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3. Correction: Association of ulcerative colitis symptom severity and proctocolectomy with multidimensional patient-reported outcomes: a cross-sectional study

Author

Matsuoka, Katsuyoshi, Yamazaki, Hajime, Nagahori, Masakazu, Kobayashi, Taku, Omori, Teppei, Mikami, Yohei, Fujii, Toshimitsu, Shinzaki, Shinichiro, Saruta, Masayuki, Matsuura, Minoru, Yamamoto, Takayuki, Motoya, Satoshi, Hibi, Toshifumi, Watanabe, Mamoru, Fernandez, Jovelle, Fukuhara, Shunichi, and Hisamatsu, Tadakazu

Published
2024
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6. Association of ulcerative colitis symptom severity and proctocolectomy with multidimensional patient-reported outcomes: a cross-sectional study

Author

Matsuoka, Katsuyoshi, Yamazaki, Hajime, Nagahori, Masakazu, Kobayashi, Taku, Omori, Teppei, Mikami, Yohei, Fujii, Toshimitsu, Shinzaki, Shinichiro, Saruta, Masayuki, Matsuura, Minoru, Yamamoto, Takayuki, Motoya, Satoshi, Hibi, Toshifumi, Watanabe, Mamoru, Fernandez, Jovelle, Fukuhara, Shunichi, and Hisamatsu, Tadakazu

Published
2023
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13. AJM300 (carotegrast methyl), an oral antagonist of α4-integrin, as induction therapy for patients with moderately active ulcerative colitis: a multicentre, randomised, double-blind, placebo-controlled, phase 3 study

Author

Motoya, Satoshi, Maemoto, Atsuo, Fujiya, Mikihiro, Ashida, Toshifumi, Goto, Mitsuru, Matsumoto, Takayuki, Suzuki, Yasuo, Hamahata, Yukihiro, Nakagawa, Tomoo, Kato, Naoya, Kato, Jun, Endo, Yutaka, Suzuki, Ryoichi, Matsuda, Koichiro, Ohmiya, Naoki, Katsushima, Shinji, Hosomi, Shuhei, Tarumi, Ken-ichi, Watanabe, Chiyuki, Saito, Mitsuru, Yokoyama, Yuichiro, Inaba, Tomoki, Sakata, Yasuhisa, Hongo, Hitoshi, Shibuya, Tomoyoshi, Kawakami, Kazuhiko, Kakuta, Yoichi, Irisawa, Atsushi, Yoshimura, Naoki, Fukuda, Katsuyuki, Shirai, Takayuki, Ichikawa, Hitoshi, Nagata, Junko, Suzuki, Takayoshi, Yokoyama, Kaoru, Tomidokoro, Takashi, Kojima, Yuichiro, Yamada, Masahiro, Yamamoto, Hideko, Yamamoto, Takayuki, Horiki, Noriyuki, Obata, Hirozumi, Inoue, Satoko, Tanaka, Shinji, Toyokawa, Tatsuya, Kunihiro, Masaki, Hisabe, Takashi, Ogata, Shinichi, Takeshima, Fuminao, Matsushima, Kayoko, Matsuhashi, Nobuyuki, Sakuraba, Hirotake, Iwabuchi, Masahiro, Tsuchiya, Akihiko, Uchiyama, Kan, Kanai, Takanori, Nakamura, Masanao, Yokoyama, Tadashi, Hida, Nobuyuki, Mitsuyama, Keiichi, Osada, Taro, Hiraoka, Sakiko, Tsuzuki, Tomoyuki, Masuo, Takashige, Hokari, Ryota, Kobayashi, Taku, Saruta, Masayuki, Araki, Masao, Araki, Hiroshi, Shimizu, Masahito, Kikuchi, Masakazu, Nishikawa, Takahiro, Takedatsu, Hidetoshi, Aoyagi, Kunihiko, Ochiai, Toshiaki, Toda, Nobuo, Mizokami, Yuji, Nagahori, Masakazu, Matsueda, Kazuhiro, Kino, Hitoshi, Kanamori, Akira, Suzuki, Tsunehiro, Sakurai, Toshiharu, Kudo, Masatoshi, Kitano, Atsuo, Hisamatsu, Tadakazu, Kumagai, Shinji, Ninomiya, Tomoyuki, Mori, Kenichiro, Yoshida, Shun-ichi, Goto, Mitsuhide, Matsuoka, Katsuyoshi, Watanabe, Mamoru, Ohmori, Toshihide, Nakajima, Koichi, Ishida, Tetsuya, Ishiguro, Yoh, Kanke, Kazunari, Kobayashi, Kiyonori, Hirai, Fumihito, Watanabe, Kenji, Mizusawa, Hidehiro, Kishida, Shuji, Miura, Yoshiharu, Ohta, Akira, Kajioka, Toshifumi, and Hibi, Toshifumi

