研究者詳細 - 寺井　崇二

論文 - 寺井　崇二

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肝移植の現状と課題当県での肝障害症例を対象としたネットワークの運用と、アンケート調査からみた県内の肝障害診療の現状と今後の啓発の必要性

薛徹, 寺井崇二

肝臓 62 ( Suppl.1 ) A113 - A113 2021年4月

肝疾患におけるビックデータとAI(人工知能)の臨床応用ディープラーニングを活用したPBC多施設データから予測する高齢者PBCの介入の必要性の検討

上村博輝, 高村昌昭, 寺井崇二

肝臓 62 ( Suppl.1 ) A208 - A208 2021年4月

肝疾患移行期医療の現状と問題点先天性心疾患術後に肝線維化悪化に影響を及ぼす因子の解析

山崎文紗子, 上村博輝, 寺井崇二

肝臓 62 ( Suppl.1 ) A167 - A167 2021年4月

【肝類洞壁細胞研究における新知見】肝の炎症、線維化と類洞壁細胞間葉系幹細胞を用いた新規治療法の開発

渡邉雄介, 土屋淳紀, 寺井崇二

肝胆膵 82 ( 4 ) 525 - 529 2021年4月

肝癌に対する局所療法としての放射線療法の安全性と有効性の検証

山田麻理奈, 上村顕也, 柴田理, 森田真一, 寺井崇二

肝臓 62 ( Suppl.1 ) A338 - A338 2021年4月

多発肝転移、リンパ節転移を伴う直腸原発神経内分泌腫瘍に対して集学的治療が有効であった一例当院での症例群の検討と共に

小川和也, 阿部寛幸, 上村顕也, 寺井崇二

肝臓 62 ( Suppl.1 ) A266 - A266 2021年4月

肝再生の可能性と障壁 HMGB1の部分ペプチドを用いた慢性肝疾患に対するセルフリー治療の開発

土屋淳紀, 野尻俊介, 寺井崇二

肝臓 62 ( Suppl.1 ) A69 - A69 2021年4月

point shear wave elastographyを利用した肝線維化のheterogeneityの検証

横尾健, 杉田萌乃, 荒生祥尚, 薛徹, 上村博輝, 坂牧僚, 上村顕也, 土屋淳紀, 高村昌昭, 寺井崇二

超音波医学 48 ( Suppl. ) S713 - S713 2021年4月

Small extracellular vesicles derived from interferon-γ pre-conditioned mesenchymal stromal cells effectively treat liver fibrosis. 国際誌

Suguru Takeuchi, Atsunori Tsuchiya, Takahiro Iwasawa, Shunsuke Nojiri, Takayuki Watanabe, Masahiro Ogawa, Tomoaki Yoshida, Katsunori Fujiki, Yuta Koui, Taketomo Kido, Yusuke Yoshioka, Mayu Fujita, Junichi Kikuta, Tohru Itoh, Masaaki Takamura, Katsuhiko Shirahige, Masaru Ishii, Takahiro Ochiya, Atsushi Miyajima, Shuji Terai

NPJ Regenerative medicine 6 ( 1 ) 19 - 19 2021年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

Mesenchymal stromal cells (MSCs) are used for ameliorating liver fibrosis and aiding liver regeneration after cirrhosis; Here, we analyzed the therapeutic potential of small extracellular vesicles (sEVs) derived from interferon-γ (IFN-γ) pre-conditioned MSCs (γ-sEVs). γ-sEVs effectively induced anti-inflammatory macrophages with high motility and phagocytic abilities in vitro, while not preventing hepatic stellate cell (HSC; the major source of collagen fiber) activation in vitro. The proteome analysis of MSC-derived sEVs revealed anti-inflammatory macrophage inducible proteins (e.g., annexin-A1, lactotransferrin, and aminopeptidase N) upon IFN-γ stimulation. Furthermore, by enabling CX3CR1+ macrophage accumulation in the damaged area, γ-sEVs ameliorated inflammation and fibrosis in the cirrhosis mouse model more effectively than sEVs. Single cell RNA-Seq analysis revealed diverse effects, such as induction of anti-inflammatory macrophages and regulatory T cells, in the cirrhotic liver after γ-sEV administration. Overall, IFN-γ pre-conditioning altered sEVs resulted in efficient tissue repair indicating a new therapeutic strategy.

