　A967-A967　2018/11

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

  18. 【慢性炎症から肝胆膵癌にいたるランドスケープ】 肝臓 B型肝炎ウイルスの感染から肝細胞癌に至るまでのメカニズム B型肝炎による肝癌はなぜ減らないのか

    井上 淳, 二宮 匡史, 正宗 淳

    肝・胆・膵　77　(3)　625-629　2018/09

    Publisher: (株)アークメディア

    ISSN： 0389-4991

  19. 造血幹細胞移植患者におけるB型肝炎ウイルスの再活性化の検討

    井上 淳, 二宮 匡史, 嘉数 英二, 岩田 朋晃, 梅津 輝行, 高井 智, 中村 琢也, 佐野 晃俊, 正宗 淳

    肝臓　59　(Suppl.2)　A662-A662　2018/09

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

  20. 肝細胞癌RFA焼灼療法後の再発に関連する因子の検討

    二宮 匡史, 井上 淳, 嘉数 英二, 岩田 朋晃, 高井 智, 中村 琢也, 佐野 晃俊, 正宗 淳

    肝臓　59　(Suppl.2)　A689-A689　2018/09

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

  21. 外来通院中の慢性肝疾患患者における症状の解析

    中村 琢也, 井上 淳, 佐野 晃俊, 高井 智, 岩田 朋晃, 二宮 匡史, 嘉数 英二, 正宗 淳

    肝臓　59　(Suppl.2)　A718-A718　2018/09

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

  22. 【慢性炎症から肝胆膵癌にいたるランドスケープ】 肝臓 B型肝炎ウイルスの感染から肝細胞癌に至るまでのメカニズム B型肝炎による肝癌はなぜ減らないのか

    井上 淳, 二宮 匡史, 正宗 淳

    肝・胆・膵　77　(3)　625-629　2018/09

    Publisher: (株)アークメディア

    ISSN： 0389-4991

  23. 造血幹細胞移植患者におけるB型肝炎ウイルスの再活性化の検討

    井上 淳, 二宮 匡史, 嘉数 英二, 岩田 朋晃, 梅津 輝行, 高井 智, 中村 琢也, 佐野 晃俊, 正宗 淳

    肝臓　59　(Suppl.2)　A662-A662　2018/09

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

  24. 肝細胞癌RFA焼灼療法後の再発に関連する因子の検討

    二宮 匡史, 井上 淳, 嘉数 英二, 岩田 朋晃, 高井 智, 中村 琢也, 佐野 晃俊, 正宗 淳

    肝臓　59　(Suppl.2)　A689-A689　2018/09

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

  25. 外来通院中の慢性肝疾患患者における症状の解析

    中村 琢也, 井上 淳, 佐野 晃俊, 高井 智, 岩田 朋晃, 二宮 匡史, 嘉数 英二, 正宗 淳

    肝臓　59　(Suppl.2)　A718-A718　2018/09

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

  26. 日本人PBC患者の予後予測におけるGlobeスコア・UK-PBCスコアの妥当性の検証

    田中 篤, 小森 敦正, 阿部 雅則, 稲生 実枝, 浪崎 正, 橋本 直明, 川田 一仁, 高橋 敦史, 二宮 匡史, 藤井 英樹, 本多 彰, 姜 貞憲, 荒川 光江, 山際 訓, 城下 智, 佐藤 賢, 金子 晃, 板倉 潤, 野村 貴子, 柿坂 啓介, 正木 勉, 松崎 靖司, 河田 則文, 大平 弘正, 持田 智, 吉治 仁志, 滝川 一

    肝臓　59　(Suppl.1)　A454-A454　2018/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

  27. 肝臓領域の基礎研究における新しい潮流と臨床応用 B型肝炎ウイルスと小胞輸送システムのクロストーク

    井上 淳, 二宮 匡史, 正宗 淳

    肝臓　59　(Suppl.1)　A169-A169　2018/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

  28. 肝硬変の成因別実態 東北大学消化器内科入院患者における過去十年の肝硬変成因の推移と疾患別特徴

    嘉数 英二, 佐野 晃俊, 井上 淳, 二宮 匡史, 岩田 朋晃, 梅津 輝行, 高井 智, 中村 琢也, 正宗 淳, 下瀬川 徹

    肝臓　59　(Suppl.1)　A277-A277　2018/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

  29. HBV genomeのメチル化がHBVタンパクの発現に与える影響

    中村 琢也, 井上 淳, 佐野 晃俊, 高井 智, 梅津 輝行, 岩田 朋晃, 二宮 匡史, 嘉数 英二, 正宗 淳, 下瀬川 徹

    肝臓　59　(Suppl.1)　A313-A313　2018/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

  30. C型慢性肝炎におけるSVR前後での非侵襲的肝線維化評価についての検討

    高井 智, 井上 淳, 佐野 晃俊, 中村 琢也, 梅津 輝行, 岩田 朋晃, 二宮 匡史, 嘉数 英二, 正宗 淳

    肝臓　59　(Suppl.1)　A316-A316　2018/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

  31. 門脈血類似灌流培養による肝細胞脂肪変性に関する遊離アミノ酸の検討

    佐野 晃俊, 嘉数 英二, 井上 淳, 二宮 匡史, 岩田 朋晃, 梅津 輝行, 高井 智, 中村 琢也, 正宗 淳, 下瀬川 徹

    肝臓　59　(Suppl.1)　A356-A356　2018/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

  32. 肝臓領域の基礎研究における新しい潮流と臨床応用 B型肝炎ウイルスと小胞輸送システムのクロストーク

    井上 淳, 二宮 匡史, 正宗 淳

    肝臓　59　(Suppl.1)　A169-A169　2018/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

  33. 肝硬変の成因別実態 東北大学消化器内科入院患者における過去十年の肝硬変成因の推移と疾患別特徴

    嘉数 英二, 佐野 晃俊, 井上 淳, 二宮 匡史, 岩田 朋晃, 梅津 輝行, 高井 智, 中村 琢也, 正宗 淳, 下瀬川 徹

    肝臓　59　(Suppl.1)　A277-A277　2018/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

  34. HBV genomeのメチル化がHBVタンパクの発現に与える影響

    中村 琢也, 井上 淳, 佐野 晃俊, 高井 智, 梅津 輝行, 岩田 朋晃, 二宮 匡史, 嘉数 英二, 正宗 淳, 下瀬川 徹

    肝臓　59　(Suppl.1)　A313-A313　2018/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

  35. C型慢性肝炎におけるSVR前後での非侵襲的肝線維化評価についての検討

    高井 智, 井上 淳, 佐野 晃俊, 中村 琢也, 梅津 輝行, 岩田 朋晃, 二宮 匡史, 嘉数 英二, 正宗 淳

    肝臓　59　(Suppl.1)　A316-A316　2018/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

