研究者詳細 - 寺井　崇二

論文 - 寺井　崇二

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Edwardsiella tardaによる大量膿瘍をきたした肝硬変患者の1例症例報告(Massive empyema with Edwardsiella tarda in a patient with liver cirrhosis: a case report)

水戸將貴, 木村成宏, 山崎華子, 神保遼, 小島雄一, 荒生祥尚, 林和直, 土屋淳紀, 寺井崇二

日本消化器病学会甲信越支部例会・日本消化器内視鏡学会甲信越支部例会抄録集 71回・93回 47 - 47 2022年12月

HBx and YAP expression could promote tumor development and progression in HBV-related hepatocellular carcinoma. 国際誌

Chiyumi Oda, Kenya Kamimura, Osamu Shibata, Shinichi Morita, Yuto Tanaka, Toru Setsu, Hiroyuki Abe, Takeshi Yokoo, Akira Sakamaki, Hiroteru Kamimura, Satoshi Kofuji, Toshifumi Wakai, Hiroshi Nishina, Shuji Terai

Biochemistry and biophysics reports 32 101352 - 101352 2022年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

Background: Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) accounts for 10%-20% of the total HCC numbers. Its clinical features include the occurrence in the younger generation, large tumors, and poor prognosis. The contribution of hepatitis B virus X (HBx) protein in hepatocytes during activation of various oncogenic pathways has been reported. We aimed to assess the possible association between HBx and Yes-associated protein (YAP) expression in the liver tissue and the clinical features of HBV-related HCC. Methods: The relationship between HBx and YAP expression was examined in vivo using HCC tumor and peritumor tissues (n = 55). The clinical information including tumor size, marker, and the prognosis was assessed with protein expressions. The in vitro gene expression analyses were conducted using HBx- and YAP-overexpressing HCC cell lines. Results: Among 19 cases of HBV-related, 17 cases of hepatitis C virus (HCV)-related, and 19 cases of nonviral-related HCC, the HBV-related tumor showed the largest size. The HBx-stained area in the tumor and peritumor tissue showed a significant correlation with tumor size and serum α-fetoprotein level. YAP expression was higher in HBV-related tumor tissue than in the peritumor tissue and HCV-related tumor. Additionally, HBx and YAP protein expressions are correlated and both expressions in the tumor contributed to the poor prognosis. An in vitro study demonstrated that HBx and YAP overexpression in the hepatocytes activate the various oncogenic signaling pathways. Conclusions: Our study demonstrated that YAP expression in the liver of HBV-infected patients might be the key factor in HBV-related HCC development and control of tumor-related features.

DOI： 10.1016/j.bbrep.2022.101352

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Gene panel testing detects important genetic alterations in ulcerative colitis-associated colorectal neoplasia. 国際誌

Yoshifumi Shimada, Mae Nakano, Ken-Ichi Mizuno, Junji Yokoyama, Akio Matsumoto, Kana Tanaka, Hidehito Oyanagi, Masato Nakano, Yuki Hirose, Hiroshi Ichikawa, Jun Sakata, Hitoshi Kameyama, Yasumasa Takii, Mika Sugai, Yiwei Ling, Shiho Takeuchi, Shujiro Okuda, Shuji Terai, Yoichi Ajioka, Toshifumi Wakai

Oncology letters 24 ( 6 ) 442 - 442 2022年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