DOI： 10.1038/s41536-021-00132-4

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Modulation of serotonin in the gut-liver neural axis ameliorates the fatty and fibrotic changes in non-alcoholic fatty liver. 国際誌

Masayoshi Ko, Kenya Kamimura, Takashi Owaki, Takuro Nagoya, Norihiro Sakai, Itsuo Nagayama, Yusuke Niwa, Osamu Shibata, Chiyumi Oda, Shinichi Morita, Atsushi Kimura, Ryosuke Inoue, Toru Setsu, Akira Sakamaki, Takeshi Yokoo, Shuji Terai

Disease models & mechanisms 14 ( 3 ) 2021年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

The etiology of non-alcoholic fatty liver disease (NAFLD) consists of various factors, including neural signal pathways. However, the molecular mechanisms of the autonomic neural signals influencing NAFLD progression have not been elucidated. Therefore, we examined the involvement of the gut-liver neural axis in NAFLD development and tested the therapeutic effect of modulation of this axis in this study. To test the contribution of the gut-liver neural axis, we examined NAFLD progression with respect to body weight, hepatic steatosis, fibrosis, intestinal tight junction, microbiota and short-chain fatty acids in NAFLD models of choline-deficient defined L-amino-acid and high-fat diet-fed mice with or without blockades of autonomic nerves from the liver. Blockade of the neural signal from the liver to the gut in these NAFLD mice models ameliorated the progression of liver weight, hepatic steatosis and fibrosis by modulating serotonin expression in the small intestine. It was related to the severity of the liver pathology, the tight junction protein expression, microbiota diversity and short-chain fatty acids. These effects were reproduced by administrating serotonin antagonist, which ameliorated the NAFLD progression in the NAFLD mice models. Our study demonstrated that the gut-liver neural axis is involved in the etiologies of NAFLD progression and that serotonin expression through this signaling network is the key factor of this axis. Therefore, modulation of the gut-liver neural axis and serotonin antagonist ameliorates fatty and fibrotic changes in non-alcoholic fatty liver, and can be a potential therapeutic target of NAFLD.This article has an associated First Person interview with the first author of the paper.

DOI： 10.1242/dmm.048922

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Successful treatment of positive-sense RNA virus coinfection with autoimmune hepatitis using double filtration plasmapheresis. 国際誌

Hiroteru Kamimura, Kenya Kamimura, Atsunori Tsuchiya, Shuji Terai

BMJ case reports 14 ( 3 ) 2021年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

Double filtration plasmapheresis (DFPP) is an apheretic technique that selectively removes high molecular weight substances using a plasma component filter. DFPP has been used to treat positive-sense RNA virus infections, mainly chronic hepatitis C virus (HCV) infection, because of its ability to directly eliminate viral particles from blood plasma from 2008 to about 2015, before direct-acting antiviral agents was marketed. This effect has been termed virus removal and eradication by DFPP. HCV is a positive-sense RNA virus similar to West Nile virus, dengue virus and the SARS and Middle East respiratory syndrome coronaviruses. SARS-CoV-2 is classified same viral species. These viruses are all classified in Family Flaviviridae which are family of single-stranded plus-stranded RNA viruses. Viral particles are 40-60 nm in diameter, enveloped and spherical in shape. We present a rare case of HCV removal where an RNA virus infection that copresented with virus-associated autoimmune hepatitis was eliminated using DFPP. Our results indicate that DFPP may facilitate prompt viraemia reduction and may have novel treatment applications for SARS-CoV-2, that is, use of therapeutic plasma exchange for fulminant COVID-19.

