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2. Future Possible Changes in Medically Underserved Areas in Japan: A Geographic Information System-Based Simulation Study.

Author

Nakamura, Akihisa, Satoh, Eiji, Suzuki, Tatsuya, Koike, Soichi, and Kotani, Kazuhiko

Subjects
MEDICALLY underserved areas, GEOGRAPHIC information systems, RURAL health services, JAPANESE people, HEALTH care reform
Abstract

Background: A decrease in populations could affect healthcare access and systems, particularly in medically underserved areas (MUAs) where depopulation is becoming more prevalent. This study aimed to simulate the future population and land areas of MUAs in Japan. Methods: This study covered 380,948 1 km meshes, 87,942 clinics, and 8354 hospitals throughout Japan as of 2020. The areas outside a 4 km radius of medical institutions were considered as MUAs, based on the measure of areas in the current Japanese Medical Care Act. Based on the population estimate for a 1 km mesh, the population of mesh numbers of MUAs was predicted for every 10 years from 2020 to 2050 using geographic information system analysis. If the population within a 4 km radius from a medical institution fell below 1000, the institution was operationally assumed to be closed. Results: The number of MUAs was predicted to decrease from 964,310 (0.77% of the total Japanese population) in 2020 to 763,410 (0.75%) by 2050. By 2050, 48,105 meshes (13% of the total meshes in Japan) were predicted to be new MUAs, indicating a 31% increase in MUAs from 2020 to 2050. By 2050, 1601 medical institutions were tentatively estimated to be in close proximity. Conclusions: In Japan, the population of MUAs will decrease, while the land area of MUAs will increase. Such changes may reform rural healthcare policy and systems. [ABSTRACT FROM AUTHOR]

Published
2024
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5. Awareness and information resources concerning emergency telephone consultation services in older adults in an aging community in Japan.

Author

Nakamura, Akihisa and Kotani, Kazuhiko

Subjects
*HEALTH literacy, *INDEPENDENT living, *RESEARCH funding, *INFORMATION resources, *EMERGENCY medical services, *DESCRIPTIVE statistics, *TELEMEDICINE, *MEDICAL consultation, *TELEPHONES, *MEDICAL referrals, *OLD age
Abstract

The article focuses on the awareness and information resources concerning emergency telephone consultation (ETC) services among older adults in an aging community in Japan. It explores the relatively low utilization of ETC services among older adults despite their susceptibility to needing emergency care, highlighting the need to improve awareness and accessibility of these services, particularly through person-to-person interactions.

Published
2024
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8. Low baseline CXCL9 predicts early progressive disease in unresectable HCC with atezolizumab plus bevacizumab treatment

Author

Hosoda, Shunichi, primary, Suda, Goki, additional, Sho, Takuya, additional, Ogawa, Koji, additional, Kimura, Megumi, additional, Yang, Zijian, additional, Yoshida, Sonoe, additional, Kubo, Akinori, additional, Tokuchi, Yoshimasa, additional, Kitagataya, Takashi, additional, Maehara, Osamu, additional, Ohnishi, Shunsuke, additional, Nakamura, Akihisa, additional, Yamada, Ren, additional, Ohara, Masatsugu, additional, Kawagishi, Naoki, additional, Natsuizaka, Mitsuteru, additional, Nakai, Masato, additional, Morikawa, Kenichi, additional, Furuya, Ken, additional, Baba, Masaru, additional, Yamamoto, Yoshiya, additional, Suzuki, Kazuharu, additional, Izumi, Takaaki, additional, Meguro, Takashi, additional, Terashita, Katsumi, additional, Ito, Jun, additional, Miyagishima, Takuto, additional, and Sakamoto, Naoya, additional

Published
2022
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9. Efficacy and Effect on Liver Functional Reserve of Atezolizumab and Bevacizumab for Unresectable Hepatocellular Carcinoma in Patients Who Do Not Meet Eligibility Criteria of IMbrave150

Author

Sho, Takuya, primary, Suda, Goki, additional, Yamamoto, Yoshiya, additional, Furuya, Ken, additional, Baba, Masaru, additional, Ogawa, Koji, additional, Kubo, Akinori, additional, Tokuchi, Yoshimasa, additional, Fu, Qingjie, additional, Yang, Zijian, additional, Kimura, Megumi, additional, Kitagataya, Takashi, additional, Maehara, Osamu, additional, Ohnishi, Shunsuke, additional, Nakamura, Akihisa, additional, Yamada, Ren, additional, Ohara, Masatsugu, additional, Kawagishi, Naoki, additional, Natsuizaka, Mitsuteru, additional, Nakai, Masato, additional, Suzuki, Kazuharu, additional, Izumi, Takaaki, additional, Meguro, Takashi, additional, Terashita, Katsumi, additional, Takagi, Tomofumi, additional, Ito, Jun, additional, Kobayashi, Tomoe, additional, Miyagishima, Takuto, additional, and Sakamoto, Naoya, additional

