2024/02/05 更新

写真a

ヨコヤマ シンヤ
横山 晋也
YOKOYAMA Shinya
所属
医学部附属病院 消化器内科 病院助教
職名
病院助教

学位 1

  1. 博士(医学) ( 2020年3月   名古屋大学 ) 

研究キーワード 3

  1. NAFLD

  2. 門脈圧亢進症

  3. 肝疾患

研究分野 1

  1. ライフサイエンス / 消化器内科学

学歴 2

  1. 名古屋大学   大学院医学系研究科 総合医学専攻

    2016年4月 - 2020年3月

  2. 北海道大学   医学部

    2002年4月 - 2008年3月

所属学協会 6

  1. 日本内科学会   総合内科専門医 認定医

  2. 日本消化器病学会   専門医 指導医

  3. 日本肝臓学会   専門医 指導医 西部会評議員

  4. 日本消化器内視鏡学会   専門医 指導医

  5. 日本門脈圧亢進症学会   技術認定取得者(内視鏡治療)

  6. 日本小児外科学会

▼全件表示

受賞 1

  1. 遼太郎ちゃん基金優秀演題賞

    日本胆道閉鎖症研究会  

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    受賞区分:国内学会・会議・シンポジウム等の賞 

 

論文 34

  1. Successful Treatment with Steroids in a Patient with Vanishing Bile Duct Syndrome and Acute Tubular Necrosis.

    Mizuno F, Imai N, Yasuda K, Yokoyama S, Yamamoto K, Ito T, Ishizu Y, Honda T, Ishigami M, Kawashima H

    Internal medicine (Tokyo, Japan)   63 巻 ( 1 ) 頁: 57 - 61   2024年1月

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    記述言語:英語   出版者・発行元:Internal Medicine  

    Vanishing bile duct syndrome (VBDS) is a rare but potentially serious cholestatic liver disease caused by various etiologies, including drugs. We herein report a complicated case of VBDS with acute tubular necrosis (ATN) that improved significantly with steroid treatment. An Asian man in his 30s was admitted with the acute onset of severe jaundice and a decline in the renal function. Although initial treatment with ursodeoxycholic acid did not reduce jaundice or renal dysfunction, steroid treatment remarkably improved the VBDS and ATN to within the respective normal ranges. Steroid treatment can be considered in cases of VBDS that appear to have an immune-mediated cause.

    DOI: 10.2169/internalmedicine.1826-23

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  2. A new criterion including the aspartate aminotransferase-to-platelet ratio index and liver and spleen stiffness to rule out varices needing treatment in children with biliary atresia: Modification of the Baveno VII criteria

    Yokoyama, S; Ishizu, Y; Honda, T; Imai, N; Ito, T; Yamamoto, K; Muto, H; Shirota, C; Tainaka, T; Sumida, W; Makita, S; Takada, S; Nakagawa, Y; Maeda, T; Nakamura, M; Ishigami, M; Uchida, H; Kawashima, H

    HEPATOLOGY RESEARCH     2023年10月

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

    Aims: Biliary atresia (BA) is a congestive biliary disease that develops in the neonatal period or early infancy. It may present with portal hypertension and varices needing treatment (VNT) even after successful Kasai portoenterostomy. This study aimed to stratify the risk of VNT in children and adolescents with BA. Methods: In this prospective cross-sectional study, we measured liver stiffness (LS) and spleen stiffness (SS) by two-dimensional shear wave elastography and checked for VNT endoscopically in 53 patients with BA who attended for follow-up between July 2018 and September 2022. Varices needing treatment were defined as large esophageal varices, esophageal varices of any size with red color signs, and/or gastric varices along the cardia. Results: Twenty-five patients (aged 0–18 years) had VNT. Eighteen patients met the Baveno VI criteria (LS <20 kPa; platelet count >150 000/L) and were deemed to be at low risk of VNT (spared endoscopies) while three had missed VNT (16.7%). Applying the Baveno VII criteria, which combines the SS cut-off value of 40 kPa with the Baveno VI criteria, resulted in five missed VNTs among 22 spared endoscopies (22.7%). A modification of the Baveno VII criteria using the aspartate aminotransferase-to-platelet ratio index (APRI) instead of the platelet count with cut-off values of 25 kPa, 30 kPa, and 1.04 for LS, SS, and APRI, respectively, missed only one VNT (5.0%) among 20 spared endoscopies. Conclusions: A novel diagnostic criterion that combines LS, SS, and APRI reduced the risk of missing VNT to 5% in children and adolescents with BA.