  36. 門脈血類似灌流培養による肝細胞脂肪変性に関する遊離アミノ酸の検討

    佐野 晃俊, 嘉数 英二, 井上 淳, 二宮 匡史, 岩田 朋晃, 梅津 輝行, 高井 智, 中村 琢也, 正宗 淳, 下瀬川 徹

    肝臓　59　(Suppl.1)　A356-A356　2018/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

  37. The expression of serum miR-125b-5p may serve as a new biomarker of the HBV-infected hepatitis progression

    Masashi Ninomiya, Jun Inoue, Eiji Kakazu, Tomoaki Iwata, Teruyuki Umetsu, Satoshi Takai, Takuya Nakamura, Akitoshi Sano, Tooru Shimosegawa

    HEPATOLOGY　66　797A-798A　2017/10

    ISSN： 0270-9139

    eISSN： 1527-3350

  38. Dysregulation and functional roles of microRNA-133b in hepatocellular carcinoma

    Takayuki Kogure, Jun Inoue, Eiji Kakazu, Masashi Ninomiya, Tomoaki Iwata, Teruyuki Umetsu, Satoshi Takai, Takuya Nakamura, Tooru Shimosegawa, Kennichi Satoh

    HEPATOLOGY　66　374A-374A　2017/10

    ISSN： 0270-9139

    eISSN： 1527-3350

  39. The relationship between the plasma free amino acids and the pathological features in nonalcoholic fatty liver disease (NAFLD)

    Eiji Kakazu, Akitoshi Sano, Tatsuki Morosawa, Satoshi Takai, Takuya Nakamura, Teruyuki Umetsu, Tomoaki Iwata, Masashi Ninomiya, Takayuki Kogure, Jun Inoue, Tooru Shimosegawa

    HEPATOLOGY　66　1164A-1165A　2017/10

    ISSN： 0270-9139

    eISSN： 1527-3350

  40. Rab5B determines HBV release pathways by promoting transport of LHBs from ER to MVB

    Jun Inoue, Teruyuki Umetsu, Takuya Nakamura, Masashi Ninomiya, Takayuki Kogure, Eiji Kakazu, Tomoaki Iwata, Tatsuki Morosawa, Satoshi Takai, Akitoshi Sano, Yasuhito Tanaka, Tooru Shimosegawa

    HEPATOLOGY　66　796A-796A　2017/10

    ISSN： 0270-9139

    eISSN： 1527-3350

  41. A case of erythropoietic protoporphyria who was diagnosed genetically and whose serial liver specimens showed significant progression of fibrosis

    Nakamura Takuya, Shimosegawa Tooru, Inoue Jun, Kogure Takayuki, Kakazu Eiji, Ninomiya Masashi, Morosawa Tatsuki, Umetsu Teruyuki, Takai Satoshi, Nakano Hajime

    Kanzo　58　(5)　289-295　2017

    Publisher: The Japan Society of Hepatology

    DOI： 10.2957/kanzo.58.289 　

    ISSN： 0451-4203

    More details Close

    &lt;p&gt;A 48-year-old man with liver dysfunction was referred to our hospital and was hospitalized for diagnosis in March 2016. He had been pointed our liver dysfunction since 2006 and liver biopsy was performed in another hospital in October 2014, but the cause of liver dysfunction was unknown. His liver biopsy tissue showed significant bile plugs in the expanded bile ducts. Notably, progression of hepatic fibrosis was demonstrated in comparison with the liver tissue obtained 1 year and 5 months ago. We recognized that he had had skin sunlight hypersensitivity from early childhood by focused history taking. Then we examined protoporphyrin in his red blood cells and conducted genetic test, and diagnosed him as erythropoietic protoporphyria (EPP). In spite of the risk of development to liver cirrhosis, there is no curative therapy for EPP at this time and it was thought that thorough shading is necessary. This EPP case is considered valuable because the serial changes in the liver tissue were observed.&lt;/p&gt;

  42. Efficacy and safety of percutaneous aspiration-sclerotherapy for symptomatic hepatic cysts

    Takayuki Kogure, Jun Inoue, Eiji Kakazu, Masashi Ninomiya, Teruyuki Umetsul, Satoshi Takai, Takuya Nakamura, Tooru Shimosegawa

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY　31　428-429　2016/11

    ISSN： 0815-9319

    eISSN： 1440-1746

  43. Profiling of hepatic portal blood metabolites in non-alcoholic fatty liver disease mice by capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS)

    Eiji Kakazu, Harmeet Malhi, Jun Inoue, Masashi Ninomiya, Takayuki Kogure, Tooru Shimosegawa

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY　31　388-388　2016/11

    ISSN： 0815-9319

    eISSN： 1440-1746

  44. Enhanced release of subgenotype B1/Bj hepatitis B virus with the core Ser21 substitutions found frequently in fulminant hepatitis patients

    Jun Inoue, Teruyuki Umetsu, Takuya Nakamura, Masashi Ninomiya, Takayuki Kogure, Eiji Kakazu, Tatsuki Morosawa, Satoshi Takai, Tooru Shimosegawa

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY　31　371-371　2016/11

    ISSN： 0815-9319

    eISSN： 1440-1746

  45. Tetraspanin CD63 mediates to the development of hepatitis B virus envelope

    Masashi Ninomiya, Eugene W. Krueger, Jing Chen, Hong Cao, Jun Inoue, Tooru Shimosegawa, Mark A. Mcniven

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY　31　354-354　2016/11

    ISSN： 0815-9319

    eISSN： 1440-1746

  46. Identification of microRNAs involved in the resistance to sorafenib in hepatocellular carcinoma

    Takayuki Kogure, Jun Inoue, Eiji Kakazu, Masashi Ninomiya, Teruyuki Umetsu, Satoshi Takai, Takuya Nakamura, Yasuteru Kondo, Tooru Shimosegawa

    HEPATOLOGY　64　268A-268A　2016/10

    ISSN： 0270-9139

    eISSN： 1527-3350

  47. The evaluation of endoplasmic reticulum (ER) stress in steatotic hepatocytes under a new 3D perfusion culture system consistent with hepatic portal blood

    Eiji Kakazu, Jun Inoue, Takayuki Kogure, Masashi Ninomiya, Tatsuki Morosawa, Teruyuki Umetsu, takuya Nakamura, Satoshi Takai, Tooru Shimosegawa