Published
2022
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10. Case Report: Hereditary Fibrosing Poikiloderma With Tendon Contractures, Myopathy, and Pulmonary Fibrosis (POIKTMP) Presenting With Liver Cirrhosis and Steroid-Responsive Interstitial Pneumonia

Author

Takimoto-Sato, Michiko, primary, Miyauchi, Toshinari, additional, Suzuki, Masaru, additional, Ujiie, Hideyuki, additional, Nomura, Toshifumi, additional, Ikari, Tomoo, additional, Nakamura, Tomohiko, additional, Takahashi, Kei, additional, Matsumoto-Sasaki, Machiko, additional, Kimura, Hirokazu, additional, Kimura, Hiroki, additional, Matsui, Yuichiro, additional, Kitagataya, Takashi, additional, Yamada, Ren, additional, Suzuki, Kazuharu, additional, Nakamura, Akihisa, additional, Nakai, Masato, additional, Sho, Takuya, additional, Ogawa, Koji, additional, Sakamoto, Naoya, additional, Yamaguchi, Naoko, additional, Otsuka, Noriyuki, additional, Tomaru, Utano, additional, and Konno, Satoshi, additional

Published
2022
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11. Effects of nucleos(t)ide analogs on hepatitis B surface antigen reduction with interferon‐lambda 3 induction in chronic hepatitis B patients

Author

Umemura, Machiko, primary, Ogawa, Koji, additional, Morikawa, Kenichi, additional, Kubo, Akinori, additional, Tokuchi, Yoshimasa, additional, Yamada, Ren, additional, Kitagataya, Takashi, additional, Shigesawa, Taku, additional, Shimazaki, Tomoe, additional, Kimura, Megumi, additional, Suzuki, Kazuharu, additional, Nakamura, Akihisa, additional, Ohara, Masatsugu, additional, Kawagishi, Naoki, additional, Izumi, Takaaki, additional, Nakai, Masato, additional, Sho, Takuya, additional, Suda, Goki, additional, Natsuizaka, Mitsuteru, additional, Ono, Kota, additional, Murata, Kazumoto, additional, Sugiyama, Masaya, additional, Mizokami, Masashi, additional, and Sakamoto, Naoya, additional

Published
2022
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12. Low Baseline CXCL9 Predicts Early Progressive Disease in Unresectable HCC with Atezolizumab Plus Bevacizumab Treatment.

Author

Hosoda, Shunichi, Suda, Goki, Sho, Takuya, Ogawa, Koji, Kimura, Megumi, Yang, Zijian, Yoshida, Sonoe, Kubo, Akinori, Tokuchi, Yoshimasa, Kitagataya, Takashi, Maehara, Osamu, Ohnishi, Shunsuke, Nakamura, Akihisa, Yamada, Ren, Ohara, Masatsugu, Kawagishi, Naoki, Natsuizaka, Mitsuteru, Nakai, Masato, Morikawa, Kenichi, and Furuya, Ken

Subjects
ATEZOLIZUMAB, HEPATOCELLULAR carcinoma, BEVACIZUMAB, DISEASE progression, HEPATITIS C, PLATELET-derived growth factor
Abstract

As shown in online supplementary Figure S8, similar to in vitro analysis, the median serum CXCL9 increased in patients with objective response to lenvatinib, and the median changes in serum CXCL9 were significantly higher in patients with objective response to lenvatinib than in those without objective response to lenvatinib. As shown in online supplementary Figure S3, the expression of CXCL9 in HCC was higher in patients with a high serum CXCL9 level compared with that in patients with a relatively lower serum CXCL9 level. As shown in Figure 2a, CXCL9 levels were significantly lower in patients with early PD compared to those in patients without early PD; while CXCL9 levels were similar in patients with or without objective responses. [Extracted from the article]

Published
2023
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13. Theds potential of soluble CD14 in discriminating nonalcoholic steatohepatitis from nonalcoholic fatty liver disease

Author

Nakamura, Akihisa, primary, Yamamoto, Koji, additional, Takeda, Rei, additional, Yamada, Ren, additional, Kubo, Akinori, additional, Morikawa, Kenichi, additional, Ando, Sayaka, additional, Shimazaki, Tomoe, additional, Izumi, Takaaki, additional, Umemura, Machiko, additional, Kitagataya, Takashi, additional, Shigesawa, Taku, additional, Suzuki, Kazuharu, additional, Kimura, Megumi, additional, Nakai, Masato, additional, Sho, Takuya, additional, Suda, Goki, additional, Natsuizaka, Mitsuteru, additional, Ogawa, Koji, additional, Ohnishi, Shunsuke, additional, Sugiyama, Toshiro, additional, Takeda, Hiroshi, additional, and Sakamoto, Naoya, additional

Published
2022
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14. High serum angiopoietin-2 level predicts non-regression of liver stiffness measurement-based liver fibrosis stage after direct-acting antiviral therapy for hepatitis C