Published
2022
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20. Discontinuation of infliximab in patients with ulcerative colitis in remission (HAYABUSA): a multicentre, open-label, randomised controlled trial

Author

Kato, Shingo, Maemoto, Atsushi, Matsuura, Minoru, Sakemi, Ryosuke, Sasaki, Makoto, Tsujikawa, Tomoyuki, Esaki, Motohiro, Fukata, Norimasa, Kitamura, Kazuya, Hiraoka, Sakiko, Hokari, Ryota, Ishihara, Shunji, Mizoshita, Tsutomu, Naito, Yuji, Omata, Fumio, Saruta, Masayuki, Yoshino, Takuya, Kobayashi, Taku, Motoya, Satoshi, Nakamura, Shiro, Yamamoto, Takayuki, Nagahori, Masakazu, Tanaka, Shinji, Hisamatsu, Tadakazu, Hirai, Fumihito, Nakase, Hiroshi, Watanabe, Kenji, Matsumoto, Takayuki, Tanaka, Masanori, Abe, Takayuki, Suzuki, Yasuo, Watanabe, Mamoru, and Hibi, Toshifumi

Published
2021
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23. Adrenomedullin for steroid-resistant ulcerative colitis: a randomized, double-blind, placebo-controlled phase-2a clinical trial

Author

Kita, Toshihiro, Ashizuka, Sinya, Ohmiya, Naoki, Yamamoto, Takayuki, Kanai, Takanori, Motoya, Satoshi, Hirai, Fumihito, Nakase, Hiroshi, Moriyama, Tomohiko, Nakamura, Masanao, Suzuki, Yasuo, Kanmura, Shuji, Kobayashi, Taku, Ohi, Hidehisa, Nozaki, Ryoichi, Mitsuyama, Keiichi, Yamamoto, Shojiro, Inatsu, Haruhiko, Watanabe, Koji, Hibi, Toshifumi, and Kitamura, Kazuo

Published
2021
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24. Non-adherence to Medications in Pregnant Ulcerative Colitis Patients Contributes to Disease Flares and Adverse Pregnancy Outcomes

Author

Watanabe, Chikako, Nagahori, Masakazu, Fujii, Toshimitsu, Yokoyama, Kaoru, Yoshimura, Naoki, Kobayashi, Taku, Yamagami, Hirokazu, Kitamura, Kazuya, Takashi, Kagaya, Nakamura, Shiro, Naganuma, Makoto, Ishihara, Shunji, Esaki, Motohiro, Yonezawa, Maria, Kunisaki, Reiko, Sakuraba, Atsushi, Kuji, Naoaki, Miura, Soichiro, Hibi, Toshifumi, Suzuki, Yasuo, and Hokari, Ryota

Published
2021
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25. Recent steroid use and the relapse risk in ulcerative colitis patients with endoscopic healing.

Author

Fukuda, Tomohiro, Yamazaki, Hajime, Miyatani, Yusuke, Sawada, Tsunaki, Shibuya, Naoki, Fukuo, Yuka, Kiyohara, Hiroki, Morikubo, Hiromu, Tominaga, Keiichi, Kakimoto, Kazuki, Imai, Takayuki, Yaguchi, Katsuki, Yamamoto, Shojiro, Ando, Katsuyoshi, Nishimata, Nobuaki, Yoshihara, Takeo, Andoh, Akira, Hibi, Toshifumi, Matsuoka, Katsuyoshi, and Sugiyama, Tomoya

Subjects
ULCERATIVE colitis, STEROID drugs, ODDS ratio, LOGISTIC regression analysis
Abstract