Ulcerative colitis-associated neoplasia (UCAN) harbors unique genetic alterations and mutational tendencies. The clinical application of gene panel testing enables precision medicine by tailoring treatment to individual gene alterations. We hypothesized that gene panel testing may detect clinically important genetic alterations in UCAN, with potential usefulness for the diagnosis and treatment of UCAN. In the present study, gene panel testing was used to identify genetic alterations in UCAN, and the possibility of clinical utility of gene panel testing in UCAN was investigated. The present study included 15 patients with UCAN, and gene panel testing was performed to identify genetic alterations associated with diagnosis and treatment. Genetic alterations of UCAN were compared with those of 203 patients with sporadic colorectal cancer (CRC). APC and PTEN mutations were less frequent, while RNF43 frameshift or nonsense mutations were more frequent in UCAN compared with sporadic CRC. TP53 mutations were identified in 13/15 patients (87%) with UCAN. Notably, 4/15 patients (27%) with UCAN had no genetic alterations other than TP53 mutation, while this occurred in 1/203 patients (0.5%) with sporadic CRC (P<0.001). Microsatellite instability-high was identified in 2/15 patients (13%) with UCAN. Mutational signature 3, which is associated with homologous recombination deficiency, was detected in 14/15 patients (93%) with UCAN, and enriched in UCAN compared with sporadic CRC (P=0.030). In conclusion, gene panel testing can detect important genetic alterations that can be useful for diagnosis and treatment in UCAN, and may provide clinicians with important information for tailored treatment strategies.

DOI： 10.3892/ol.2022.13562

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術後再建腸管例の悪性胆道狭窄に対するバルーン内視鏡下胆道ドレナージの有用性

名古屋拓郎, 寺井崇二, 林和直, 五十嵐聡, 小川光平

ENDOSCOPIC FORUM for digestive disease 38 ( 2 ) 153 - 153 2022年12月

糖鎖欠損トランスフェリン値はγ-GTP値と相補的にアルコール性肝硬変の予後不良に関連する

坂牧僚, 小山究太郎, 酒井規裕, 阿部寛幸, 上村顕也, 寺井崇二

アルコールと医学生物学 41 71 - 73 2022年12月

記述言語：日本語出版者・発行元：梵天書房

アルコール性肝硬変症例67例(男性86.6%:年齢中央値65歳)を対象に、糖鎖欠損トランスフェリン(CDT)値とγ-GTP値と予後の関連について後方視的に検討した。経過観察期間は3年とした。Cox回帰分析の結果、%CDT値は単変量で有意な予後不良因子であったが多変量では抽出されず、γ-GTP高値が独立した予後不良因子であることが分かった。対象を%CDT値およびγ-GTP値ともに正常値であった12例(1群)、一方が高値であった34例(2群)、両方とも高値であった21例(3群)に分けて予後比較した。その結果、3年生存率は1群が100.0%で有意に予後良好であった。以上より、%CDTかγ-GTPの一方が高値であると予後不良に関連することが示された。

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Two rare pancreatic parenchymal hemorrhagic lesions associated with acute pancreatitis in acute liver failure: a case report and literature review.

Ryo Jimbo, Yoshihisa Arao, Atsunori Tsuchiya, Hanako Yamazaki, Masaki Mito, Yuichi Kojima, Yuji Kobayashi, Naruhiro Kimura, Kazunao Hayashi, Shuji Terai

Clinical journal of gastroenterology 2022年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

Acute pancreatitis is an uncommon occurrence in acute liver failure. Furthermore, such cases are rarely complicated by parenchymal hemorrhages. Herein, we report the case of a 69-year-old male patient with multiple pancreatic parenchymal hemorrhages concomitant with acute liver failure. The patient underwent conservative treatment for acute liver failure caused by hepatitis B virus infection. Plain computed tomography on the 30th day revealed two high-density mass lesions in the pancreatic body and tail, which were suspected to be multiple pancreatic parenchymal hemorrhages. Despite restarting gabexate mesylate, the patient died of multiple organ failure on the 49th day. The clinical information of the present case and our literature review of 61 similar cases in 43 case reports identified via a systematic keyword search of the PubMed database, which described acute pancreatitis concomitant with acute hepatitis and acute liver failure, will aid physicians in the diagnosis and treatment of this rare condition.