Author

Kawagishi, Naoki, Suda, Goki, Kimura, Megumi, Maehara, Osamu, Shimazaki, Tomoe, Yamada, Ren, Kitagataya, Takashi, Shigesawa, Taku, Suzuki, Kazuharu, Nakamura, Akihisa, Ohara, Masatsugu, Umemura, Machiko, Nakai, Masato, Sho, Takuya, Natsuizaka, Mitsuteru, Morikawa, Kenichi, Ogawa, Koji, Kudo, Yusuke, Nishida, Mutsumi, and Sakamoto, Naoya

Subjects
HCV, angiopoietin-2, liver stiffness measurement, DAA
Abstract

Aim Factors associated with improvement of liver fibrosis after successful hepatitis C virus (HCV) eradication by interferon (IFN)-free direct-acting antiviral agents (DAAs) have been not clarified well. Angiopoietin-2 (Ang2) is reported to be associated with vascular leak and inflammation observed in patients with advanced liver fibrosis. Methods In this retrospective study, patients treated with IFN-free DAAs who underwent transient elastography before and at 24-weeks post-treatment and achieved sustained viral response were enrolled. Baseline serum Ang2 was measured, and its relationship with other clinical factors was analyzed. Liver fibrosis stage was defined based on liver stiffness according to a previous report. Predictive factors for regression of liver fibrosis stage after DAA therapy were evaluated. Results Overall, 116 patients were analyzed. Baseline serum Ang2 levels were significantly associated with liver stiffness, spleen index, and liver stiffness-based liver fibrosis stage. Moreover, 75% of patients experienced regression of liver fibrosis stage after DAA therapy. Multivariate analysis revealed that advanced liver fibrosis stage and Ang2 levels were significantly associated with regression of liver fibrosis stage after DAA therapy. In patients with advanced liver fibrosis (F3/4), baseline Ang2 level alone could predict regression of liver fibrosis stage. A baseline Ang2 cut-off value (354?pg/ML) could predict regression of liver fibrosis stage after DAA therapy with high accuracy (sensitivity 0.882, specificity 0.733). Conclusions Evaluation of serum Ang2 levels before DAA therapy is important. Our results provide a novel mechanistic insight into non-regression of liver stiffness after DAA therapy. Long-term and larger studies are required.

Published
2020

15. Early response and safety of atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma in patients who do not meet IMbrave150 eligibility criteria

Author

Sho, Takuya, primary, Suda, Goki, additional, Ogawa, Koji, additional, Kimura, Megumi, additional, Kubo, Akinori, additional, Tokuchi, Yoshimasa, additional, Kitagataya, Takashi, additional, Maehara, Osamu, additional, Ohnishi, Shunsuke, additional, Shigesawa, Taku, additional, Nakamura, Akihisa, additional, Yamada, Ren, additional, Ohara, Masatsugu, additional, Kawagishi, Naoki, additional, Natsuizaka, Mitsuteru, additional, Nakai, Masato, additional, Morikawa, Kenichi, additional, Furuya, Ken, additional, Baba, Masaru, additional, Yamamoto, Yoshiya, additional, Suzuki, Kazuharu, additional, Izumi, Takaaki, additional, Meguro, Takashi, additional, Terashita, Katsumi, additional, Ito, Jun, additional, Miyagishima, Takuto, additional, and Sakamoto, Naoya, additional

Published
2021
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19. Lenvatinib in patients with unresectable hepatocellular carcinoma who do not meet the REFLECT trial eligibility criteria

Author

Sho, Takuya, primary, Suda, Goki, additional, Ogawa, Koji, additional, Shigesawa, Taku, additional, Suzuki, Kazuharu, additional, Nakamura, Akihisa, additional, Ohara, Masatsugu, additional, Umemura, Machiko, additional, Kawagishi, Naoki, additional, Natsuizaka, Mitsuteru, additional, Nakai, Masato, additional, Morikawa, Kenichi, additional, Furuya, Ken, additional, Baba, Masaru, additional, Ito, Jun, additional, Yamamoto, Yoshiya, additional, Kobayashi, Tomoe, additional, Meguro, Takashi, additional, Saga, Akiyoshi, additional, Miyagishima, Takuto, additional, Terasita, Katsumi, additional, Takagi, Tomofumi, additional, Kamiyama, Toshiya, additional, Taketomi, Akinobu, additional, and Sakamoto, Naoya, additional

Published
2020
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20. Computed tomography, not bioelectrical impedance analysis, is the proper method for evaluating changes in skeletal muscle mass in liver disease

Author

Ohara, Masatsugu, primary, Suda, Goki, additional, Kimura, Megumi, additional, Maehara, Osamu, additional, Shimazaki, Tomoe, additional, Shigesawa, Taku, additional, Suzuki, Kazuharu, additional, Nakamura, Akihisa, additional, Kawagishi, Naoki, additional, Nakai, Masato, additional, Sho, Takuya, additional, Natsuizaka, Mitsuteru, additional, Morikawa, Kenichi, additional, Ogawa, Koji, additional, and Sakamoto, Naoya, additional

Published
2020
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21. Lenvatinib suppresses cancer stem-like cells in HCC by inhibiting FGFR1–3 signaling, but not FGFR4 signaling

