研究者詳細 - 寺井　崇二

論文 - 寺井　崇二

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Transition of clinical and basic studies on liver cirrhosis treatment using cells to seek the best treatment. 国際誌

Shuji Terai, Atsunori Tsuchiya, Yusuke Watanabe, Suguru Takeuchi

Inflammation and regeneration 41 ( 1 ) 27 - 27 2021年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

The liver is a highly regenerative organ; however, its regeneration potential is reduced by chronic inflammation with fibrosis accumulation, leading to cirrhosis. With an aim to tackle liver cirrhosis, a life-threatening disease, trials of autologous bone marrow cell infusion (ABMi) therapy started in 2003. Clinical studies revealed that ABMi attenuated liver fibrosis and improved liver function in some patients; however, this therapy has some limitations such as the need of general anesthesia. Following ABMi therapy, studies have focused on specific cells such as mesenchymal stromal cells (MSCs) from a variety of tissues such as bone marrow, adipose tissue, and umbilical cord tissues. Particularly, studies have focused on gaining mechanistic insights into MSC distribution and effects on immune cells, especially macrophages. Several basic studies have reported the use of MSCs for liver cirrhosis models, while a number of clinical studies have used autologous and allogeneic MSCs; however, there are only a few reports on the obvious substantial effect of MSCs in clinical studies. Since then, studies have analyzed and identified the important signals or components in MSCs that regulate immune cells, such as macrophages, under cirrhotic conditions and have revealed that MSC-derived exosomes are key regulators. Researchers are still seeking the best approach and filling the gap between basic and clinical studies to treat liver cirrhosis. This paper highlights the timeline of basic and clinical studies analyzing ABMi and MSC therapies for cirrhosis and the scope for future studies and therapy.

DOI： 10.1186/s41232-021-00178-3

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Advances in the Treatment of Gastrointestinal Bleeding: Safety and Efficiency of Transnasal Endoscopy. 国際誌

Hiroyuki Abe, Kenya Kamimura, Yoshihisa Arao, Junji Kohisa, Shuji Terai

Medicines (Basel, Switzerland) 8 ( 9 ) 2021年9月

記述言語：英語

Acute upper gastrointestinal bleeding (UGIB) is a common disorder and a gastroenterological emergency. With the development of new techniques and devices, the survivability after gastrointestinal bleeding is improving. However, at the same time, we are facing the difficulty of severely complicated cases with various diseases. For example, while endoscopic examination with a normal diameter endoscope is essential for the diagnosis and treatment of UGIB, there are several cases in which it cannot be used. In these cases, transnasal endoscopy (TNE) may be a viable treatment option. This report reviews current hemostatic devices for endoscopic treatment and the safety and efficiency of using TNE in complicated cases. The latter will be demonstrated in a case report where TNE was employed in a patient with severe esophageal stenosis. This review summarizes the advances made in the devices used and will provide further ideas for the physician in terms of combining these devices and TNE.

DOI： 10.3390/medicines8090053

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【肝疾患エキスパートブック栄養管理に活かすための最新情報】(Part 1)肝硬変肝硬変に対する運動療法について

上村博輝, 寺井崇二, 眞田菜緒, 小師優子

臨床栄養 139 ( 4 ) 445 - 451 2021年9月

記述言語：日本語出版者・発行元：医歯薬出版(株)

＜Key Point＞・これまで安静が基本とされていた肝硬変患者の運動については、サルコペニア対策からも最近はレジスタンス運動を含む、積極的な運動介入が推奨される傾向にある。・患者の状態(静脈瘤、腹水、肝肺症候群、サルコペニアなどの合併)に注意しながら、運動介入程度を決定していく。・"FITT"を構築して行うことが基本となるが、個人の状況に応じた継続可能な日常活動を、医師の外来診療、管理栄養士の栄養指導の際に医療機関側からアドバイスして背中を押してあげることも重要になってくる。(著者抄録)

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急性肝障害からの回復の予測バイオマーカーとしての血中セロトニン測定の意義

薛徹, 上村顕也, 大脇崇史, 荒生祥尚, 横尾健, 坂牧僚, 上村博輝, 土屋淳紀, 高村昌昭, 寺井崇二

肝臓 62 ( Suppl.2 ) A536 - A536 2021年9月

消化器領域における再生医療の研究と新たな臨床応用肝硬変に対する間葉系幹細胞やそのエクソソームを用いた治療法開発を目指して

土屋淳紀, 高村昌昭, 寺井崇二

肝臓 62 ( Suppl.2 ) A533 - A533 2021年9月

肝硬変の近未来診療肝硬変の線維化改善を目指したHMGB1部分ペプチド療法の基礎検討と医師主導治験への展開

土屋淳紀, 高村昌昭, 寺井崇二

肝臓 62 ( Suppl.2 ) A511 - A511 2021年9月

【膵癌研究最前線】膵臓選択的ハイドロダイナミック遺伝子導入法

柴田理, 上村顕也, 田中裕登, 小川光平, 阿部寛幸, 五十嵐聡, 横尾健, 寺井崇二

消化器・肝臓内科 10 ( 3 ) 342 - 346 2021年9月

The prognosis and incidence of hepatic encephalopathy of patients with liver cirrhosis treated with proton pump inhibitors: A multicenter retrospective study in Japan. 国際誌