Summary: Background: Endoscopic healing (EH) is a therapeutic target in ulcerative colitis (UC). However, even patients who have achieved EH relapse frequently. Aims: To investigate the association between recent steroid use and relapse risk in UC patients with EH. Methods: This multi‐centre cohort study included 1212 UC patients with confirmed EH (Mayo endoscopic subscore ≤1). We excluded patients with current systemic steroid use or history of advanced therapy. We divided patients into a recent steroid group (last systemic steroid use within 1 year; n = 59) and a non‐recent or steroid‐naïve group (n = 1153). We followed the patients for 2 years to evaluate relapse, defined as induction of systemic steroids or advanced therapy. We used logistic regression to estimate the odds ratio (OR) of relapse. Results: Relapse occurred in 28.8% of the recent steroid group and 5.6% of the non‐recent/steroid‐naïve group (multi‐variable‐adjusted OR 5.53 [95% CI 2.85–10.7]). The risk of relapse decreased with time since the last steroid use: 28.8% for less than 1 year after steroid therapy, 22.9% for 1 year, 16.0% for 2 years and 7.9% beyond 3 years, approaching 4.0% in steroid‐naïve patients. (ptrend <0.001). Conclusions: Even for patients with UC who achieved EH, the risk of relapse remains high following recent steroid therapy. Physicians need to consider the duration since last steroid use to stratify the relapse risk in UC patients with EH. [ABSTRACT FROM AUTHOR]

Published
2024
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26. Impact of Concomitant Thiopurine on the Efficacy and Safety of Filgotinib in Patients with Ulcerative Colitis: Post Hoc Analysis of the Phase 2b/3 SELECTION Study.

Author

Watanabe, Kenji, Peyrin-Biroulet, Laurent, Danese, Silvio, Fujitani, Yasushi, Faes, Margaux, Oortwijn, Alessandra, Lindsay, James O, Rogler, Gerhard, and Hibi, Toshifumi

Abstract

Background and Aims SELECTION is the first study to assess the impact of concomitant thiopurine and other immunomodulator [IM] use on the efficacy and safety of a Janus kinase inhibitor, filgotinib, in patients with ulcerative colitis. Methods Data from the phase 2b/3 SELECTION study were used for this post hoc analysis. Patients were randomised [2:2:1] to two induction studies [biologic-naive, biologic-experienced] to filgotinib 200 mg, 100 mg, or placebo. At Week 10, patients receiving filgotinib were re-randomised [2:1] to continue filgotinib or to switch to placebo until Week 58 [maintenance]. Outcomes were compared between subgroups with and without concomitant IM use. Results At Week 10, similar proportions of patients in the +IM and −IM groups treated with filgotinib 200 mg achieved Mayo Clinic Score [MCS] response [biologic-naive: 65.8% vs 66.9%; biologic-experienced: 61.3% vs 50.5%] and clinical remission [biologic-naive: 26.0% vs 26.2%; biologic-experienced: 11.3% vs 11.5%]. At Week 58, similar proportion of patients in the +IM and −IM groups treated with filgotinib 200 mg achieved MCS response [biologic-naive: 74.2% vs 75.0%; biologic-experienced: 45.5% vs 61.4%] and clinical remission [biologic-naive: 51.6% vs 47.4%; biologic-experienced: 22.7% vs 24.3%]. The probability of protocol-specified disease worsening during the maintenance study in patients treated with filgotinib 200 mg did not differ between +IM and −IM groups [ p  = 0.6700]. No differences were observed in the incidences of adverse events between +IM and −IM groups in the induction/maintenance studies. Conclusions The efficacy and safety profiles of filgotinib treatment in SELECTION did not differ with or without concomitant IM use. ClinicalTrials.gov identifier NCT02914522. [ABSTRACT FROM AUTHOR]

Published
2024
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29. Significance of Conducting 2 Types of Fecal Tests in Patients With Ulcerative Colitis

Author

Naganuma, Makoto, Kobayashi, Taku, Nasuno, Masanao, Motoya, Satoshi, Kato, Shingo, Matsuoka, Katsuyoshi, Hokari, Ryota, Watanabe, Chikako, Sakamoto, Hirotsugu, Yamamoto, Hironori, Sasaki, Makoto, Watanabe, Kenji, Iijima, Hideki, Endo, Yutaka, Ichikawa, Hitoshi, Ozeki, Keiji, Tanida, Satoshi, Ueno, Nobuhiro, Fujiya, Mikihiro, Sako, Minako, Takeuchi, Ken, Sugimoto, Shinya, Abe, Takayuki, Hibi, Toshifumi, Suzuki, Yasuo, and Kanai, Takanori