DOI： 10.1007/s12328-022-01738-x

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Cell-free and concentrated ascites reinfusion therapy versus large-volume paracentesis for the treatment of cirrhotic patients with refractory ascites: A multicenter prospective observational study. 国際誌

Tatsunori Hanai, Hideto Kawaratani, Junji Nagano, Hirokazu Suii, Akira Sakamaki, Yoshitaka Arase, Hiroyuki Nakanishi, Tomomi Kogiso, Tomomi Okubo, Takao Miwa, Shogo Shimizu, Shuhei Hige, Masanori Atsukawa, Masahito Shimizu, Masayuki Kurosaki, Shuji Terai, Tatehiro Kagawa, Katsutoshi Tokushige, Hitoshi Yoshiji

Hepatology research : the official journal of the Japan Society of Hepatology 53 ( 3 ) 238 - 246 2022年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

AIM: Cell-free and concentrated ascites reinfusion therapy (CART) and large-volume paracentesis (LVP) with albumin infusion are useful for managing refractory ascites (RA). However, it remains unclear which therapy is more effective in patients with cirrhosis with RA. METHODS: From June 2018 to March 2022, 25 patients with RA treated with CART or LVP with albumin infusion were enrolled in this multicenter prospective observational study to investigate the number of abdominal paracenteses, albumin preparations used, and drainage volume during an 8-week observation period. RESULTS: Among all patients at entry (median age, 63 years; 52% men; 60% Child-Pugh B and 40% Child-Pugh C), 92% were treated with furosemide (median, 20 mg/day), 92% with spironolactone (25 mg/day), and all with tolvaptan (7.5 mg/day). Patients with RA had a poor health-related quality of life (HRQOL) and prominent ascites-related symptoms. Four of the 20 eligible patients were treated with CART, 11 with LVP with albumin infusion, and five with their combination. The median number of paracenteses, total drainage volume, and albumin infusions were 1.5, 7.4 L, and 0, respectively, in the CART group; 5.0, 22.0 L, and 5.0, respectively, in the LVP group; and 5.0, 30.0 L, and 5.0, respectively in their combination group. The treatment effects did not differ significantly among the three groups regarding weight loss, liver function, renal function, electrolytes, and HRQOL. However, patients treated with CART had fewer paracenteses and albumin infusions than those treated with LVP. CONCLUSIONS: CART and LVP have comparable therapeutic efficacy for RA in patients with cirrhosis.

DOI： 10.1111/hepr.13860

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Weakly Supervised Multiple Instance Learning for Liver Cirrhosis Classification using Ultrasound Images

Yusuke Fujita, Kaito Ishihara, Kazuma Nakata, Yoshihiko Hamamoto, Makoto Segawa, Isao Sakaida, Yoshihiro Mitani, Shuji Terai

2022 7th International Conference on Intelligent Informatics and Biomedical Science (ICIIBMS) 2022年11月

Early‐phase prothrombin time‐international normalized ratio in acute liver injury indicates the timing of therapeutic intervention and predicts prognostic improvement

Kotaro Kumagai, Seiichi Mawatari, Akihiro Moriuchi, Kohei Oda, Yasuhiro Takikawa, Naoya Kato, Shigeto Oda, Kazuaki Inoue, Shuji Terai, Takuya Genda, Masahito Shimizu, Isao Sakaida, Satoshi Mochida, Akio Ido

Hepatology Research 53 ( 2 ) 160 - 171 2022年11月

【再生医療の現状と展望】間葉系幹細胞を用いた肝疾患の再生医療

土屋淳紀, 寺井崇二

BIO Clinica 37 ( 12 ) 1089 - 1093 2022年11月

記述言語：日本語出版者・発行元：(株)北隆館

肝硬変に対しては,本来自らが持つ線維化改善能力を促進させる薬剤の開発が行われている。間葉系幹細胞もその中で注目されているものの一つで生体内で"指揮細胞"として働き,肝内の"実働細胞"であるマクロファージに影響し,マクロファージを抗炎症性に変化させ肝硬変の改善に影響を及ぼすことを明らかにしてきた。更に,間葉系幹細胞のエクソソームは非常に重要で特にIFNγで間葉系幹細胞を刺激後に得られるエクソソームは肝硬変マウスに高い治療効果を発揮した。今後間葉系幹細胞,そしてそのエクソソームを用いた治療は高い治療効果を求めて次のステージへと動き始めている。(著者抄録)