Author

Shigesawa, Taku, primary, Maehara, Osamu, additional, Suda, Goki, additional, Natsuizaka, Mitsuteru, additional, Kimura, Megumi, additional, Shimazaki, Tomoe, additional, Yamamoto, Koji, additional, Yamada, Ren, additional, Kitagataya, Takashi, additional, Nakamura, Akihisa, additional, Suzuki, Kazuharu, additional, Ohara, Masatsugu, additional, Kawagishi, Naoki, additional, Umemura, Machiko, additional, Nakai, Masato, additional, Sho, Takuya, additional, Morikawa, Kenichi, additional, Ogawa, Koji, additional, Ohnishi, Shunsuke, additional, Sugiyama, Masaya, additional, Mizokami, Masashi, additional, Takeda, Hiroshi, additional, and Sakamoto, Naoya, additional

Published
2020
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22. Baseline angiopoietin‐2 and FGF19 levels predict treatment response in patients receiving multikinase inhibitors for hepatocellular carcinoma

Author

Shigesawa, Taku, primary, Suda, Goki, additional, Kimura, Megumi, additional, Shimazaki, Tomoe, additional, Maehara, Osamu, additional, Yamada, Ren, additional, Kitagataya, Takashi, additional, Suzuki, Kazuharu, additional, Nakamura, Akihisa, additional, Ohara, Masatsugu, additional, Umemura, Machiko, additional, Kawagishi, Naoki, additional, Nakai, Masato, additional, Sho, Takuya, additional, Natsuizaka, Mitsuteru, additional, Morikawa, Kenichi, additional, Ogawa, Koji, additional, and Sakamoto, Naoya, additional

Published
2020
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23. Analysis of the optimal psoas muscle mass index cut‐off values, as measured by computed tomography, for the diagnosis of loss of skeletal muscle mass in Japanese people

Author

Ohara, Masatsugu, primary, Suda, Goki, additional, Kimura, Megumi, additional, Maehara, Osamu, additional, Shimazaki, Tomoe, additional, Shigesawa, Taku, additional, Suzuki, Kazuharu, additional, Nakamura, Akihisa, additional, Kawagishi, Naoki, additional, Nakai, Masato, additional, Sho, Takuya, additional, Natsuizaka, Mitsuteru, additional, Morikawa, Kenichi, additional, Ogawa, Koji, additional, Kobayashi, Tomoe, additional, Uebayashi, Minoru, additional, Takagi, Ryo, additional, Yokota, Isao, additional, Shimamura, Tsuyoshi, additional, and Sakamoto, Naoya, additional

Published
2020
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24. Prevalence, clinical course, and predictive factors of immune checkpoint inhibitor monotherapy‐associated hepatitis in Japan

Author

Kitagataya, Takashi, primary, Suda, Goki, additional, Nagashima, Kazunori, additional, Katsurada, Takehiko, additional, Yamamoto, Koji, additional, Kimura, Megumi, additional, Maehara, Osamu, additional, Yamada, Ren, additional, Shigesawa, Taku, additional, Suzuki, Kazuharu, additional, Nakamura, Akihisa, additional, Ohara, Masatsugu, additional, Umemura, Machiko, additional, Kawagishi, Naoki, additional, Nakai, Masato, additional, Sho, Takuya, additional, Natsuizaka, Mitsuteru, additional, Morikawa, Kenichi, additional, Ogawa, Koji, additional, Ohnishi, Shunsuke, additional, Komatsu, Yoshito, additional, Hata, Hiroo, additional, Takeuchi, Satoshi, additional, Abe, Takashige, additional, Sakakibara‐Konishi, Jun, additional, Teshima, Takanori, additional, Homma, Akihiro, additional, and Sakamoto, Naoya, additional

Published
2020
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25. Tri-antennary tri-sialylated mono-fucosylated glycan of alpha-1 antitrypsin as a non-invasive biomarker for non-alcoholic steatohepatitis: a novel glycobiomarker for non-alcoholic steatohepatitis

Author

Ogawa, Koji, primary, Kobayashi, Takashi, additional, Furukawa, Jun-ichi, additional, Hanamatsu, Hisatoshi, additional, Nakamura, Akihisa, additional, Suzuki, Kazuharu, additional, Kawagishi, Naoki, additional, Ohara, Masatsugu, additional, Umemura, Machiko, additional, Nakai, Masato, additional, Sho, Takuya, additional, Suda, Goki, additional, Morikawa, Kenichi, additional, Baba, Masaru, additional, Furuya, Ken, additional, Terashita, Katsumi, additional, Kobayashi, Tomoe, additional, Onodera, Manabu, additional, Horimoto, Takahiro, additional, Shinada, Keisuke, additional, Tsunematsu, Seiji, additional, Tsunematsu, Izumi, additional, Meguro, Takashi, additional, Mitsuhashi, Tomoko, additional, Hato, Megumi, additional, Higashino, Kenichi, additional, Shinohara, Yasuro, additional, and Sakamoto, Naoya, additional

Published
2020
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27. A prospective comparison between multidetector-row computed tomography and magnetic resonance imaging in the preoperative evaluation of rectal carcinoma