Published
2020
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31. A nationwide, multi-center, retrospective study of symptomatic small bowel stricture in patients with Crohn’s disease

Author

Bamba, Shigeki, Sakemi, Ryosuke, Fujii, Toshimitsu, Takeda, Teruyuki, Fujioka, Shin, Takenaka, Kento, Kitamoto, Hiroki, Umezawa, Shotaro, Sakuraba, Hirotake, Inokuchi, Toshihiro, Fukata, Norimasa, Mizuno, Shinta, Yamashita, Masaki, Shinzaki, Shinichiro, Tanaka, Hiroki, Takedatsu, Hidetoshi, Ozaki, Ryo, Moriya, Kei, Ishii, Manabu, Kinjo, Tetsu, Ozeki, Keiji, Ooi, Makoto, Hayashi, Ryohei, Kakimoto, Kazuki, Shimodate, Yuichi, Kitamura, Kazuya, Yamada, Akihiro, Sonoda, Akira, Nishida, Yu, Yoshioka, Kyouko, Ashizuka, Shinya, Takahashi, Fumiaki, Shimokawa, Toshio, Kobayashi, Taku, Andoh, Akira, and Hibi, Toshifumi

Published
2020
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33. Somatic inflammatory gene mutations in human ulcerative colitis epithelium

Author

Nanki, Kosaku, Fujii, Masayuki, Shimokawa, Mariko, Matano, Mami, Nishikori, Shingo, Date, Shoichi, Takano, Ai, Toshimitsu, Kohta, Ohta, Yuki, Takahashi, Sirirat, Sugimoto, Shinya, Ishimaru, Kazuhiro, Kawasaki, Kenta, Nagai, Yoko, Ishii, Ryota, Yoshida, Kosuke, Sasaki, Nobuo, Hibi, Toshifumi, Ishihara, Soichiro, Kanai, Takanori, and Sato, Toshiro

Published
2020
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35. Efficacy and safety of mirikizumab as induction and maintenance therapy for Japanese patients with moderately to severely active ulcerative colitis: a subgroup analysis of the global phase 3 LUCENT-1 and LUCENT-2 studies.

Author

Kobayashi, Taku, Matsuoka, Katsuyoshi, Watanabe, Mamoru, Hisamatsu, Tadakazu, Hirai, Fumihito, Milata, Joe, Li, Xingyuan, Morris, Nathan, Arora, Vipin, Ishizuka, Tomoko, Matsuo, Koji, Satoi, Yoichi, Milch, Catherine, and Hibi, Toshifumi

Subjects
ULCERATIVE colitis, CLINICAL drug trials, PLACEBOS
Abstract

Background/Aims: Mirikizumab is a p19-directed anti-interleukin-23 antibody with potential efficacy against ulcerative colitis (UC). We evaluated the efficacy and safety of mirikizumab in a Japanese subpopulation with moderately to severely active UC from the LUCENT-1 and LUCENT-2 studies. Methods: LUCENT-1 and LUCENT-2 were phase 3, randomized, double-blind, placebo-controlled trials of mirikizumab therapy in adults with moderately to severely active UC. LUCENT-1 was a 12-week induction trial where patients were randomized 3:1 to receive intravenous mirikizumab 300 mg or placebo every 4 weeks (Q4W). Patients achieving a clinical response with mirikizumab following the induction study were re-randomized 2:1 to double-blind treatment with either mirikizumab 200 mg or placebo subcutaneously Q4W during the 40-week maintenance study. The primary outcomes were clinical remission at week 12 of LUCENT-1 and week 40 of LUCENT-2. Results: A total of 137 patients enrolled in Japan were randomized to mirikizumab (n = 102) or placebo (n = 35). Compared with placebo, patients who received mirikizumab showed numerically higher clinical remission at week 12 of induction (32.4% [n = 33] vs. 2.9% [n = 1]) and at week 40 of maintenance (48.9% [n = 23] vs. 28.0% [n = 7]). A greater number of patients achieved key secondary endpoints in the mirikizumab group compared with placebo. The frequency of treatment-emergent adverse events was similar across mirikizumab and placebo groups. Efficacy and safety results observed in the Japanese subpopulation were generally consistent with those in the overall population. Conclusions: Mirikizumab induction and maintenance treatments were effective in Japanese patients with moderately to severely active UC. No new safety concerns were identified. [ABSTRACT FROM AUTHOR]

Published
2024
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36. Submucosal Injection of the RNA Oligonucleotide GUT-1 in Active Ulcerative Colitis Patients: A Randomized, Double-Blind, Placebo-Controlled Phase 2a Induction Trial.

