2024/05/21 更新

写真a

ミズノ カズユキ
水野 和幸
MIZUNO Kazuyuki
所属
医学部附属病院 化学療法部 病院助教
職名
病院助教
外部リンク
 

論文 29

  1. Risk factors for decreased bone mineral density in patients with metabolic dysfunction-associated steatotic liver disease: A cross-sectional study at a health examination center

    Yokoyama S., Honda T., Ishizu Y., Imai N., Ito T., Yamamoto K., Mizuno K., Kojima T., Kariya N., Nakamura M., Kawashima H.

    Clinical Nutrition   43 巻 ( 6 ) 頁: 1425 - 1432   2024年6月

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    記述言語:英語   出版者・発行元:Clinical Nutrition  

    Background & aims: Steatotic liver disease (SLD) is often detected in health examinations. However, although individuals with metabolic dysfunction-associated SLD (MASLD) may have decreased bone mineral density (BMD), the specific risk factors remain unclarified. The objective of this study was to identify the factors associated with decreased BMD in patients with MASLD. Methods: Individuals who underwent abdominal ultrasonography and BMD measurements at our healthcare center were included. The BMD of the calcaneus was assessed using an AOS-10SA bone densitometer. Decreased BMD was defined as a T-score below −1.0 SD or the administration of osteoporosis treatment. SLD was diagnosed based on specific ultrasonographic criteria. Results: A total of 1410 patients were diagnosed with MASLD. The median age was 52 years. Multivariate analysis using a logistic regression model revealed that the independent predictors of decreased BMD were a low body mass index (BMI) or a small waist circumference (odds ratio (OR): 0.48, 95% confidence interval (CI): 0.34–0.67), hypertriglyceridemia (OR: 1.29, 95% CI: 1.00–1.65), and a weak grip strength (OR: 0.98, 95% CI: 0.97–1.00). Subgroup analyses of individuals aged 50 years or older, men, and individuals with a FIB-4 index of 1.3 or greater revealed that the absence of a high BMI or a large waist circumference was associated with decreased BMD. The subgroup analysis of men revealed that a weaker grip strength was associated with decreased BMD. Conclusion: The present study suggested several potential risk factors for decreased BMD in patients with MASLD. Individuals with the abovementioned risk factors should be encouraged to undergo BMD measurement from the perspective of preventive medicine.

    DOI: 10.1016/j.clnu.2024.04.034

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    PubMed

  2. Outcomes of immune checkpoint inhibitor-induced liver toxicity managed by hepatologists in a multidisciplinary toxicity team

    Ito, T; Mizuno, K; Yamamoto, T; Yasuda, T; Yokoyama, S; Yamamoto, K; Imai, N; Ishizu, Y; Honda, T; Hama, M; Kataoka, T; Shimokata, T; Ando, Y; Kawashima, H

    HEPATOLOGY RESEARCH     2024年4月

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    記述言語:英語   出版者・発行元:Hepatology Research  

    Aim: To detect immune-related adverse events (irAEs) early and treat them appropriately, our institute established an irAE-focused multidisciplinary toxicity team in cooperation with various departments. This study aimed to evaluate a consultation system involving a team of hepatologists in terms of its utility for the management of severe immune checkpoint inhibitor (ICI)-induced liver toxicity. Methods: To analyze the diagnosis and treatment of severe ICI-induced liver toxicity (Grade 2 requiring corticosteroid therapy and Grade 3 or higher), we examined patients' clinical courses before and after the hepatologist consultation system was established (pre-period, September 2014 to February 2019; post-period, March 2019 to March 2023). Results: The median follow-up period was 392 days. Of the 1247 patients with advanced malignancies treated with ICIs, 66 developed severe ICI-induced liver toxicity (n = 22 and 44 in the pre- and post-periods, respectively). In the pre-period, hepatologist consultations were sought for 15/22 patients, whereas in the post-period, 42/44 patients were referred to and treated by hepatologists. The time from the onset of liver toxicity to the consultation was significantly shorter in the post-period than in the pre-period (mean 1.9 vs. 6.5 days, respectively; p = 0.012). The number of patients with a biopsy-confirmed diagnosis of ICI-induced liver toxicity was significantly higher in the post-period than in the pre-period (n = 22 vs. n = 3, respectively; p = 0.006). Finally, there were no cases of immune-related cholangitis in the pre-period, compared to five cases in the post-period. Conclusion: A hepatologist consultation system in an irAE-focused multidisciplinary toxicity team is useful for managing severe ICI-induced liver toxicity.

    DOI: 10.1111/hepr.14043

    Web of Science

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    PubMed

  3. 特集 肝疾患-診療のチェックポイント2023 第Ⅰ部 診断のチェックポイント 第5章 肝疾患鑑別診断のチェックポイント 1.薬物性肝障害が疑われるとき

    伊藤 隆徳, 山本 崇文, 水野 和幸, 石上 雅敏, 川嶋 啓揮

    臨床消化器内科   38 巻 ( 7 ) 頁: 799 - 806   2023年6月

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    出版者・発行元:日本メディカルセンター  

    DOI: 10.19020/cg.0000002668

    CiNii Research

  4. Serum osteopontin predicts the response to atezolizumab plus bevacizumab in patients with hepatocellular carcinoma

    Yamauchi, R; Ito, T; Yoshio, S; Yamamoto, T; Mizuno, K; Ishigami, M; Kawashima, H; Yasuda, S; Shimose, S; Iwamoto, H; Yamazoe, T; Mori, T; Kakazu, E; Kawaguchi, T; Toyoda, H; Kanto, T