    HEPATOLOGY　64　799A-800A　2016/10

    ISSN： 0270-9139

    eISSN： 1527-3350

  48. Alteration of hepatitis B virus particle release after the manipulation of endocytosis-related proteins

    Jun Inoue, Teruyuki Umetsu, takuya Nakamura, Masashi Ninomiya, Takayuki Kogure, Eiji Kakazu, Tatsuki Morosawa, Satoshi Takai, Yasuhito Tanaka, Tooru Shimosegawa

    HEPATOLOGY　64　296A-296A　2016/10

    ISSN： 0270-9139

    eISSN： 1527-3350

  49. Host cellular tetraspanin CD63 contributes to the development of hepatitis B virus envelope

    Masashi Ninomiya, Eugene W. Krueger, Jing Chen, Hong Cao, Jun Inoue, Tooru Shimosegawa, Mark A. McNiven

    HEPATOLOGY　64　301A-301A　2016/10

    ISSN： 0270-9139

    eISSN： 1527-3350

  50. The expression of Immune-miRs could contribute to the immunopathogenesis of HCV and be modified by 1(OH) vitamin D3 supplementation

    Yasuteru Kondo, Tatsuki Morosawa, Masashi Ninomiya, Yasuyuki Fujisaka, Yasuhito Tanaka, Takayuki Kogure, Jun Inoue, Teruyuki Umetsu, Tooru Shimosegawa

    HEPATOLOGY　62　710A-710A　2015/10

    ISSN： 0270-9139

    eISSN： 1527-3350

  51. Modern Immunologyからみた肝病態 miR-139-5pは血清・肝組織毎にPBC特異的な発現パターンで病態形成に関与する

    勝見 智大, 二宮 匡史, 上野 義之

    肝臓　56　(Suppl.1)　A63-A63　2015/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

  52. AIH、PBCの病態解明と治療の新展開 miR-139-5pは肝細胞と肝内リンパ球に相反的に作用しPBC病期進行、病態形成に関与する

    勝見 智大, 二宮 匡史, 上野 義之

    日本消化器病学会雑誌　112　(臨増総会)　A145-A145　2015/03

    Publisher: (一財)日本消化器病学会

    ISSN： 0446-6586

  53. Hepatoma With HBV Replication Could Attract CX3CR1+NKG2Dlow NK Cells and CX3CR1+PD-1+CD8 T Cells

    Yasuteru Kondo, Osamu Kimura, Tomoaki Iwata, Tatsuki Morosawa, Masashi Ninomiya, Eiji Kakazu, Takayuki Kogure, Yu Nakagome, Yasuhito Tanaka, Tooru Shimosegawa

    GASTROENTEROLOGY　146　(5)　S959-S959　2014/05

    ISSN： 0016-5085

    eISSN： 1528-0012

  54. MicroRNA-133b Plays an Onco-Suppressive Role in Hepatocellular Carcinoma

    Takayuki Kogure, Yasuteru Kondo, Masashi Ninomiya, Yu Nakagome, Osamu Kimura, Tomoaki Iwata, Tatsuki Morosawa, Yasuyuki Fujisaka, Tooru Shimosegawa

    GASTROENTEROLOGY　146　(5)　S953-S953　2014/05

    ISSN： 0016-5085

    eISSN： 1528-0012

  55. 自己免疫性肝障害の病態と治療をめぐる問題点 血清内microRNAプロファイリングを用いた原発性胆汁性肝硬変の病型分類応用と病態に関与するメカニズム

    勝見 智大, 二宮 匡史, 上野 義之

    肝臓　55　(Suppl.1)　A91-A91　2014/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

  56. Down regulation of hsa-miR146b-5p might affect the immunopathogenesis of chronic hepatitis C patients

    Yasuteru Kondo, Masashi Ninomiya, Osamu Kimura, Takayuki Kogure, Yasuhito Tanaka, Yu Nakagome, Tomoaki Iwata, Tatsuki Morosawa, Yasuyuki Fujisaka, Tomoo Kobayashi, Tooru Shimosegawa

    HEPATOLOGY　60　1082A-1083A　2014

    ISSN： 0270-9139

    eISSN： 1527-3350

  57. The tricarboxylic acid (TCA) cycle of dendritic cells was disturbed by imbalance of plasma amino acid observed in cirrhosis

    Eiji Kakazu, Yasuteru Kondo, Takayuki Kogure, Masashi Ninomiya, Osamu Kimura, Tatsuki Morosawa, Tomoaki Iwata, Yoshiyuki Ueno, Tooru Shimosegawa

    HEPATOLOGY　58　973A-973A　2013/10

    ISSN： 0270-9139

    eISSN： 1527-3350

  58. The expression of miR-125b-5p is increased in serum of patients with chronic hepatitis B infection, and miR-125b-5p interferes with the detection of hepatitis B virus surface antigen

    Masashi Ninomiya, Yasuteru Kondo, Takayuki Kogure, Eiji Kakazu, Osamu Kimura, Tatsuki Morosawa, Tomoaki Iwata, Yasuyuki Fujisaka, Tooru Shimosegawa

    HEPATOLOGY　58　716A-716A　2013/10

    ISSN： 0270-9139

    eISSN： 1527-3350

  59. An appropriate amount of Sorafenib could suppress the myeloid derived suppressor cells (MDSC) and Tregs in HCC patients

    Yasuteru Kondo, Tomoaki Iwata, Osamu Kimura, Masashi Ninomiya, Tatsuki Morosawa, Eiji Kakazu, Takayuki Kogure, Tooru Shimosegawa

    HEPATOLOGY　58　823A-823A　2013/10

    ISSN： 0270-9139

    eISSN： 1527-3350

  60. PD-L1+MDSCs were induced by hepatocellular carcinoma: ex vivo and in vitro analysis

    Tomoaki Iwata, Yasuteru Kondo, Osamu Kimura, Takayuki Kogure, Eiji Kakazu, Masashi Ninomiya, Tatsuki Morosawa, Yasuyuki Fujisaka, Tooru Shimosegawa

    HEPATOLOGY　58　972A-972A　2013/10

    ISSN： 0270-9139

    eISSN： 1527-3350

  61. MicroRNA-29a regulates epithelial-mesenchymal transition via repression of E-cadherin expression by modulating CpG promoter methylation in hepatocellular carcinoma

    Takayuki Kogure, Yasuteru Kondo, Eiji Kakazu, Masashi Ninomiya, Osamu Kimura, Tomoaki Iwata, Tatsuki Morosawa, Yasuyuki Fujisaka, Tooru Shimosegawa