Akira Sakamaki, Kenya Kamimura, Takeshi Yokoo, Akihiko Osaki, Seiichi Yoshikawa, Yoshihisa Arao, Toru Setsu, Hiroteru Kamimura, Nobuo Waguri, Manabu Takeuchi, Kazuhiro Funakoshi, Shuji Terai

Medicine 100 ( 32 ) e26902 2021年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

ABSTRACT: Gastrointestinal bleeding, hepatic encephalopathy (HE), and hepatocarcinogenesis are associated with the prognosis of patients with liver cirrhosis (LC). Proton pump inhibitors (PPIs) have been used to prevent bleeding, however the effects of PPIs on overall survival have not yet been elucidated. Therefore, this multicenter retrospective study aimed to assess the effect of PPI on the prognosis and HE occurrence of the patients with liver cirrhosis in Japan.A total of 456 patients diagnosed with LC at the 4 institutes during the study period (2010-2014) were assessed. PPI-treated and non-treated patients were compared using propensity score matching analysis. Primary and secondary endpoints of the study were set as the occurrence of HE and overall survival, respectively.A comparison of all cases showed a significantly poorer hepatic reserve function in the PPI-treated patients. The propensity-score matching analysis was performed and 120 PPI-treated patients were 1:1 matched with non-treated patients. The analysis revealed a higher incidence of HE in the PPI-treated than in the non-treated patients (P = .032; hazard ratio [HR], 2.162; 95% confidence interval [CI], 1.066-4.176), but the prognosis of PPI-treated patients was no worse than that of non-treated patients (P = .676; HR, 1.101; 95% CI, 0.702-1.726).This retrospective study showed that PPI administration for the patients with liver cirrhosis may partly be related to the increased incidence of HE but not worsen the patient prognosis.

DOI： 10.1097/MD.0000000000026902

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A Rare Case of Ulcerative Colitis with Severe Pneumocystis jirovecii Pneumonia and Cytomegalovirus Colitis: A Case Report and Literature Review.

Yusuke Watanabe, Kazunao Hayashi, Shuji Terai

Internal medicine (Tokyo, Japan) 2021年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

Pneumocystis jirovecii pneumonia (PJP) and cytomegalovirus (CMV) colitis are opportunistic infections that occur during immunosuppressive treatments for ulcerative colitis (UC). The prognosis of PJP and CMV colitis is very poor. We herein report a rare case of a 74-year-old UC patient with PJP and CMV colitis that was successfully treated with intensive therapy. PJP progresses rapidly, so the timing and choice of treatment are critical. Furthermore, a literature review of similar cases suggested that prophylactic therapy for opportunistic infections might be important, especially in the elderly. This case will serve as a reference for successful treatment in future cases.

DOI： 10.2169/internalmedicine.7953-21

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Risk of delayed bleeding after hot snare polypectomy and endoscopic mucosal resection in the colorectum with continuation of anticoagulants. 国際誌

Takamasa Kobayashi, Manabu Takeuchi, Yuki Hojo, Yui Ishii, Youhei Koseki, Yoko Kobayashi, Motoi Azumi, Yuji Kobayashi, Junji Kohisa, Seiichi Yoshikawa, Shuji Terai

Journal of gastrointestinal oncology 12 ( 4 ) 1518 - 1530 2021年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