Author

Atreya, Raja, Kühbacher, Tanja, Waldner, Maximilian J, Hirschmann, Simon, Drvarov, Oliver, Hashem, Raed Abu, Maaser, Christian, Kucharzik, Torsten, Dinter, Johanna, Mertens, Jessica, Schramm, Christoph, Holler, Babett, Mössner, Joachim, Suzuki, Kenji, Yokoyama, Junji, Terai, Shuji, Uter, Wolfgang, Yoneyama, Hiroyuki, Asakura, Hitoshi, and Hibi, Toshifumi

Abstract

Background and Aims Carbohydrate sulfotransferase 15 [CHST15] biosynthesizes sulphated matrix glycosaminoglycans and is implicated in intestinal inflammation and fibrosis. Here, we evaluate the efficacy and safety of the double-stranded RNA oligonucleotide GUT-1, a specific blocker of CHST15, as induction therapy in patients with ulcerative colitis [UC]. Methods In this randomized, double-blind, placebo-controlled, phase 2a study, we enrolled endoscopically active UC patients, refractory to conventional therapy, in five hospital centres across Germany. Patients were randomized 1:1:1 using a block randomized technique to receive a single dosing of 25 nM GUT-1, 250 nM GUT-1, or placebo by endoscopic submucosal injections. The primary outcome measure was improvement of endoscopic lesions at weeks 2 or 4. The secondary outcome measures included clinical and histological responses. Safety was assessed in all patients who received treatment. Results Twenty-eight patients were screened, 24 were randomized, and 21 were evaluated. Endoscopic improvement at weeks 2 or 4 was achieved by 71.4% in the GUT-1 250 nM, 0% in the GUT-1 25 nM, and 28.6% in the placebo group. Clinical remission was shown by 57.1% in the GUT-1 250 nM, 0% in the GUT-1 25 nM, and 14.3% in the placebo groups. Histological improvement was shown by 42.9% in the GUT-1 250 nM, 0% in the GUT-1 25 nM, and 0% in the placebo groups. GUT-1 250 nM reduced CHST15 expression significantly and suppressed mucosal inflammation and fibrosis. GUT-1 application was well tolerated. Conclusion Single dosing by submucosal injection of GUT-1 repressed CHST15 mucosal expression and may represent a novel induction therapy by modulating tissue remodelling in UC. [ABSTRACT FROM AUTHOR]

Published
2024
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37. Clinical and Pharmacokinetic Factors Associated With Adalimumab-Induced Mucosal Healing in Patients With Crohn’s Disease

Author

Andoh, Akira, Ashida, Toshifumi, Endo, Katsuya, Endo, Yutaka, Esaki, Motohiro, Fujita, Hiroshi, Fujiya, Mikihiro, Haruma, Ken, Hibi, Toshifumi, Hiraoka, Sakiko, Hirata, Ichiro, Hisamatsu, Tadakazu, Honda, Yutaka, Iijima, Hideki, Iizuka, Bunei, Ikeya, Kentaro, Inoue, Takuya, Inoue, Syuji, Ishida, Tetsuya, Ishiguro, Yo, Ishihara, Shyunji, Ito, Hiroaki, Iwakiri, Ryuichi, Kagaya, Takashi, Kanai, Takanori, Kashida, Hiroshi, Kato, Shingo, Kato, Jun, Katsurada, Takehiko, Kinjyo, Fukunori, Kobayashi, Kiyonori, Kodama, Mayumi, Kunisaki, Reiko, Kurahara, Koichi, Kurokami, Takafumi, Kyouwon, Lee, Matsuda, Koichiro, Matsueda, Kazuhiro, Matsui, Toshiyuki, Matsumoto, Takayuki, Mitsuyama, Keiichi, Mizokami, Yuji, Motoya, Satoshi, Naito, Yuji, Nakagawa, Tomoo, Nakamura, Shiro, Nakase, Hiroshi, Nojima, Masanori, Nomura, Masafumi, Ogawa, Atsuhiro, Okazaki, Kazuichi, Otsuka, Kazuaki, Sakuraba, Hirotake, Saruta, Masayuki, Sasaki, Makoto, Shirai, Takayuki, Suga, Tomoaki, Sugimura, Kazuhito, Sugiyama, Toshiro, Suzuki, Yasuo, Takeshima, Fuminao, Tamaki, Hiroyuki, Tanaka, Shinji, Tanida, Satoshi, Tominaga, Keiichi, Tomizawa, Taku, Watababe, Kenji, Watanabe, Mamoru, Watanabe, Kenji, Yamamoto, Syojiro, Yamashita, Masaki, Yoshida, Atsushi, Yoshimura, Naoki, and Nagahori, Masakazu