    HEPATOLOGY　58　411A-411A　2013/10

    ISSN： 0270-9139

    eISSN： 1527-3350

  62. A case of sarcoidosis liver caused rupture of esophageal varices due to sudden portal hypertension

    MOROSAWA Tatsuki, KONDO Yasuteru, KIMURA Osamu, IWATA Tomoaki, NINOMIYA Masashi, KAKAZU Eiji, KOGURE Takayuki, IWASAKI Takao, SHIMOSEGAWA Tooru

    Kanzo　54　(5)　354-362　2013/05/25

    Publisher: 一般社団法人 日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  63. 原発性胆汁性肝硬変における血清内microRNAの発現とバイオマーカーとしての可能性

    勝見智大, 二宮匡史, 冨田恭子, 佐藤智佳子, 石井里佳, 奥本和夫, 西瀬雄子, 渡辺久剛, 斎藤貴史, 下瀬川徹, 上野義之

    肝臓　54　(Supplement 1)　A179　2013/04/25

    ISSN： 0451-4203

  64. Detection of a new genotype 1b lymphotropic HCV strain and analysis of Th17 commitment

    Yasuteru Kondo, Masashi Ninomiya, Osamu Kimura, Eiji Kakazu, Takayuki Kogure, Tomoaki Iwata, Tatsuki Morosawa, Keigo Machida, Tooru Shimosegawa

    HEPATOLOGY　56　694A-694A　2012/10

    ISSN： 0270-9139

  65. The influence of pioglitazone on the plasma amino acids profile in patients with Nonalcoholic Steatohepatitis (NASH)

    Eiji Kakazu, Yasuteru Kondo, Takayuki Kogure, Masashi Ninomiya, Osamu Kimura, Tatsuki Morosawa, Tomoaki Iwata, Futoshi Nagasaki, Yoshiyuki Ueno, Tooru Shimosegawa

    HEPATOLOGY　56　879A-879A　2012/10

    ISSN： 0270-9139

  66. Circulating microRNAs in some patients with viral hepatitis by deep sequencing showed characteristic expression

    Masashi Ninomiya, Yasuteru Kondo, Takayuki Kogure, Eiji Kakazu, Osamu Kimura, Tatsuki Morosawa, Tomoaki Iwata, Ryo Funayama, Takeshi Nagashima, Keiko Nakayama, Yoshiyuki Ueno, Tooru Shimosegawa

    HEPATOLOGY　56　437A-437A　2012/10

    ISSN： 0270-9139

  67. Involvement of miR-29a in epigenetic regulation of E-cadherin during TGF-beta-induced epithelial-mesenchymal transition in hepatocellular carcinoma

    Takayuki Kogure, Yasuteru Kondo, Eiji Kakazu, Masashi Ninomiya, Osamu Kimura, Tomoaki Iwata, Tatsuki Morosawa, Tooru Shimosegawa

    HEPATOLOGY　56　615A-615A　2012/10

    ISSN： 0270-9139

  68. Characterization of circulating microRNAs in patients with primary biliary cirrhosis by Illumina deep sequencing

    Masashi Ninomiya, Yasuteru Kondo, Takayuki Kogure, Eiji Kakazu, Osamu Kimura, Ryo Funayama, Takeshi Nagashima, Tatsuki Morosawa, Tomoaki Iwata, Keiko Nakayama, Yoshiyuki Ueno, Tooru Shimosegawa

    HEPATOLOGY　56　1132A-1132A　2012/10

    ISSN： 0270-9139

  69. HBV-related hepatocellular carcinoma could express CX3CL1 and affect the migration of NKG2D(low)CX3CR1+NK cells

    Yasuteru Kondo, Osamu Kimura, Tomoaki Iwata, Tatsuki Morosawa, Masashi Ninomiya, Eiji Kakazu, Takayuki Kogure, Yasuhito Tanaka, Tooru Shimosegawa

    HEPATOLOGY　56　1060A-1060A　2012/10

    ISSN： 0270-9139

  70. An imbalance in plasma amino acids of advanced cirrhotic patients suppresses the maturation of dendritic cells by reducing the intracellular ATP due to interference with the mitochondrial TCA cycle

    Eiji Kakazu, Yasuteru Kondo, Takayuki Kogure, Masashi Ninomiya, Osamu Kimura, Tatsuki Morosawa, Tomoaki Iwata, Yoshiyuki Ueno, Tooru Shimosegawa

    HEPATOLOGY　56　1102A-1102A　2012/10

    ISSN： 0270-9139

  71. Pioglitazoneの非アルコール性脂肪性肝炎(NASH)に対する治療効果と血漿アミノ酸濃度に与える影響

    嘉数 英二, 近藤 泰輝, 二宮 匡史, 木村 修, 小暮 高之, 岩崎 隆雄, 長崎 太, 上野 義之, 下瀬川 徹

    肝臓　53　(Suppl.2)　A707-A707　2012/09

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  72. 肝細胞癌に対する免疫の基礎と治療への展開 HBV関連肝細胞癌より放出される液性因子は免疫細胞浸潤能、活性化に影響を与える

    近藤 泰輝, 嘉数 英二, 二宮 匡史, 木村 修, 上野 義之, 下瀬川 徹

    肝臓　53　(Suppl.1)　A86-A86　2012/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  73. 肝癌基礎 肝癌増殖における微小環境調節の新規メカニズム エキソソームを介したmicroRNAの細胞間輸送

    小暮 高之, 近藤 泰輝, 嘉数 英二, 二宮 匡史, 木村 修, 岩崎 隆雄, 上野 義之, 下瀬川 徹

    肝臓　53　(Suppl.1)　A229-A229　2012/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  74. NASH臨床 非アルコール性脂肪性肝炎(NASH)に対するpioglitazoneの治療効果と血漿アミノ酸濃度に与える影響

    嘉数 英二, 近藤 泰輝, 二宮 匡史, 木村 修, 岩崎 隆雄, 上野 義之, 下瀬川 徹

    肝臓　53　(Suppl.1)　A305-A305　2012/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  75. C型肝炎臨床 Vitamin D3製剤併用Peg-IFN/RBV治療の成績(多施設共同研究)

    近藤 泰輝, 二宮 匡史, 木村 修, 嘉数 英二, 三浦 雅人, 赤羽 武弘, 宮崎 豊, 小林 智夫, 石井 元康, 木皿 典宏, 佐々木 公美子, 中山 晴夫, 五十嵐 勇彦, 小原 範之, 上野 義之, 下瀬川 徹

    肝臓　53　(Suppl.1)　A353-A353　2012/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  76. 肝細胞癌におけるEpCAM陽性細胞の癌幹細胞の可能性と抗癌剤耐性能の解析