    DOI: 10.1111/hepr.13976

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  3. Clinical course and prognosis of patients with hepatocellular carcinoma and haemophilia

    Matsuda, N; Imai, N; Yokoyama, S; Yamamoto, K; Ito, T; Ishizu, Y; Honda, T; Okamoto, S; Kanematsu, T; Suzuki, N; Matsushita, T; Ishigami, M; Kawashima, H

    EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY   35 巻 ( 10 ) 頁: 1211 - 1215   2023年10月

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

    Introduction Although patients with haemophilia are known to develop hepatocellular carcinoma (HCC) at a lower age than patients without, there are few reports on the clinical course and prognosis of HCC. Aim We aimed to investigate the clinical course and prognosis of patients with HCC and haemophilia. Methods Twenty-two patients with haemophilia, who were initially diagnosed with HCC between 2003 and 2021, were included. Their clinical courses and prognoses were retrospectively analysed. The results were compared with those of the 24th Nationwide Follow-up Survey of Primary Liver Cancer. Results All 22 patients were male; of these, 20 patients had haemophilia A, and 2 had haemophilia B. The mean age of diagnosis was 63 years (range 45-78 years) which is lower than the mean of 72 years reported in the Nationwide Survey. The mean diameter of the largest tumour was 30 mm (range 11-70 mm), and 18 tumours (82%) were solitary at the initial diagnosis. Standard treatments for HCC were performed in all patients. Sixty-one transarterial chemoembolisation, 28 RFA, 10 hepatectomies, and 2 radiation treatments were performed, and molecular-targeted agents were administered to 5 patients during their clinical courses. No deaths were associated with complications of HCC treatments. The median survival time after initial treatment was 6.4 years (range 0.9-18.7 years) which did not differ much from the median survival time of 5.8 years in the Nationwide Survey. Conclusion Standard treatment for HCC could improve the prognosis of patients with HCC and haemophilia.

    DOI: 10.1097/MEG.0000000000002628

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  4. Impact of elobixibat on liver tumors, microbiome, and bile acid levels in a mouse model of nonalcoholic steatohepatitis

    Sugiyama, Y; Yamamoto, K; Honda, T; Kato, A; Muto, H; Yokoyama, S; Ito, T; Imai, N; Ishizu, Y; Nakamura, M; Asano, T; Enomoto, A; Zaitsu, K; Ishigami, M; Fujishiro, M; Kawashima, H

    HEPATOLOGY INTERNATIONAL   17 巻 ( 6 ) 頁: 1378 - 1392   2023年9月

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

    Background: Elevated bile acid levels have been associated with liver tumors in fatty liver. Ileal bile acid transporter inhibitors may inhibit bile acid absorption in the distal ileum and increase bile acid levels in the colon, potentially decreasing the serum and hepatic bile acid levels. This study aimed to investigate the impact of these factors on liver tumor. Methods: C57BL/6J mice received a one-time intraperitoneal injection of 25-mg/kg diethylnitrosamine. They were fed a choline-deficient high-fat diet for 20 weeks starting from 8 weeks of age, with or without elobixibat (EA Pharma, Tokyo, Japan). Results: Both groups showed liver fat accumulation and fibrosis, with no significant differences between the two groups. However, mice with elobixibat showed fewer liver tumors. The total serum bile acid levels, including free, tauro-conjugated, glyco-conjugated, and tauro-α/β-muricholic acids in the liver, were noticeably reduced following elobixibat treatment. The proportion of gram-positive bacteria in feces was significantly lower in the group treated with elobixibat (5.4%) than in the group without elobixibat (33.7%). Conclusion: Elobixibat suppressed tumor growth by inhibiting bile acid reabsorption, and decreasing total bile acid and primary bile acid levels in the serum and liver. Additionally, the presence of bile acids in the colon may have led to a significant reduction in the proportion of gram-positive bacteria, potentially resulting in decreased secondary bile acid synthesis.