DOI： 10.1136/bcr-2020-236984

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Adipose most abundant 2 protein is a predictive marker for cisplatin sensitivity in cancers. 国際誌

Kenya Kamimura, Takeshi Suda, Yasuo Fukuhara, Shujiro Okuda, Yu Watanabe, Takeshi Yokoo, Akihiko Osaki, Nobuo Waguri, Toru Ishikawa, Toshihiro Sato, Yutaka Aoyagi, Masaaki Takamura, Toshifumi Wakai, Shuji Terai

Scientific reports 11 ( 1 ) 6255 - 6255 2021年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

Cisplatin (CDDP) is one of the chemotherapeutic drugs being used to treat various cancers. Although effective in many cases, as high doses of CDDP cause cytotoxic effects that may worsen patients' condition, therefore, a marker of sensitivity to CDDP is necessary to enhance the safety and efficiency of CDDP administration. This study focused on adipose most abundant 2 (APM2) to examine its potential as a marker of CDDP sensitivity. The relationship of APM2 expression with the mechanisms of CDDP resistance was examined in vitro and in vivo using hepatocellular carcinoma (HCC) cells, tissues and serum of HCC patients (n = 71) treated initially with intrahepatic arterial infusion of CDDP followed by surgical resection. The predictability of serum APM2 for CDDP sensitivity was assessed in additional 54 HCC patients and 14 gastric cancer (GC) patients. APM2 expression in CDDP-resistant HCC was significantly higher both in serum and the tissue. Bioinformatic analyses and histological analyses demonstrated upregulation of ERCC6L (DNA excision repair protein ERCC6-like) by APM2, which accounts for the degree of APM2 expression. The serum APM2 level and chemosensitivity for CDDP were assessed and cut-off value of serum APM2 for predicting the sensitivity to CDDP was determined to be 18.7 µg/mL. The value was assessed in HCC (n = 54) and GC (n = 14) patients for its predictability of CDDP sensitivity, resulted in predictive value of 77.3% and 100%, respectively. Our study demonstrated that APM2 expression is related to CDDP sensitivity and serum APM2 can be an effective biomarker of HCC and GC for determining the sensitivity to CDDP.Trial registration: This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000028487).

DOI： 10.1038/s41598-021-85498-7

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Evaluation of intestinal microbiota, short-chain fatty acids, and immunoglobulin a in diversion colitis. 国際誌

Kentaro Tominaga, Atsunori Tsuchiya, Takeshi Mizusawa, Asami Matsumoto, Ayaka Minemura, Kentaro Oka, Motomichi Takahashi, Tomoaki Yosida, Yuzo Kawata, Kazuya Takahashi, Hiroki Sato, Satoshi Ikarashi, Kazunao Hayashi, Ken-Ichi Mizuno, Yosuke Tajima, Masato Nakano, Yoshifumi Shimada, Hitoshi Kameyama, Junji Yokoyama, Toshifumi Wakai, Shuji Terai

Biochemistry and biophysics reports 25 100892 - 100892 2021年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

It is reported that an increase in aerobic bacteria, a lack of short-chain fatty acids (SCFAs), and immune disorders in the diverted colon are major causes of diversion colitis. However, the precise pathogenesis of this condition remains unclear. The aim of the present study was to examine the microbiota, intestinal SCFAs, and immunoglobulin A (IgA) in the diverted colon. Eight patients underwent operative procedures for colostomies. We assessed the diverted colon using endoscopy and obtained intestinal samples from the diverted colon and oral colon in these patients. We analyzed the microbiota and SCFAs of the intestinal samples. The bacterial communities were investigated using a 16S rRNA gene sequencing method. The microbiota demonstrated a change in the proportion of some species, especially Lactobacillus, which significantly decreased in the diverted colon at the genus level. We also showed that intestinal SCFA values were significantly decreased in the diverted colon. Furthermore, intestinal IgA levels were significantly increased in the diverted colon. This study was the first to show that intestinal SCFAs were significantly decreased and intestinal IgA was significantly increased in the diverted colon. Our data suggest that SCFAs affect the microbiota and may play an immunological role in diversion colitis.