    木村 修, 近藤 泰輝, 二宮 匡史, 嘉数 英二, 岩崎 隆雄, 上野 義之, 下瀬川 徹

    肝臓　53　(Suppl.1)　A429-A429　2012/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  77. 次世代シークエンサーを用いたC型肝炎ウイルスのアミノ酸配列解析と従来のSanger法シークエンスとの比較

    二宮 匡史, 近藤 泰輝, 嘉数 英二, 木村 修, 上野 義之, 下瀬川 徹

    肝臓　53　(Suppl.1)　A518-A518　2012/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  78. IL28B、ITPA polymorphismとVitamin D濃度からみた肝移植後C型肝炎治療今後の可能性

    近藤 泰輝, 嘉数 英二, 二宮 匡史, 木村 修, 川岸 直樹, 上野 義之, 下瀬川 徹

    肝臓　53　(Suppl.1)　A540-A540　2012/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  79. 肝移植後C型肝炎に対する治療とIL28B、ITPA SNPの関係

    近藤 泰輝, 二宮 匡史, 上野 義之, 木村 修, 嘉数 英治, 井上 淳, 関口 悟, 川岸 直樹, 里見 進, 下瀬川 徹

    移植　46　(6)　657-657　2011/12

    Publisher: (一社)日本移植学会

    ISSN： 0578-7947

    eISSN： 2188-0034

  80. 非代償性肝硬変に出現する血漿L-Cystine/L-Glutamate不均衡はCD14+単球に酸化ストレスを与え炎症性サイトカインを増加させる

    嘉数 英二, 上野 義之, 近藤 泰輝, 井上 淳, 二宮 匡史, 木村 修, 関口 悟, 川岸 直樹, 里見 進, 下瀬川 徹

    移植　46　(6)　681-682　2011/12

    Publisher: (一社)日本移植学会

    ISSN： 0578-7947

    eISSN： 2188-0034

  81. IMMUNOLOGICAL AND VIROLOGICAL ANALYSIS OF HBV/HCV DUAL INFECTION

    Yasuteru Kondo, Yoshiyuki Ueno, Yasuhito Tanaka, Masashi Ninomiya, Eiji Kakazu, Jun Inoue, Tooru Shimosegawa

    HEPATOLOGY　54　1098A-1098A　2011/10

    ISSN： 0270-9139

  82. DEEP SEQUENCING TECHNOLOGY: HIGH FACULTY TO DIFFERENTIATE THE VIRAL VARIANTS COMPARED WITH SANGER SEQUENCING

    Masashi Ninomiya, Yoshiyuki Ueno, Yasuteru Kondo, Jun Inoue, Eiji Kakazu, Osamu Kimura, Tooru Shimosegawa

    HEPATOLOGY　54　1349A-1349A　2011/10

    ISSN： 0270-9139

  83. ASSOCIATION BETWEEN MUTATIONS IN A CYTOTOXIC T LYMPHOCYTE EPITOPE OF HEPATITIS B VIRUS AND FULMINANT HEPATITIS

    Jun Inoue, Yoshiyuki Ueno, Hirofumi Niitsuma, Yasuteru Kondo, Eiji Kakazu, Masashi Ninomiya, Osamu Kimura, Tooru Shimosegawa

    HEPATOLOGY　54　1073A-1073A　2011/10

    ISSN： 0270-9139

  84. PLASMA L-CYSTINE/L-GLUTAMATE IMBALANCE INCREASES TUMOR NECROSIS FACTOR-ALPHA FROM CIRCULATING MONOCYTES VIA SYSTEM XC-(4F2HC+XCT) IN PATIENTS WITH ADVANCED CIRRHOSIS

    Eiji Kakazu, Yoshiyuki Ueno, Yasuteru Kondo, Jun Inoue, Masashi Ninomiya, Osamu Kimura, Tooru Shimosegawa

    HEPATOLOGY　54　1104A-1104A　2011/10

    ISSN： 0270-9139

  85. 次世代シークエンサーを用いたC型肝炎ウイルスの解析

    二宮 匡史, 上野 義之, 近藤 泰輝, 井上 淳, 嘉数 英二, 岩崎 隆雄, 下瀬川 徹

    肝臓　52　(Suppl.2)　A587-A587　2011/09

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  86. 非代償性肝硬変に出現する血漿L-Cystine/L-Glutamate不均衡はCD14+単球内の還元型・酸化型グルタチオンを低下させ炎症性サイトカインを増加させる

    嘉数 英二, 上野 義之, 近藤 泰輝, 井上 淳, 二宮 匡史, 木村 修, 岩崎 隆雄, 下瀬川 徹

    肝臓　52　(Suppl.2)　A644-A644　2011/09

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  87. Vitamin DまたはDFPP併用Peg-IFN/RBV治療は免疫細胞活性化を介して抗ウイルス効果を増強する

    近藤 泰輝, 上野 義之, 涌井 祐太, 二宮 匡史, 嘉数 英二, 井上 淳, 下瀬川 徹

    肝臓　52　(Suppl.2)　A650-A650　2011/09

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  88. C型肝炎治療におけるアフェレシスの役割 DFPP併用Peg-IFN/RBV治療は免疫細胞活性化を介して抗ウイルス効果を増強する

    近藤 泰輝, 上野 義之, 二宮 匡史, 嘉数 英二, 宮崎 真理子, 伊藤 貞嘉, 下瀬川 徹

    日本アフェレシス学会雑誌　30　(Suppl.)　89-89　2011/09

    Publisher: (一社)日本アフェレシス学会

    ISSN： 1340-5888

  89. B型肝炎ウイルス遺伝子変異と病態・治療 Genotype B1/BjのHBVによる劇症肝炎とCTL epitope変異の関連

    井上 淳, 上野 義之, 涌井 祐太, 福島 耕治, 近藤 泰輝, 嘉数 英二, 二宮 匡史, 新妻 宏文, 三浦 雅人, 下瀬川 徹

    肝臓　52　(Suppl.1)　A88-A88　2011/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  90. 非代償性肝硬変に出現する血漿中L-Cystine/L-Glutamate不均衡は交換輸送体xCTを介してCD14+単球からの炎症性サイトカイン産生を増加させる

    嘉数 英二, 上野 義之, 近藤 泰輝, 福島 耕治, 井上 淳, 二宮 匡史, 涌井 祐太, 岩崎 隆雄, 下瀬川 徹

    肝臓　52　(Suppl.1)　A244-A244　2011/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  91. HBV/HCV共感染患者における免疫病態解析

    近藤 泰輝, 上野 義之, 二宮 匡史, 椎名 正明, 嘉数 英二, 井上 淳, 涌井 祐太, 福島 耕治, 下瀬川 徹

    肝臓　52　(Suppl.1)　A301-A301　2011/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  92. シトリン欠損におけるAMPKシグナルと酸化ストレス