Author

Matsuoka, Hiroyoshi, Nakamura, Akihisa, Masaki, Tadahiko, Sugiyama, Masanori, Takahara, Taro, Hachiya, Junichi, and Atomi, Yutaka

Subjects
Magnetic resonance imaging -- Comparative analysis, Magnetic resonance imaging -- Usage, CT imaging -- Comparative analysis, CT imaging -- Usage, Colorectal cancer -- Diagnosis, Health
Published
2003

30. Safety and efficacy of elbasvir/grazoprevir for the treatment of chronic hepatitis C: current evidence

Author

Morikawa,Kenichi, Nakamura,Akihisa, Shimazaki,Tomoe, and Sakamoto,Naoya

Subjects
Drug Design, Development and Therapy, virus diseases, digestive system diseases
Abstract

Kenichi Morikawa, Akihisa Nakamura, Tomoe Shimazaki, Naoya Sakamoto Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo, Japan Abstract: Treatments for hepatitis C virus (HCV) have advanced greatly, becoming more efficacious with fewer adverse events, due to the availability of direct-acting antiviral agents, which target specific steps in the HCV life cycle. Recently, a combination regimen consisting of the HCV nonstructural protein 5A inhibitor elbasvir (EBR) and the HCV NS3/4A protease inhibitor grazoprevir (GZR) was approved for the treatment of patients with chronic HCV and genotypes (Gts) 1 and 4 in various countries. In Phase III trials, the combination of EBR/GZR (fixed-dose combination table or single agent) for 12 or 16 weeks of treatment with or without ribavirin resulted in a high sustained virological response at 12 weeks in treatment-naïve and treatment-experienced patients with HCV Gt 1a, 1b, 4, or 6, including special populations, such as individuals with advanced chronic kidney disease, HCV-HIV coinfection, and compensated cirrhosis. In this review, we focus on the mode of action, pharmacokinetics, clinical applications, efficacy, and safety profile of EBR/GZR, including special populations who have been considered refractory from the extensive evidence of clinical trials. Keywords: HCV, DAAs, compensated LC, HCV/HIV

Published
2018

31. Effects of resistance‐associated variants in genotype 2 hepatitis C virus on viral replication and susceptibility to antihepatitis C virus drugs

Author

Suda, Goki, primary, Kimura, Megumi, additional, Shigesawa, Taku, additional, Suzuki, Kazuharu, additional, Nakamura, Akihisa, additional, Ohara, Masatsugu, additional, Kawagishi, Naoki, additional, Nakai, Masato, additional, Sho, Takuya, additional, Maehara, Osamu, additional, Shimazaki, Tomoe, additional, Morikawa, Kenichi, additional, Natsuizaka, Mitsuteru, additional, Ogawa, Koji, additional, and Sakamoto, Naoya, additional

Published
2019
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32. Assessing the risk of hepatocellular carcinoma by combining liver stiffness and the controlled attenuation parameter

Author

Izumi, Takaaki, primary, Sho, Takuya, additional, Morikawa, Kenichi, additional, Shigesawa, Taku, additional, Suzuki, Kazuharu, additional, Nakamura, Akihisa, additional, Ohara, Masatsugu, additional, Kawagishi, Naoki, additional, Umemura, Machiko, additional, Shimazaki, Tomoe, additional, Kimura, Megumi, additional, Nakai, Masato, additional, Suda, Goki, additional, Natsuizaka, Mitsuteru, additional, Ogawa, Koji, additional, Kudo, Yusuke, additional, Nishida, Mutsumi, additional, Ono, Kota, additional, Baba, Masaru, additional, Furuya, Ken, additional, and Sakamoto, Naoya, additional

Published
2019
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33. Early response and safety of lenvatinib for patients with advanced hepatocellular carcinoma in a real‐world setting

Author

Sho, Takuya, primary, Suda, Goki, additional, Ogawa, Koji, additional, Kimura, Megumi, additional, Shimazaki, Tomoe, additional, Maehara, Osamu, additional, Shigesawa, Taku, additional, Suzuki, Kazuharu, additional, Nakamura, Akihisa, additional, Ohara, Masatsugu, additional, Umemura, Machiko, additional, Kawagishi, Naoki, additional, Natsuizaka, Mitsuteru, additional, Nakai, Masato, additional, Morikawa, Kenichi, additional, Furuya, Ken, additional, Baba, Masaru, additional, Yamamoto, Yoshiya, additional, Kobayashi, Tomoe, additional, Meguro, Takashi, additional, Saga, Akiyoshi, additional, Miyagishima, Takuto, additional, Yokoo, Hideki, additional, Kamiyama, Toshiya, additional, Taketomi, Akinobu, additional, and Sakamoto, Naoya, additional

Published
2019
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34. FRI-195-Long-term effect of nucleos (t)ide analogs on hepatitis B surface antigen in chronic hepatitis B patients