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小児NAFLD患者の背景疾患と移行医療への課題

上村博輝, 佐藤毅昂, 山崎文紗子, 坂牧僚, 土屋淳紀, 寺井崇二, 長崎啓祐, 齋藤昭彦

肥満研究 28 ( Suppl. ) 290 - 290 2022年11月

小児NAFLD患者の背景疾患と移行医療への課題

上村博輝, 佐藤毅昂, 山崎文紗子, 坂牧僚, 土屋淳紀, 寺井崇二, 長崎啓祐, 齋藤昭彦

肥満研究 28 ( Suppl. ) 290 - 290 2022年11月

Letrozole ameliorates liver fibrosis through the inhibition of the CTGF pathway and 17β-hydroxysteroid dehydrogenase 13 expression.

Norihiro Sakai, Kenya Kamimura, Hirotaka Miyamoto, Masayoshi Ko, Takuro Nagoya, Toru Setsu, Akira Sakamaki, Takeshi Yokoo, Hiroteru Kamimura, Hiroyuki Soki, Ayako Tokunaga, Tatsuo Inamine, Mikiro Nakashima, Hatsune Enomoto, Kazuki Kousaka, Hidehisa Tachiki, Kaname Ohyama, Shuji Terai

Journal of gastroenterology 58 ( 1 ) 53 - 68 2022年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: To establish a treatment option for liver fibrosis, the possibility of the drug repurposing theory was investigated, with a focus on the off-target effects of active pharmaceutical ingredients. METHODS: First, several active pharmaceutical ingredients were screened for their effects on the gene expression in the hepatocytes using chimeric mice with humanized hepatocytes. As per the gene expression-based screening assay for 36 medications, we assessed the mechanism of the antifibrotic effect of letrozole, a third-generation aromatase inhibitor, in mouse models of liver fibrosis induced by carbon tetrachloride (CCl4) and a methionine choline-deficient (MCD) diet. We assessed liver histology, serum biochemical markers, and fibrosis-related gene and protein expressions in the hepatocytes. RESULTS: A gene expression-based screening assay revealed that letrozole had a modifying effect on fibrosis-related gene expression in the hepatocytes, including YAP, CTGF, TGF-β, and CYP26A1. Letrozole was administered to mouse models of CCl4- and MCD-induced liver fibrosis and it ameliorated the liver fibrosis. The mechanisms involved the inhibition of the Yap-Ctgf profibrotic pathway following a decrease in retinoic acid levels in the hepatocytes caused by suppression of the hepatic retinol dehydrogenase, Hsd17b13 and activation of the retinoic acid hydrogenase, Cyp26a1. CONCLUSIONS: Letrozole slowed the progression of liver fibrosis by inhibiting the Yap-Ctgf pathway. The mechanisms involved the modification of the Hsd17b13 and Cyp26a1 expressions led to the suppression of retinoic acid in the hepatocytes, which contributed to the activation of Yap-Ctgf pathway. Because of its off-target effect, letrozole could be repurposed for the treatment of liver fibrosis. The third-generation aromatase inhibitor letrozole ameliorated liver fibrosis by suppressing the Yap-Ctgf pathway by partially modifying the Hsd17b13 and Cyp26a1 expressions, which reduced the retinoic acid level in the hepatocytes. The gene expression analysis using chimeric mice with humanized liver revealed that the mechanisms are letrozole specific and, therefore, may be repurposed for the treatment of liver fibrosis.

DOI： 10.1007/s00535-022-01929-w

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肝再生・移植医療への新規トランスレーショナルリサーチ肝硬変に対するHMGB1部分ペプチドを用いた基礎研究から医師主導治験実施へ

土屋淳紀, 寺井崇二

肝臓 63 ( Suppl.3 ) A710 - A710 2022年10月