    福島 耕治, 上野 義之, 大浦 敏博, 近藤 泰輝, 井上 淳, 嘉数 英二, 二宮 匡史, 涌井 祐太, 下瀬川 徹

    肝臓　52　(Suppl.1)　A429-A429　2011/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  93. B型C型肝炎ウイルス共感染症例における免疫学的検討

    近藤 泰輝, 上野 義之, 二宮 匡史, 嘉数 英二, 下瀬川 徹

    日本内科学会雑誌　100　(Suppl.)　115-115　2011/02

    Publisher: (一社)日本内科学会

    ISSN： 0021-5384

    eISSN： 1883-2083

  94. 2型糖尿病合併・非アルコール性脂肪性肝炎(NASH)に対するpioglitazone治療の無作為化比較試験およびTransient elastgraphyによる病態の評価

    嘉数 英二, 上野 義之, 福島 耕治, 近藤 泰輝, 井上 淳, 二宮 匡史, 涌井 祐太, 岩崎 隆雄, 下瀬川 徹, 長崎 太

    日本内科学会雑誌　100　(Suppl.)　115-115　2011/02

    Publisher: (一社)日本内科学会

    ISSN： 0021-5384

    eISSN： 1883-2083

  95. 【自己免疫性胆管疾患のオーバーラップス PBC/AIH、PSC/AIHとPSC/IgG4関連硬化性胆管炎を中心に】 PBCとその類縁疾患、オーバーラップス 基礎 ウイルス感染とPBC

    二宮匡史, 福島耕治, 上野義之, 下瀬川徹

    肝・胆・膵　62　(4)　665-669　2011

  96. AMPK SIGNALS AND HEPATIC PATHOPHYSIOLOGY OF ADULT CITRULLINEMIA TYPE 2

    Koji Fukushima, Yoshiyuki Ueno, Toshihiro Ohura, Jun Inoue, Yasuteru Kondo, Eiji Kakazu, Masashi Ninomiya, Yuta Wakui, Tooru Shimosegawa

    HEPATOLOGY　52　(4)　1034A-1035A　2010/10

    ISSN： 0270-9139

  97. THE SIGNIFICANCE OF FRAMESHIFT IN THE PRECORE REGION OF HEPATITIS B VIRUS OBTAINED FROM FULMINANT HEPATITIS PATIENTS

    Jun Inoue, Yoshiyuki Ueno, Yuta Wakui, Koji Fukushima, Yasuteru Kondo, Eiji Kakazu, Masashi Ninomiya, Hirofumi Niitsuma, Tooru Shimosegawa

    HEPATOLOGY　52　(4)　990A-991A　2010/10

    ISSN： 0270-9139

  98. ANALYSIS OF CHEMOKINES DERIVED FROM HBV-REPLICATED HEPATOCELLULAR CARCINOMA AND INFRAMED HEPATOCYTE

    Yasuteru Kondo, Yoshiyuki Ueno, Koju Kobayashi, Masashi Ninomiya, Jun Inoue, Yuta Wakui, Eiji Kakazu, Koji Fukushima, Yasuhito Tanaka, Tooru Shimosegawa

    HEPATOLOGY　52　(4)　1006A-1007A　2010/10

    ISSN： 0270-9139

  99. INHIBITORY EFFECT ON HEPATITIS B VIRUS IN VITRO BY A PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-GAMMA LIGAND, ROSIGLITAZONE

    Yuta Wakui, Jun Inoue, Yoshiyuki Ueno, Koji Fukushima, Yasuteru Kondo, Eiji Kakazu, Masashi Ninomiya, Tooru Shimosegawa

    HEPATOLOGY　52　(4)　991A-991A　2010/10

    ISSN： 0270-9139

  100. HBs抗体陽性レシピエントに骨髄移植を施行しエンテカビル中止後にHBV再活性化が認められたde novo B型肝炎の一例

    涌井 祐太, 井上 淳, 上野 義之, 二宮 匡史, 嘉数 英二, 近藤 泰輝, 福島 耕治, 下瀬川 徹

    肝臓　51　(Suppl.3)　A749-A749　2010/10

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  101. 2型糖尿病合併・非アルコール性脂肪性肝炎(NASH)に対するpioglitazone治療の無作為化比較試験およびTransient elastgraphyによる病態の評価

    嘉数 英二, 上野 義之, 福島 耕治, 近藤 泰輝, 井上 淳, 二宮 匡史, 涌井 祐太, 岩崎 隆雄, 下瀬川 徹

    肝臓　51　(Suppl.2)　A609-A609　2010/09

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  102. L-cystineはLPS刺激時の単球からのTNF-α産生を高め、非代償性肝硬変の腎機能低下に関与する

    嘉数 英二, 上野 義之, 近藤 泰輝, 福島 耕治, 井上 淳, 二宮 匡史, 涌井 祐太, 下瀬川 徹

    肝臓　51　(Suppl.2)　A611-A611　2010/09

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  103. STRESS-RELATED PROTEINS DERIVED FROM HBV-INFECTED-HEPATOCYTES ENHANCE THE SECRETORY FUNCTIONS OF REGULATORY T CELLS

    Yasuteru Kondo, Yoshiyuki Ueno, Masashi Ninomiya, Yuta Wakui, Jun Inoue, Masaaki Shiina, Eiji Kakazu, Keiichi Tamai, Koju Kobayashi, Koji Fukushima, Noriyuki Obara, Tomoo Kobayashi, Motoyasu Ishii, Hirofumi Niitsuma, Yasuhito Tanaka, Tooru Shimosegawa

    HEPATOLOGY　50　(4)　972A-972A　2009/10

    ISSN： 0270-9139

  104. 非代償性肝硬変で出現する血漿アミノ酸不均衡は樹状細胞の成熟化を抑制する

    嘉数 英二, 上野 義之, 近藤 泰輝, 福島 耕治, 椎名 正明, 井上 淳, 玉井 恵一, 二宮 匡史, 下瀬川 徹

    東北医学雑誌　121　(1)　98-100　2009/06/25

    Publisher: 東北医学会

    ISSN： 0040-8700

  105. HBV感染の際に肝細胞より産生されるsHSP60のTregs活性化における意義

    近藤 泰輝, 上野 義之, 嘉数 英二, 二宮 匡史, 椎名 正明, 井上 淳, 玉井 恵一, 涌井 裕太, 小林 智夫, 石井 元康, 小林 光樹, 下瀬川 徹