DOI： 10.1016/j.bbrep.2020.100892

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Comorbidities and healthcare costs and resource use of patients with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) in the Japan medical data vision database.

Shuji Terai, Amy Buchanan-Hughes, Alvin Ng, I-Heng Lee, Ken Hasegawa

Journal of gastroenterology 56 ( 3 ) 274 - 284 2021年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: This study examined demographics, comorbidities and healthcare resource use (HCRU) and costs among Japanese patients with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). METHODS: We conducted a repeated cross-sectional analysis of the Medical Data Vision (MDV) claims database, from January 2011 to March 2018. Demographics were described at index date and by calendar year; a "NASH" subpopulation included patients with ≥ 1 claim for NASH at any time. Prevalence of pre-specified comorbidities of interest and data-emergent top comorbidities were estimated. All-cause HCRU and costs were quantified by calendar year. Outcomes were compared between 2011 and 2017 using partially overlapping t tests. RESULTS: 58,958 patients (mean age 61.6 years; 55.5% male) were included. 1139 patients (2%) were in the NASH subpopulation. At baseline, comorbid cardiovascular disease (69.4%), diabetes (62.1%) and hyperlipidaemia (54.4%) were most prevalent; comorbidity prevalence increased with age. Mean outpatient visits decreased from 9.36 per patient in 2011 to 7.80 in 2017; mean inpatient admissions increased (both p < 0.001 for 2011 vs 2017). Mean total all-cause healthcare costs ranged from \322,206 to \340,399 per patient per year between 2011 and 2017. Although total all-cause healthcare costs did not change significantly (p = 0.552), cost burden shifted from the outpatient to inpatient setting between 2011 and 2017. All-cause healthcare resource use/costs were generally higher for the NASH subgroup compared with the overall population. CONCLUSIONS: There is a high burden of disease among Japanese NAFLD/NASH patients, including a high prevalence of comorbidities which generally increase with age. Accordingly, substantial all-cause HCRU and costs were incurred.

DOI： 10.1007/s00535-021-01759-2

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Relationship between detection of hepatitis B virus in saliva and periodontal disease in hepatitis B virus carriers in Japan. 国際誌

Hiroteru Kamimura, Jun Watanabe, Tomoyuki Sugano, Junji Kohisa, Hiroyuki Abe, Kenya Kamimura, Atsunori Tsuchiya, Masaaki Takamura, Shogo Okoshi, Yoshinari Tanabe, Ritsuo Takagi, Hirofumi Nonaka, Shuji Terai

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 27 ( 3 ) 492 - 496 2021年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

INTRODUCTION: Although hepatitis B virus infection is well-described, the additional risk posed by oral bleeding in individuals with chronic hepatitis B virus infection has not been determined. This study aimed to determine the quantity of hepatitis B virus in the saliva of carriers in Japan, as a means of understanding the potential risk for horizontal transmission. METHODS: Saliva samples from 48 confirmed hepatitis B virus carriers were included in the analysis. Hepatitis B virus concentrations and the presence of occult blood as periodontal disease were evaluated in each sample. RESULTS: Hepatitis B surface antigen was identified in 46 of the 48 samples (98%), with hepatitis B virus DNA identified in 19 of the 48 saliva samples (40%). Occult blood was detected in 32 (67%) samples with the prevalence increasing as a function of age (r = 0.413; P = 0.003). There was a significantly positive correlation between hepatitis B virus DNA levels in the serum and saliva specimens (r = 0.895; P < 0.001). CONCLUSIONS: Occult blood in saliva was detected in most participants. The detection of hepatitis B virus DNA correlated positively with hepatitis B virus in the serum and occult blood in the saliva. Therefore, improved care of periodontal disease among older people is important for preventing horizontal transmission of hepatitis B virus.