Published
2018
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38. Efficacy of Indigo Naturalis in a Multicenter Randomized Controlled Trial of Patients With Ulcerative Colitis

Author

Naganuma, Makoto, Sugimoto, Shinya, Mizuno, Shinta, Nakazato, Yoshihiro, Fukuda, Tomohiro, Teratani, Toshiaki, Ogata, Haruhiko, Iwao, Yasushi, Kanai, Takanori, Yamasaki, Hiroshi, Mitsuyama, Keiichi, Kobayashi, Taku, Toyonaga, Takahiko, Nakano, Masaru, Hibi, Toshifumi, Yoshimura, Naoki, Sameshima, Yoichi, Ohi, Hidehisa, Hayashi, Ryohei, Ueno, Yoshitaka, Tanaka, Shinji, Bamba, Shigeki, Andoh, Akira, Matsuoka, Katsuyoshi, Watanabe, Mamoru, Saigusa, Keiichiro, Nakazawa, Atsushi, Morohoshi, Yuichi, Koike, Yuji, Imai, Jin, Ichikawa, Hitoshi, Shimoyama, Takahiro, Yamamoto, Takayuki, Takeuchi, Ken, Suzuki, Yasuo, Nagasaka, Mitsuo, Ohmiya, Naoki, Kitano, Atsuo, Ashizuka, Shinya, Inatsu, Haruhiko, Onodera, Kei, Nakase, Hiroshi, Kitamura, Kazuya, Ikeya, Kentaro, Hanai, Hiroyuki, Watanabe, Chikako, Hokari, Ryota, Hirai, Fumihito, Naito, Yuji, Hoshi, Namiko, Kinjo, Fukunori, Ishiguro, Yo, Sasaki, Makoto, Matsumoto, Takayuki, Watanabe, Kenji, Hisamatsu, Tadakazu, Sano, Fumiya, Roberts, Rachel, Abe, Takayuki, Suda, Wataru, Hattori, Masahira, Fukuda, Shinji, and Hirayama, Akiyoshi

Published
2018
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39. Withdrawal of thiopurines in Crohn’s disease treated with scheduled adalimumab maintenance: a prospective randomised clinical trial (DIAMOND2)

Author

Hisamatsu, Tadakazu, Kato, Shingo, Kunisaki, Reiko, Matsuura, Minoru, Nagahori, Masakazu, Motoya, Satoshi, Esaki, Motohiro, Fukata, Norimasa, Inoue, Satoko, Sugaya, Takeshi, Sakuraba, Hirotake, Hirai, Fumihito, Watanabe, Kenji, Kanai, Takanori, Naganuma, Makoto, Nakase, Hiroshi, Suzuki, Yasuo, Watanabe, Mamoru, Hibi, Toshifumi, Nojima, Masanori, Matsumoto, Takayuki, and DIAMOND2 Study Group

Published
2019
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41. Ulcerative colitis

Author

Kobayashi, Taku, Siegmund, Britta, Le Berre, Catherine, Wei, Shu Chen, Ferrante, Marc, Shen, Bo, Bernstein, Charles N., Danese, Silvio, Peyrin-Biroulet, Laurent, and Hibi, Toshifumi

Published
2020
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42. White Blood Cell Counts and Future Relapse in Ulcerative Colitis under Low-Dose Thiopurine Treatment in Real-World Practice: A 3-Year Japanese Multi-Center Retrospective Cohort Study.