    Minophagen Medical Review　54　(2)　137-139　2009/04

    Publisher: (株)ミノファーゲン製薬

    ISSN： 0388-4783

  106. 肝硬変症例に対する抗ウイルス治療を含む包括的マネージメント 分岐鎖アミノ酸(BCAA)の樹状細胞成熟化に対する影響とBCAA製剤内服後の血行動態が末梢血単核球に与える影響について

    嘉数 英二, 上野 義之, 近藤 泰輝, 福島 耕治, 山極 洋子, 椎名 正明, 井上 淳, 玉井 恵一, 二宮 匡史, 城戸 治, 中込 悠, 小原 範之, 木村 修, 涌井 祐太, 岩崎 隆雄, 下瀬川 徹

    肝臓　50　(Suppl.1)　A111-A111　2009/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  107. HBV感染肝細胞より産生されるsHSP60はTLR2を介してTregsの機能を増強する

    近藤 泰輝, 上野 義之, 小林 光樹, 椎名 正明, 嘉数 英二, 井上 淳, 玉井 恵一, 二宮 匡史, 福島 耕治, 下瀬川 徹

    肝臓　50　(Suppl.1)　A192-A192　2009/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  108. 過去10年間における宮城県のE型肝炎の発生状況

    井上 淳, 上野 義之, 長崎 太, 赤羽 武弘, 福島 耕治, 近藤 泰輝, 嘉数 英二, 玉井 恵一, 城戸 治, 中込 悠, 二宮 匡史, 小原 範之, 涌井 祐太, 岡本 宏明, 下瀬川 徹

    肝臓　50　(Suppl.1)　A218-A218　2009/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  109. HCV感染における小胞輸送タンパクHrsの役割

    玉井 恵一, 椎名 正明, 近藤 泰輝, 涌井 祐太, 城戸 治, 中込 悠, 二宮 匡史, 嘉数 英二, 井上 淳, 山極 洋子, 福島 耕治, 岩崎 隆雄, 小林 光樹, 上野 義之, 下瀬川 徹

    肝臓　50　(Suppl.1)　A232-A232　2009/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  110. ヒト末梢血単核球細胞からのhepatocyte-like cell作成についての検討

    二宮 匡史, 上野 義之, 岩崎 隆雄, 福島 耕治, 近藤 泰輝, 井上 淳, 嘉数 英二, 玉井 恵一, 城戸 治, 中込 悠, 小原 範之, 涌井 祐太, 下瀬川 徹

    肝臓　50　(Suppl.1)　A340-A340　2009/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  111. RosiglitazoneはHepG2細胞においてHBVの増殖を抑制する

    涌井 祐太, 井上 淳, 上野 義之, 小原 範之, 城戸 治, 二宮 匡史, 中込 悠, 玉井 恵一, 嘉数 英二, 近藤 泰輝, 椎名 正明, 福島 耕治, 下瀬川 徹

    肝臓　50　(Suppl.1)　A376-A376　2009/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  112. HEPATITIS B VIRUS-REPLICATION COULD INDUCE SHSP60 AND ENHANCE REGULATORY T CELL ACTIVITY VIA TOLL LIKE RECEPTOR 2

    Yasuteru Kondo, Yoshiyuki Ueno, Satanori Kon, Jun Inoue, Masashi Ninomiya, Eiji Kakazu, Masaaki Shiina, Keiichi Tamai, Yuta Wakui, Koju Kobayashi, Koji Fukushima, Takayuki Kogure, Hirofumi Niitsuma, Yasuhito Tanaka, Masashi Mizokami, Tooru Shimosegawa

    HEPATOLOGY　48　(4)　678A-679A　2008/10

    ISSN： 0270-9139

  113. LYMPHOTROPIC HCV STRAIN CAN REPLICATE IN PRIMARY NAIVE CD4(+) CELLS AND SUPPRESS THE DEVELOPMENT AND PROLIFERATION ACTIVITY

    Yasuteru Kondo, Yoshiyuki Ueno, Koju Kobayashi, Eiji Kokazu, Keigo Machida, Satonori Kon, Masaaki Shiina, Keiichi Tamai, Jun Inoue, Masashi Ninomiya, Yuta Wakui, Koji Fukushima, Takayuki Kogure, Michael M. Lai, Tooru Shimosegawa

    HEPATOLOGY　48　(4)　784A-784A　2008/10

    ISSN： 0270-9139

  114. 免疫賦活検証における培養HCV系の有用性

    椎名 正明, 小林 光樹, 近藤 泰輝, 涌井 祐太, 小原 範之, 中込 悠, 城戸 治, 二宮 匡史, 嘉数 英二, 井上 淳, 小暮 高之, 山極 洋子, 福島 耕治, 新妻 宏文, 岩崎 隆雄, 上野 義之, 下瀬川 徹

    肝臓　49　(Suppl.2)　A536-A536　2008/09

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  115. 肝炎ウイルス感染・複製・排除のメカニズム 劇症肝炎患者から得られたHBV株の持つ細胞障害性についての検討

    井上 淳, 上野 義之, 長崎 太, 新妻 宏文, 涌井 祐太, 小原 範之, 木村 修, 城戸 治, 中込 悠, 二宮 匡史, 嘉数 英二, 松田 泰徳, 近藤 泰輝, 小暮 高之, 山極 洋子, 福島 耕治, 下瀬川 徹

    肝臓　49　(Suppl.1)　A66-A66　2008/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  116. リンパ指向性HCVの液性免疫及び細胞性免疫に与える影響

    近藤 泰輝, 上野 義之, 小林 光樹, 嘉数 英二, 椎名 正明, 二宮 匡史, 涌井 佑太, 福島 耕治, 小暮 高之, 井上 淳, 木村 修, 城戸 治, 中込 悠, 小原 範之, 下瀬川 徹

    肝臓　49　(Suppl.1)　A138-A138　2008/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  117. 肝細胞癌におけるABCG2の発現とcancer stem cellの可能性

    木村 修, 小暮 高之, 上野 義之, 福島 耕治, 長崎 太, 近藤 泰輝, 井上 淳, 嘉数 英二, 松田 泰徳, 城戸 治, 中込 悠, 二宮 匡史, 小原 範之, 涌井 祐太, 岩崎 隆雄, 下瀬川 徹

    肝臓　49　(Suppl.1)　A148-A148　2008/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  118. 非代償性肝硬変のアミノ酸imbalanceはBDCA1+circulating dendritic cellの成熟化を抑制する

    嘉数 英二, 上野 義之, 福島 耕治, 山極 洋子, 長崎 太, 小暮 高之, 近藤 泰輝, 井上 淳, 松田 泰徳, 二宮 匡史, 中込 悠, 城戸 治, 木村 修, 小原 範之, 涌井 祐太, 菅野 記豊, 下瀬川 徹

    肝臓　49　(Suppl.1)　A154-A154　2008/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  119. Kupffer細胞に対する遊離脂肪酸の生理学的作用

    小原 範之, 福島 耕治, 上野 義之, 涌井 祐太, 木村 修, 中込 悠, 二宮 匡史, 城戸 治, 嘉数 英二, 松田 泰徳, 近藤 泰輝, 井上 淳, 小暮 高之, 長崎 太, 山極 洋子, 下瀬川 徹

    肝臓　49　(Suppl.1)　A377-A377　2008/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

  120. Analysis of the entire genomes of fifteen torque teno midi virus variants classifiable into a third group of genus Anellovirus.