DOI： 10.1016/j.jiac.2020.10.028

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当院における肝炎医療コーディネーターの取り組み・課題と今後の展望

廣川光, 荒生祥尚, 薛徹, 寺井崇二

日本消化器病学会雑誌 118 ( 臨増総会 ) A266 - A266 2021年3月

Hepatocellular carcinoma development in diabetic patients: a nationwide survey in Japan

Ryosuke Tateishi, Takeshi Matsumura, Takeshi Okanoue, Toshihide Shima, Koji Uchino, Naoto Fujiwara, Takafumi Senokuchi, Kazuyoshi Kon, Takayoshi Sasako, Makiko Taniai, Takumi Kawaguchi, Hiroshi Inoue, Hirotaka Watada, Naoto Kubota, Hitoshi Shimano, Shuichi Kaneko, Etsuko Hashimoto, Sumio Watanabe, Goshi Shiota, Kohjiro Ueki, Kosuke Kashiwabara, Yutaka Matsuyama, Hideo Tanaka, Masato Kasuga, Eiichi Araki, Kazuhiko Koike, Yoshiyasu Karino, Shuhei Hige, Masatomo Sekiguchi, Koji Ogawa, Hideaki Miyoshi, Kyu Yong Cho, Masaru Baba, Atsushi Inoue, Kazuobu Aso, Mitsuyoshi Okada, Yasuhiro Takikawa, Kei Endo, Yasushi Ishigaki, Hirobumi Togashi, Michiaki Unno, Takanori Morikawa, Hideki Katagiri, Shojiro Sawada, Hiromasa Ohira, Atsushi Takahashi, Michio Shimabukuro, Akihiro Kudo, Naomi Tanaka, Junko Mitsuhashi, Toshifumi Tokai, Yasushi Matsuzaki, Tadashi Ikegami, Masato Imai, Kou Nishikawa, Sadao Takahashi, Sumiko Nagoshi, Kosuke Maezawa, Masafumi Matsuda, Tetsuhiro Chiba, Masayuki Yokoyama, Koutaro Yokote, Yoko Hidetaka, Mitsuhiko Moriyama, Hitomi Nakamura, Midori Fujishiro, Tadakazu Hisamatsu, Kaori Nishikawa, Toshihiko Nouchi, Yuki Sakurai, Harumi Daikoku, Michinori Murayama, Yoshinori Saigusa, Takashi Matsui, Ryosuke Tateishi, Hidenari Nagai, Takanori Mukozu, Takahisa Hirose, Masahiko Miyagi, Hiroaki Sato, Akira Mizuki, Masanori Miura, Yuzuru Sato, Rena Kaneko, Kumiko Hamano, Hiroko Kato, Kentaro Kikuchi, Yusuke Kajiyama, Makoto Chuma, Hiroko Ito, Hiroshi Yasuda, Nobuyuki Matsumoto, Yasushi Tanaka, Yoshio Nagai, Kento Imajo, Yasuo Terauchi, Yuzuru Ito, Shuji Terai, Hirohito Sone, Satoshi Matsunaga

Journal of Gastroenterology 56 ( 3 ) 261 - 273 2021年3月

門脈圧亢進症:診断と治療の最前線傍食道静脈の発達の有無を指標としたEVL/EISの選択による治療成績

薛徹, 横山純二, 寺井崇二

日本消化器病学会雑誌 118 ( 臨増総会 ) A201 - A201 2021年3月

地域病院健診時の消化器サルコペニア疾患診療の有用性

上村博輝, 小島雄一, 寺井崇二

日本消化器病学会雑誌 118 ( 臨増総会 ) A345 - A345 2021年3月

【小児期発症慢性肝疾患における移行期医療の現状と課題-小児と成人のダイアログ-】NAFLD Pediatric fatty liver disease(PeFLD)における概説と成人との比較(肝組織学的検討を含めて) 小児と成人の相違

上村博輝, 山崎文紗子, 佐藤毅昂, 薛徹, 土屋淳紀, 上村顕也, 高村昌昭, 寺井崇二, 長崎啓祐, 斎藤昭彦, 梅津哉

肝胆膵 82 ( 3 ) 425 - 440 2021年3月

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