Author

Kiyohara, Hiroki, Yamazaki, Hajime, Moriya, Kei, Akimoto, Naohiko, Kawai, Shoichiro, Takenaka, Kento, Fukuda, Tomohiro, Tominaga, Keiichi, Umeno, Junji, Shinzaki, Shinichiro, Honzawa, Yusuke, Takagi, Tomohisa, Ichikawa, Hitoshi, Endo, Toshiyuki, Ozaki, Ryo, Andoh, Akira, Matsuoka, Katsuyoshi, Hibi, Toshifumi, and Kobayashi, Taku

Published
2024
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46. Aortic carboxypeptidase-like protein, a WNT ligand, exacerbates nonalcoholic steatohepatitis

Author

Teratani, Toshiaki, Tomita, Kengo, Suzuki, Takahiro, Furuhashi, Hirotaka, Irie, Rie, Nishikawa, Makoto, Yamamoto, Junji, Hibi, Toshifumi, Miura, Soichiro, Minamino, Tohru, Oike, Yuichi, Hokari, Ryota, and Kanai, Takanori

Subjects
Liver diseases -- Genetic aspects -- Development and progression -- Care and treatment, Cellular proteins -- Health aspects, Cellular signal transduction -- Genetic aspects -- Health aspects, Health care industry
Abstract

Incidence of nonalcoholic steatohepatitis (NASH), which is considered a hepatic manifestation of metabolic syndrome, has been increasing worldwide with the rise in obesity; however, its pathological mechanism is poorly understood. Here, we demonstrate that the hepatic expression of aortic carboxypeptidase-like protein (ACLP), a glycosylated, secreted protein, increases in NASH in humans and mice. Furthermore, we elucidate that ACLP is a ligand, unrelated to WNT proteins, that activates the canonical WNT pathway and exacerbates NASH pathology. In the liver, ACLP is specifically expressed in hepatic stellate cells (HSCs). As fatty liver disease progresses, ACLP expression is enhanced via activation of STAT3 signaling by obesity-related factors in serum. ACLP specifically binds to frizzled-8 and low- density lipoprotein-related receptor 6 to form a ternary complex that activates canonical WNT signaling. Consequently, ACLP activates HSCs by inhibiting PPARy signals. HSC-specific ACLP deficiency inhibits fibrosis progression in NASH by inhibiting canonical WNT signaling in HSCs. The present study elucidates the role of canonical WNT pathway activation by ACLP in NASH pathology, indicating that NASH can be treated by targeting ACLP-induced canonical WNT pathway activation in HSCs., Introduction Nonalcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome. Currently, NAFLD is the most prevalent liver disease in the world, with an estimated 1 billion [...]

Published
2018
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47. Clinical features of chronic enteropathy associated with SLCO2A1 gene: a new entity clinically distinct from Crohn’s disease

Author

Umeno, Junji, Esaki, Motohiro, Hirano, Atsushi, Fuyuno, Yuta, Ohmiya, Naoki, Yasukawa, Shigeyoshi, Hirai, Fumihito, Kochi, Shuji, Kurahara, Koichi, Yanai, Shunichi, Uchida, Keiichi, Hosomi, Shuhei, Watanabe, Kenji, Hosoe, Naoki, Ogata, Haruhiko, Hisamatsu, Tadakazu, Nagayama, Manabu, Yamamoto, Hironori, Abukawa, Daiki, Kakuta, Fumihiko, Onodera, Kei, Matsui, Toshiyuki, Hibi, Toshifumi, Yao, Tsuneyoshi, Kitazono, Takanari, Matsumoto, Takayuki, and The CEAS study group

Published
2018
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50. Evidence-based clinical practice guidelines for inflammatory bowel disease

Author

Matsuoka, Katsuyoshi, Kobayashi, Taku, Ueno, Fumiaki, Matsui, Toshiyuki, Hirai, Fumihito, Inoue, Nagamu, Kato, Jun, Kobayashi, Kenji, Kobayashi, Kiyonori, Koganei, Kazutaka, Kunisaki, Reiko, Motoya, Satoshi, Nagahori, Masakazu, Nakase, Hiroshi, Omata, Fumio, Saruta, Masayuki, Watanabe, Toshiaki, Tanaka, Toshiaki, Kanai, Takanori, Noguchi, Yoshinori, Takahashi, Ken-ichi, Watanabe, Kenji, Hibi, Toshifumi, Suzuki, Yasuo, Watanabe, Mamoru, Sugano, Kentaro, and Shimosegawa, Tooru

Published
2018
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