    Ninomiya M, Takahashi M, Shimosegawa T, Okamoto H

    Arch Virol　152　(11)　1961-1975　2007

    DOI： 10.1007/s00705-007-1046-6 　

  121. わが国のE型肝炎の疫学的動向 当科における急性E型肝炎症例の臨床像の検討

    長崎 太, 上野 義之, 赤羽 武弘, 二宮 匡史, 中込 悠, 城戸 治, 松田 泰徳, 嘉数 英二, 井上 淳, 小暮 高之, 山極 洋子, 福島 耕治, 新妻 宏文, 岡本 宏明, 下瀬川 徹

    肝臓　47　(Suppl.3)　539-539　2006/11

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

  122. 分岐鎖アミノ酸(BCAA)の単球由来樹状細胞に与える影響について

    嘉数 英二, 菅野 記豊, 上野 義之, 二宮 匡史, 福島 耕治, 山極 洋子, 長崎 太, 小暮 高之, 松田 泰徳, 中込 悠, 城戸 治, 岩崎 隆雄, 下瀬川 徹

    肝臓　47　(Suppl.1)　A140-A140　2006/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

  123. 肝細胞癌におけるGalectin-3の発現の検討

    松田 泰徳, 山極 洋子, 上野 義之, 中込 悠, 二宮 匡史, 城戸 治, 嘉数 英二, 玉井 恵一, 井上 淳, 近藤 泰輝, 守時 由起, 小暮 高之, 長崎 太, 福島 耕治, 新妻 宏文, 岩崎 隆雄, 下瀬川 徹

    肝臓　47　(Suppl.1)　A89-A89　2006/04

    Publisher: (一社)日本肝臓学会

    ISSN： 0451-4203

    eISSN： 1881-3593

Show all ︎Show first 5

Research Projects 4

  1. ミトコンドリアを介する自然免疫応答を標的としたB型肝炎ウイルスの制御と肝発癌抑制

    井上 淳, 二宮 匡史, 佐野 晃俊

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(C)

    Institution: 東北大学

    2023/04/01 - 2026/03/31

  2. 肝細胞脂肪変性における遊離アミノ酸の細胞内ストレス応答機構に与えるインパクト

    嘉数 英二, 濱田 晋, 岩田 朋晃, 井上 淳, 小暮 高之, 二宮 匡史

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(C)

    Institution: 東北大学

    2020/04/01 - 2023/03/31

    More details Close

    飽食の時代背景を基に全世界で肥満・糖尿病が増加しており、それに伴い非アルコール性脂肪性肝疾患（NAFLD）も急増している。約25%のNAFLDは非アルコール性脂肪性肝炎（NASH）に進行することが知られ、2018年日本肝臓学会の 肝硬変実態調査により我が国のNASHによる肝硬変・肝癌の急速な増加が明らかとなった。現在、NASHに対する治療は食事・運動療法が中心で治療薬がなく、病態解明・バイオマーカーの同定・治療薬開発は急務である。NASHの発症機序は不明であるが、様々な環境因子・遺伝因子によりこれらの病態が惹起されると考えられている。 過栄養状態でも飢餓状態でも脂肪肝は起こるため、食事から吸収される栄養素・代謝産物の解析はNAFLD/NASHの環境因子解明に極めて重要である。門脈血由来の過剰なTGや脂肪酸は肝細胞内に脂肪滴として蓄えられる。脂質に関しても飽和脂肪酸のパルミチン酸は細胞内でTGとなるだけでなく脂肪毒性（lipotoxicity）をもち、NASH発症の主な環境要因と考えられている。過剰な糖質・脂質の肝細胞脂肪化への関与は明らかだが、遊離アミノ酸の関与はこれまであまり知られていない。脂肪滴の一部はVLDLとして血中に放出されるが、飢餓状態 ではタンパク質（アミノ酸）欠乏によりアポ蛋白によるVLDLの放出が障害されると考えられている。また、Metとコリンを欠損させた食餌（MCD diet）がマウスに肝細胞脂肪化と炎症細胞浸潤をきたすことが知られている。しかしこれらの現象に対する遊離アミノ酸の作用メカニズムは明らかではない。本研究では門脈血中遊離アミノ酸の不均衡と脂肪肝の発症メカニズムを明らかにすることを目的とした。

  3. Mechanistic analysis of hepatitis B virus infection focusing on vesicle trafficking system and its clinical application

    Inoue Jun

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    2019/04/01 - 2022/03/31

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    We analyzed effects of hepatitis B virus (HBV) infection on the intracellular vesicle trafficking system, focusing on Rab proteins. We have shown that Rab5B inhibited the release of HBV particles from hepatocytes previously. In this study, we showed that HBV infection downregulated Rab5B expression using clinical samples from patients with acute infection and cultured cells. This downregulation was considered to increase HBV release. In contrast, Rab5B expression was increased during chronic infection of HBV and, there was a significant association between Rab5B mRNA and serum HBV DNA, suggesting a possible link between the pathogenesis of chronic hepatitis B and changes of vesicle trafficking system through different mechanisms. In addition, it was revealed that CD63, one of exosome markers, is required for the efficient formation of HBV envelope.

  4. The possibility of unknown viral infection with primary biliary cirrhosis and the disease association with anellovirus infection.

    NINOMIYA Masashi

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Young Scientists (B)

    Institution: Tohoku University

    2011 - 2012

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    We tried to sequence hepatitis C virus (HCV) genome with RDV method, before conducting RDV method with serum in PBC patients or NOD. c3c4 mice. But this method seemed to be impossible to detect unknown viral sequence. Therefore, we tried to use deep sequencing technology. Result: The reads of HCV origin mapped 8583 reads on the reference HCV genome. The reads of HCV origin were detectable in about 0.10% of the total reads. Surprisingly, the coverage showed 98.8% and read depth indicated 69.5x. In NS3, the position of 5 amino acid bases showed mixed variants.