Author

Morikawa, Kenichi, primary, Umemura, Machiko, additional, Ogawa, Koji, additional, Shigesawa, Taku, additional, Suzuki, Kazuharu, additional, Nakamura, Akihisa, additional, Ohara, Masatsugu, additional, Kawagishi, Naoki, additional, Shimazaki, Tomoe, additional, Kimura, Megumi, additional, Izumi, Takaaki, additional, Nakai, Masato, additional, Sho, Takuya, additional, Suda, Goki, additional, Natsuizaka, Mitsuteru, additional, Ono, Kota, additional, Murata, Kazumoto, additional, Sugiyama, Masaya, additional, Masashi, Mizokami, additional, and Sakamoto, Naoya, additional

Published
2019
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35. Liver steatosis and dyslipidemia after HCV eradication by direct acting antiviral agents are synergistic risks of atherosclerosis

Author

Kawagishi, Naoki, primary, Suda, Goki, additional, Nakamura, Akinobu, additional, Kimura, Megumi, additional, Maehara, Osamu, additional, Suzuki, Kazuharu, additional, Nakamura, Akihisa, additional, Ohara, Masatsugu, additional, Izumi, Takaaki, additional, Umemura, Machiko, additional, Nakai, Masato, additional, Sho, Takuya, additional, Natsuizaka, Mitsuteru, additional, Morikawa, Kenichi, additional, Ogawa, Koji, additional, Kudo, Yusuke, additional, Nishida, Mutsumi, additional, Miyoshi, Hideaki, additional, and Sakamoto, Naoya, additional

Published
2018
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36. Tenofovir–disoproxil–fumarate modulates lipid metabolism via hepatic CD36/PPAR-alpha activation in hepatitis B virus infection.

Author

Suzuki, Kazuharu, Suda, Goki, Yamamoto, Yoshiya, Furuya, Ken, Baba, Masaru, Nakamura, Akinobu, Miyoshi, Hideaki, Kimura, Megumi, Maehara, Osamu, Yamada, Ren, Kitagataya, Takashi, Yamamoto, Koji, Shigesawa, Taku, Nakamura, Akihisa, Ohara, Masatsugu, Kawagishi, Naoki, Nakai, Masato, Sho, Takuya, Natsuizaka, Mitsuteru, and Morikawa, Kenichi

Subjects
LIPID metabolism, HEPATITIS B virus, VIRUS diseases, BLOOD cholesterol, DYSLIPIDEMIA, PROPENSITY score matching, CHRONIC hepatitis B
Abstract

Background: Entecavir and tenofovir–disoproxil–fumarate are first-line nucleos(t)ide analogs (NA) for treatment of hepatitis B virus (HBV) infections; however, their long-term administration can impact extrahepatic organs. Herein, we sought to examine the effect of NA on lipid metabolism while also characterizing the associated mechanism. Methods: A retrospective study was performed on HBV patients administered entecavir or tenofovir–disoproxil–fumarate. Patient clinical information, as well as their preserved serum samples obtained at baseline and 6–12 months after treatment initiation, were analyzed. A 1:1 propensity score matching was applied to the assignment of tenofovir–disoproxil–fumarate or entecavir treatment. Changes in serum cholesterol, including oxidized-LDL, were analyzed. Subsequently, in vitro analysis elucidated the mechanism associated with the effect of NAs on lipid metabolism. Results: Administration of tenofovir–disoproxil–fumarate, not entecavir, to chronic HBV patients, decreased serum cholesterol levels, including non-HDL and oxidized-LDL, which are strongly associated with arteriosclerosis. In vitro analysis revealed that tenofovir–disoproxil–fumarate reduced supernatant cholesterol, and upregulated the scavenger receptor, CD36, in hepatocytes. Meanwhile, silencing of hepatic CD36 increased supernatant cholesterol and negated the cholesterol-reducing effect of tenofovir–disoproxil–fumarate in HepG2-cells. Reporter, microarray, and RT-PCR analyses further revealed that tenofovir–disoproxil–fumarate treatment activates PPAR-α-mediated signaling, and upregulates PPAR-α target genes, including CPT1 and CD36. Alternatively, silencing of PPAR-α reversed the effects of tenofovir–disoproxil–fumarate on CD36. Conclusions: Tenofovir–disoproxil–fumarate modulates lipid metabolism by upregulating hepatic CD36 via PPAR-α activation. Since dyslipidemia could be associated with arteriosclerosis and hepatocarcinogenesis, these discoveries provide novel insights into anti-HBV therapies, as well as the associated extrahepatic effects of NA. [ABSTRACT FROM AUTHOR]

Published
2021
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37. Lenvatinib suppresses cancer stem-like cells in HCC by inhibiting FGFR1–3 signaling, but not FGFR4 signaling.