    JOURNAL OF GASTROENTEROLOGY   58 巻 ( 6 ) 頁: 565 - 574   2023年6月

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    記述言語:英語   出版者・発行元:Journal of Gastroenterology  

    Background: Combination therapy with anti-programmed death-ligand 1 and anti-vascular endothelial growth factor (VEGF) antibodies has become the standard treatment for un-resectable hepatocellular carcinoma (uHCC). We aimed to identify predictive circulating biomarkers for the outcome/response of the combination therapy in uHCC patients. Methods: This prospective multicenter study enrolled 70 patients with uHCC who received atezolizumab and bevacizumab (Atez/Bev). We evaluated 47 circulating proteins in sera before and after 1 and 6 weeks of Atez/Bev therapy by multiplex bead-based immunoassay and ELISA. As controls, we analyzed the sera from 62 uHCC patients before treatment of lenvatinib (LEN) and healthy volunteers (HVs). Results: The disease control rate was 77.1%. Median progression-free survival (PFS) was 5.7 months (95% confidence interval [CI] = 3.8–9.5). The pretreatment levels of osteopontin (OPN), angiopoietin-2, VEGF, S100–calcium-binding protein A8/S100–calcium-binding protein A9, soluble programmed cell death-1, soluble CD163, and 14 cytokines/chemokines were higher in patients with uHCC than in HVs. Among these, pretreatment OPN levels were higher in PD group than in non-PD group for Atez/Bev. The PD rate was higher in high OPN group than in low OPN group. Multivariate analysis identified high pretreatment OPN and high α‐fetoprotein levels as independent predictors of PD. In the sub-analysis of Child–Pugh class A patients, PFS was also shorter in the high OPN group than in the low OPN group. Pretreatment OPN level was not associated with treatment response for LEN. Conclusion: High serum OPN levels were associated with poor response to Atez/Bev in patients with uHCC.

    DOI: 10.1007/s00535-023-01985-w

    Web of Science

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  5. Abdominal pain accompanied by elevated serum inflammatory markers and biliary enzymes for diagnosing immune checkpoint inhibitor-induced sclerosing cholangitis

    Yamamoto, T; Mizuno, K; Ito, T; Yokoyama, S; Yamamoto, K; Imai, N; Ishizu, Y; Honda, T; Ishikawa, T; Kanamori, A; Yasuda, S; Toyoda, H; Yokota, K; Hase, T; Nishio, N; Maeda, O; Ishii, M; Sone, M; Ando, Y; Akiyama, M; Ishigami, M; Kawashima, H

    INVESTIGATIONAL NEW DRUGS   41 巻 ( 3 ) 頁: 512 - 521   2023年6月

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    記述言語:英語   出版者・発行元:Investigational New Drugs  

    Immune-related sclerosing cholangitis (irSC) is relatively rare and its clinical characteristics are not well known. In this study, we aimed to summarize the clinical features of irSC. Clinical data were collected retrospectively from 1,393 patients with advanced malignancy treated with immune-checkpoint inhibitors (ICIs) between August 2014 and October 2021. We analyzed patients with immune-related adverse events of liver injury (liver-irAEs) and compared irSC and non-irSC groups. Sixty-seven patients (4.8%) had a liver-irAE (≥ grade 3) during the follow-up period (median, 262 days). Among these, irSC was observed in eight patients (11.9%). All patients in the irSC group were treated with anti-PD-1/PD-L1 antibodies. Compared with the non-irSC group, the irSC group showed mainly non-hepatocellular liver injury (87.5 % vs 50.8 %, P = 0.065), and had elevated serum inflammatory markers (e.g., CRP and NLR) and biliary enzymes (e.g., GGTP and ALP) at the onset of liver-irAEs. Furthermore, most patients with irSC had abdominal pain. In the non-irSC group, the liver injury of 23 patients improved only with the discontinuation of ICIs, and 22 patients improved with medication including prednisolone (PSL). Conversely, almost all patients (n=7) in the irSC group were treated with PSL, but only two patients experienced an improvement in liver injury. We found that irSC is characterized by a non-hepatocellular type of liver injury with abdominal pain and a high inflammatory response and is refractory to treatment. Further examination by imaging is recommended to detect intractable irSC in cases with these characteristics.

    DOI: 10.1007/s10637-023-01366-3

    Web of Science

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科研費 1

  1. 網羅的遺伝子解析によるirAE肝障害発症メカニズムの探索および治療アルゴリズムの開発

    研究課題/研究課題番号:23K07434  2023年4月 - 2026年3月

    科学研究費助成事業  基盤研究(C)

    水野 和幸

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    担当区分:研究代表者 

    配分額:4680000円 ( 直接経費:3600000円 、 間接経費:1080000円 )

    がん治療において免疫チェックポイント阻害薬 (immune checkpoint inhibitor: ICI)の使用が増加している。ICIは従来の抗がん剤とは異なる副作用である免疫関連有害事象 (immune-related adverse event:irAE)を起こしうる。irAEによる肝障害に対しICI治療の中断と免疫抑制治療が必要となるが、無治療で改善する症例も存在し、ICIの再投与が施行可能なこともある。本研究はirAE肝障害の肝生検組織のRNAを調べ、irAE肝障害のメカニズムの探索、新規治療法の開発ならびにirAE肝障害の治療法や再投与の可否を予測するバイオマーカーを検索する。