Background: Current guidelines recommend the temporary discontinuation of anticoagulants before colonoscopic polypectomy, but the effect of this practice on reducing the risk of delayed bleeding after hot snare polypectomy (HSP) and endoscopic mucosal resection (EMR) remains unclear. Our aim was to assess the impact of anticoagulants on the risk of colorectal delayed bleeding after HSP and EMR, and evaluate the necessity of drug withdrawal. Methods: We reviewed the clinical data of patients with colorectal polyps using antithrombotic drugs who underwent HSP and/or EMR between January 2016 and September 2020 at Nagaoka Red Cross Hospital. After excluding antiplatelet users, patients were classified into those who continued anticoagulants [continuation group: 50 patients (93 lesions)] and those who discontinued anticoagulants [discontinuation group: 87 patients (190 lesions)]. Results: Delayed bleeding occurred in 12 lesions, and there was no significant difference in the incidence rates between the continuation and the discontinuation groups (3.2% vs. 4.7%; P=0.756). Logistic regression analysis showed that continued use of anticoagulants was not a significant risk factor for delayed bleeding compared to anticoagulant discontinuation (odds ratio, 0.670; 95% CI, 0.177-2.537; P=0.556). There was no significant difference in the incidence rate and risk of delayed bleeding, regardless of the length of the anticoagulant withdrawal period. Conclusions: Continued use of anticoagulants, compared to their discontinuation, did not increase the risk of colorectal delayed bleeding after HSP and EMR. Our results suggest that current guideline recommendations for anticoagulant withdrawal before colonoscopic polypectomy may be reconsidered. Trial Registration: UMIN000040449.

DOI： 10.21037/jgo-21-3

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The promise of radiotherapy for hepatocellular carcinoma. 国際誌

Kenya Kamimura, Shuji Terai

Hepatology research : the official journal of the Japan Society of Hepatology 51 ( 8 ) 837 - 838 2021年8月

Pyloric-gland metaplasia may be an origin of cancer and intestinal metaplasia with possible CDX2 expression. 国際誌

Kazuyoshi Yagi, Atsunori Tsuchiya, Satoru Hashimoto, Taisuke Kato, Osamu Onodera, Shuji Terai

Gastroenterology report 9 ( 4 ) 370 - 373 2021年8月

門脈圧亢進症と臓器相関心、肝、肺、腎、脾当院における心不全に伴う肝臓への影響(Cardiac Hepatopathy)の解析

上村博輝, 寺井崇二, 猪又孝文, 三井田秀, 山崎文紗子, 柏村健, 藤木信也, 渡邊雄介, 荒生祥尚, 木村成宏, 阿部寛幸, 薛徹, 坂牧僚, 横尾健

日本門脈圧亢進症学会雑誌 27 ( 3 ) 109 - 109 2021年8月

急性膵炎後の膵仮性嚢胞門脈瘻による広範な門脈血栓症を発症した2例

木村成宏, 林和直, 土屋淳紀, 寺井崇二

日本門脈圧亢進症学会雑誌 27 ( 3 ) 147 - 147 2021年8月

BRTO中に出血を来し、NBCAによるEISを併用し治療を完遂した十二指腸静脈瘤の1例

前田悠一郎, 荒生祥尚, 小島雄一, 川田雄三, 渡邉雄介, 薛徹, 阿部寛幸, 坂牧僚, 上村博輝, 横尾健, 土屋淳紀, 上村顕也, 横山純二, 寺井崇二

日本門脈圧亢進症学会雑誌 27 ( 3 ) 134 - 134 2021年8月

門脈圧亢進症を伴う肝硬変に対する薬物療法の進歩〜QOL、予後の改善を目指して〜肝硬変に伴うサルコペニアに対する難吸収性抗菌薬の有用性についての検討

坂牧僚, 土屋淳紀, 寺井崇二

日本門脈圧亢進症学会雑誌 27 ( 3 ) 106 - 106 2021年8月

潜在性肝性脳症は水素型SIBOに関連し、その治療にはリファキシミンが有効である

坂牧僚, 横山邦彦, 高橋一也, 成瀬匠, 冨永顕太郎, 佐藤裕樹, 上村顕也, 横山純二, 寺井崇二

日本門脈圧亢進症学会雑誌 27 ( 3 ) 176 - 176 2021年8月

Suppression of Noncoding RNAs as Shared Early Genetic Events in Multistep Hepatocarcinogenesis. 国際誌

Takeshi Suda, Seiichi Yoshikawa, Tsutomu Kanefuji, Satoshi Abe, Takahiro Hoshi, Shinichi Morita, Kazuyoshi Yagi, Shuji Terai

Hepatology (Baltimore, Md.) 2021年7月

A genome-wide association study identifying SVEP1 variant as a predictor of response to tolvaptan for cirrhotic ascites. 国際誌

Hideto Kawaratani, Hiromi Sawai, Masaya Onishi, Tomomi Kogiso, Noritomo Shimada, Haruki Uojima, Tomoaki Nakajima, Naoki Matsumoto, Kenichi Ikejima, Toru Ishikawa, Shuji Terai, Hiroyuki Motoyama, Atsumasa Komori, Noboru Hirashima, Satoru Saito, Yuichiro Eguchi, Masanori Nojima, Yosuke Kawai, Masakuni Tateyama, Hitoshi Yoshiji, Yasuhito Tanaka