Author

Shigesawa, Taku, Maehara, Osamu, Suda, Goki, Natsuizaka, Mitsuteru, Kimura, Megumi, Shimazaki, Tomoe, Yamamoto, Koji, Yamada, Ren, Kitagataya, Takashi, Nakamura, Akihisa, Suzuki, Kazuharu, Ohara, Masatsugu, Kawagishi, Naoki, Umemura, Machiko, Nakai, Masato, Sho, Takuya, Morikawa, Kenichi, Ogawa, Koji, Ohnishi, Shunsuke, and Sugiyama, Masaya

Subjects
FIBROBLAST growth factor receptors, CANCER cells, SORAFENIB, SMALL interfering RNA, FIBROBLAST growth factors
Abstract

In hepatocellular carcinoma (HCC), a subset of cells defined by high CD44 and CD133 expression has been reported to possess cancer stem-like cell (CSC) characteristics and to be associated with a poor prognosis. Since the approval of the multikinase inhibitor, lenvatinib, for patients with unresectable HCC, two such inhibitors (sorafenib and lenvatinib) have been employed as first-line systemic chemotherapeutics for these patients. Based on differences in the kinase-affinity profiles between these two drugs, evidence has suggested that both exert different effects on HCC, although these differences are not fully characterized. In this study, using in vitro and a preclinical in vivo xenograft mouse model, we showed that lenvatinib alone (not sorafenib or the cytotoxic agent, 5-fluorouracil) diminished CD44High/CD133High CSCs in HCC. Furthermore, western blotting and reverse transcriptase-polymerase chain reaction analysis revealed that the expression of fibroblast growth factor receptor (FGFR)-1–4 differed between CD44High/CD133High CSCs and control cells. Analysis of the effects of selective FGFR inhibitors and FGFR small interfering RNAs on CSCs in HCC revealed that lenvatinib diminished CSCs in HCC by inhibiting FGFR1–3 signaling, however, FGFR4 signaling was not impacted. Finally, we showed that FGF2 and FGF19 were involved in maintaining CD44High/CD133High CSCs in HCC, potentially, via FGFR1–3. The findings provide novel mechanistic insights into the effects of lenvatinib on CSCs in HCC and provide clues for developing effective targeted therapies against CSCs in HCC. [ABSTRACT FROM AUTHOR]

Published
2021
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38. Early response and safety of lenvatinib for patients with advanced hepatocellular carcinoma in a real‐world setting.

Author

Sho, Takuya, Suda, Goki, Ogawa, Koji, Kimura, Megumi, Shimazaki, Tomoe, Maehara, Osamu, Shigesawa, Taku, Suzuki, Kazuharu, Nakamura, Akihisa, Ohara, Masatsugu, Umemura, Machiko, Kawagishi, Naoki, Natsuizaka, Mitsuteru, Nakai, Masato, Morikawa, Kenichi, Furuya, Ken, Baba, Masaru, Yamamoto, Yoshiya, Kobayashi, Tomoe, and Meguro, Takashi

Subjects
LIVER cancer, CANCER chemotherapy, CLINICAL trials
Abstract

Background and Aim: Lenvatinib has been recently approved as a first‐line systematic therapy for patients with advanced hepatocellular carcinoma (HCC) based on the results of the phase 3 clinical trial REFLECT. This trial excluded patients with a history of systemic chemotherapy, bile duct invasion, and Child‐Pugh grade B. We aimed to investigate the efficacy and safety of lenvatinib for these patients and in the real‐world setting. Methods: Among patients who were administered lenvatinib for advanced HCC between April and October 2018 in Hokkaido University Hospital and related hospitals, we evaluated those who were followed for more than 2 months and whose treatment response was evaluated via dynamic computed tomography at baseline and 2 months after treatment initiation. Meanwhile, patients were excluded if they had decompensated liver cirrhosis, were followed up less than 2 months, or were not evaluated at 2 months. Patients were also stratified according to compliance with the REFLECT inclusion criteria for further analysis. Results: A total of 41 patients were included; more than 50% did not meet the REFLECT inclusion criteria. In total, 5 (12.2%), 20 (48.8%), 12 (29.3%), and 4 (9.3%) showed complete response, partial response, stable disease, and progressive disease, respectively. The objective response rate was 61.2%. The objective response rate and disease control rate were similar between patients who did and did not meet the REFLECT inclusion criteria. Moreover, the safety profile was also similar between the two patient groups. Conclusion: Lenvatinib showed high early response rate and tolerability in patients with advanced HCC. Favorable outcomes were similarly observed in patients who did not meet the REFLECT inclusion criteria. [ABSTRACT FROM AUTHOR]

Published
2020
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39. Entecavir treatment of hepatitis B virus‐infected patients with severe renal impairment and those on hemodialysis.

Author

Suzuki, Kazuharu, Suda, Goki, Yamamoto, Yoshiya, Furuya, Ken, Baba, Masaru, Kimura, Megumi, Maehara, Osamu, Shimazaki, Tomoe, Yamamoto, Koji, Shigesawa, Taku, Nakamura, Akihisa, Ohara, Masatsugu, Kawagishi, Naoki, Nakai, Masato, Sho, Takuya, Natsuizaka, Mitsuteru, Morikawa, Kenichi, Ogawa, Koji, and Sakamoto, Naoya

Subjects
CHRONIC hepatitis B, HEPATITIS B, HEPATITIS B virus, ALANINE aminotransferase, GLOMERULAR filtration rate, CHRONIC kidney failure
Abstract

Aim: Entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF) are first‐line nucleos(t)ide analogues for hepatitis B virus (HBV)‐infected patients. However, consecutive TDF treatment causes renal dysfunction, and the safety and efficacy of TAF have not been established in severe renal dysfunction patients, including hemodialysis patients. The efficacy and safety of ETV in these populations has not been clarified. The study aimed to clarify this. Methods: In this retrospective multicenter study, between 2006 and 2018, a total of 567 HBV‐infected patients treated with ETV monotherapy were screened. Patients were included if >20 years old, treated with ETV monotherapy for >1 year, and had proper clinical information. The efficacy of ETV and changes in renal function were evaluated according to renal function. Results: A total of 273 patients were included: 9.2% (25/273), 1.8% (5/273), and 3.7% (10/273) had chronic kidney disease (CKD) stage G3, CKD stage G4/5, and were on hemodialysis, respectively. Overall, 84.2%, 94.0%, and 96.2% of patients experienced serum HBV‐DNA disappearance at 1, 2, and 3 years, respectively, after treatment initiation. In patients with CKD stage G3–5, estimated glomerular filtration rate tended to restore with time, which was in contrast to patients without renal dysfunction. The rate of disappearance in serum HBV‐DNA, alanine transaminase normalization, and virological breakthrough was similar between patients with or without renal dysfunction. ETV showed high efficacy for all 10 hemodialysis patients without virological breakthrough. Conclusions: Entecavir for HBV‐infected patients with severe renal dysfunction, including hemodialysis patients, is highly effective and does not affect renal function. [ABSTRACT FROM AUTHOR]

Published
2019
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40. L‐Carnitine Suppresses Loss of Skeletal Muscle Mass in Patients With Liver Cirrhosis

Author

Ohara, Masatsugu, primary, Ogawa, Koji, additional, Suda, Goki, additional, Kimura, Megumi, additional, Maehara, Osamu, additional, Shimazaki, Tomoe, additional, Suzuki, Kazuharu, additional, Nakamura, Akihisa, additional, Umemura, Machiko, additional, Izumi, Takaaki, additional, Kawagishi, Naoki, additional, Nakai, Masato, additional, Sho, Takuya, additional, Natsuizaka, Mitsuteru, additional, Morikawa, Kenichi, additional, Ohnishi, Shunsuke, additional, and Sakamoto, Naoya, additional

Published
2018
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44. Potential accessibility scores for hospital care in a province of Japan: GIS-based ecological study of the two-step floating catchment area method and the number of neighborhood hospitals.

Author

Takashi Nakamura, Akihisa Nakamura, Kengo Mukuda, Masanori Harada, Kazuhiko Kotani, Nakamura, Takashi, Nakamura, Akihisa, Mukuda, Kengo, Harada, Masanori, and Kotani, Kazuhiko

Subjects
HOSPITAL care evaluation, HEALTH services accessibility, HOSPITALS, PRIMARY health care, GEOGRAPHIC information systems, FAMILY medicine, MEDICALLY underserved areas, HOSPITAL statistics, HEALTH service areas, STATISTICS
Abstract

Background: For achieving equity of the accessibility to primary healthcare, measuring potential geographical accessibility is essential. The provider-to-population ratio is the most frequently used measure. However, it is difficult to be used in closer region because it does not take into consideration the people and health services beyond its boundary. In order to overcome this problem, we measured the potential access to hospital, using both distance measures and the enhanced two-step floating catchment area (E2SFCA) method. The aim of this study was to compare the number of hospitals in the neighborhood and the E2SFCA score with regard to the amount and equity for access to hospitals.Methods: This descriptive study used publicly available data from 2010. The E2SFCA score and number of neighborhood hospitals were obtained from Tochigi province in Japan using a geographic information system. Dataset of four measures by each census tract was obtained. The measures were E2SFCA score, number of hospitals within the 5 km range, number of hospitals within the 10 km range, and number of hospitals within the 15 km range. Correlation and disparity analyses with the Lorenz curve and Gini coefficient were performed.Results: The measures were obtained in a smaller area than municipality considering adjacent areas using a geographical approach. The E2SFCA score was 5.3 [3.2-7.3] hospitals/million (median [quantile range]), compared to 5.6 hospitals/million in total for the given district. The median number of hospitals within the 5 km, 10 km, and 15 km ranges were 1, 39, and 47, respectively. There was no hospital within the 5 km range in one third of the blocks. Both the number of hospitals within the 10 km range and those within the 15 km range were well correlated. Regional difference became smaller as the distance to count the number of hospitals increased. The gap between small number of hospitals and the high E2SFCA score indicated the location of community hospital in depopulated areas.Conclusions: The E2SFCA method is superior for analyzing spatial access to hospital, because it provides information in the closer sub-regions. Regional differences were hardly seen in access to hospital beyond the 10 km range. Further studies in other regions and countries are needed for precise assessment. [ABSTRACT FROM AUTHOR]

Published
2017
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