Liver international : official journal of the International Association for the Study of the Liver 41 ( 12 ) 2944 - 2953 2021年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND & AIMS: Tolvaptan, vasopressin V2-receptor antagonist, has been used for patients with difficult-to-treat ascites in Japan. In this study, we conducted a genome-wide association study (GWAS) in the Japanese population to identify genetic variants associated with tolvaptan's efficacy for patients with hepatic ascites. METHODS: From 2014 through 2018, genomic DNA samples were obtained from 550 patients who were treated with tolvaptan. Of those, 80 cases (non-responder; increase of body weight [BW]) and 333 controls (responder; >1.5 kg decrease of BW) were included in the GWAS and replication study. RESULTS: Genome-wide association study showed 5 candidate SNPs around the miR818, KIAA1109, and SVEP1 genes. After validation and performing a replication study, an SNP (rs2991364) located in the SVEP1 gene was found to have a significant genome-wide association (OR = 3.55, P = 2.01 × 10-8 ). Multivariate analyses showed that serum sodium (Na), blood urea nitrogen (BUN) and SVEP1 SNP were significantly associated with the response (OR = 0.92, P = .003; OR = 1.02, P = .02 and OR = 3.98, P = .000008, respectively). Based on a prediction model of logistic regression analysis in a population with the rs2991364 risk allele, the failure probability (=exp (score: 22.234 + BUN*0.077 + Na*-0.179) (1 + exp (score)) was determined for the detection of non-responders. Assuming a cutoff of failure probability at 38.6%, sensitivity was 84.4%, specificity was 70% and AUC was 0.774. CONCLUSION: SVEP1 rs2991364 was identified as the specific SNP for the tolvaptan response. The prediction score (>38.6%) can identify tolvaptan non-responders and help to avoid a lengthy period of futile treatment.

DOI： 10.1111/liv.15022

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Evidence-based clinical practice guidelines for Liver Cirrhosis 2020.

Hitoshi Yoshiji, Sumiko Nagoshi, Takemi Akahane, Yoshinari Asaoka, Yoshiyuki Ueno, Koji Ogawa, Takumi Kawaguchi, Masayuki Kurosaki, Isao Sakaida, Masahito Shimizu, Makiko Taniai, Shuji Terai, Hiroki Nishikawa, Yoichi Hiasa, Hisashi Hidaka, Hiroto Miwa, Kazuaki Chayama, Nobuyuki Enomoto, Tooru Shimosegawa, Tetsuo Takehara, Kazuhiko Koike

Journal of gastroenterology 56 ( 7 ) 593 - 619 2021年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

The first edition of the clinical practice guidelines for liver cirrhosis was published in 2010, and the second edition was published in 2015 by the Japanese Society of Gastroenterology (JSGE). The revised third edition was recently published in 2020. This version has become a joint guideline by the JSGE and the Japan Society of Hepatology (JSH). In addition to the clinical questions (CQs), background questions (BQs) are new items for basic clinical knowledge, and future research questions (FRQs) are newly added clinically important items. Concerning the clinical treatment of liver cirrhosis, new findings have been reported over the past 5 years since the second edition. In this revision, we decided to match the international standards as much as possible by referring to the latest international guidelines. Newly developed agents for various complications have also made great progress. In comparison with the latest global guidelines, such as the European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases (AASLD), we are introducing data based on the evidence for clinical practice in Japan. The flowchart for nutrition therapy was reviewed to be useful for daily medical care by referring to overseas guidelines. We also explain several clinically important items that have recently received focus and were not mentioned in the last editions. This digest version describes the issues related to the management of liver cirrhosis and several complications in clinical practice. The content begins with a diagnostic algorithm, the revised flowchart for nutritional therapy, and refracted ascites, which are of great importance to patients with cirrhosis. In addition to the updated antiviral therapy for hepatitis B and C liver cirrhosis, the latest treatments for non-viral cirrhosis, such as alcoholic steatohepatitis/non-alcoholic steatohepatitis (ASH/NASH) and autoimmune-related cirrhosis, are also described. It also covers the latest evidence regarding the diagnosis and treatment of liver cirrhosis complications, namely gastrointestinal bleeding, ascites, hepatorenal syndrome and acute kidney injury, hepatic encephalopathy, portal thrombus, sarcopenia, muscle cramp, thrombocytopenia, pruritus, hepatopulmonary syndrome, portopulmonary hypertension, and vitamin D deficiency, including BQ, CQ and FRQ. Finally, this guideline covers prognosis prediction and liver transplantation, especially focusing on several new findings since the last version. Since this revision is a joint guideline by both societies, the same content is published simultaneously in the official English journal of JSGE and JSH.

DOI： 10.1007/s00535-021-01788-x

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