    DOI: 10.1007/s12072-023-10581-2

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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

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  6. Pretreatment Proteinuria Predicts the Prognosis of Patients Receiving Systemic Therapy for Unresectable Hepatocellular Carcinoma

    Mizuno, K; Imai, N; Yamamoto, T; Yokoyama, S; Yamamoto, K; Ito, T; Ishizu, Y; Honda, T; Kuzuya, T; Ishigami, M; Kawashima, H

    CANCERS   15 巻 ( 10 )   2023年5月

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    記述言語:英語   出版者・発行元:Cancers  

    Background: Proteinuria is a common adverse event in systemic therapy for hepatocellular carcinoma (HCC). However, whether the presence of pretreatment proteinuria affects the clinical course is still unclear. Method: From 2011 to 2022, 321 patients with unresectable HCC who were treated with systemic therapy as first-line treatment were enrolled in this study. We retrospectively analyzed the presence of pretreatment proteinuria and the treatment course of systemic therapy. Results: In the cohort, 190 patients were tested for proteinuria qualitatively within 3 months before systemic therapy; 75 were treated with sorafenib, 72 were treated with lenvatinib, and 43 were treated with atezolizumab plus bevacizumab. Overall survival tended to be longer for patients treated with lenvatinib and significantly longer with atezolizumab plus bevacizumab in patients without pretreatment proteinuria but not for those treated with sorafenib. Further analysis was performed in 111 patients treated with lenvatinib or atezolizumab plus bevacizumab who had proteinuria measured quantitatively. Multivariate analysis including proteinuria, liver function, and HCC stage revealed that the severity of proteinuria was an independent predictor of prognosis. Conclusion: Pretreatment proteinuria predicts a poorer prognosis in patients with unresectable HCC treated with lenvatinib or atezolizumab plus bevacizumab but not in those treated with sorafenib.

    DOI: 10.3390/cancers15102853

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  7. Distinct features of two lipid droplets types in cell nuclei from patients with liver diseases

    Imai, N; Ohsaki, Y; Cheng, JL; Zhang, JJ; Mizuno, F; Tanaka, T; Yokoyama, S; Yamamoto, K; Ito, T; Ishizu, Y; Honda, T; Ishigami, M; Wake, H; Kawashima, H

    SCIENTIFIC REPORTS   13 巻 ( 1 ) 頁: 6851   2023年4月

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    記述言語:英語   出版者・発行元:Scientific Reports  

    Lipid droplets (LDs) have been observed in the nuclei of hepatocytes; however, their significance in liver disease remains unresolved. Our purpose was to explore the pathophysiological features of intranuclear LDs in liver diseases. We included 80 patients who underwent liver biopsies; the specimens were dissected and fixed for electron microscopy analysis. Depending on the presence of adjacent cytoplasmic invagination of the nuclear membrane, LDs in the nuclei were classified into two types: nucleoplasmic LDs (nLDs) and cytoplasmic LD invagination with nucleoplasmic reticulum (cLDs in NR). nLDs were found in 69% liver samples and cLDs in NR were found in 32%; no correlation was observed between the frequencies of the two LD types. nLDs were frequently found in hepatocytes of patients with nonalcoholic steatohepatitis, whereas cLDs in NR were absent from the livers of such patients. Further, cLDs in NR were often found in hepatocytes of patients with lower plasma cholesterol level. This indicates that nLDs do not directly reflect cytoplasmic lipid accumulation and that formation of cLDs in NR is inversely correlated to the secretion of very low-density lipoproteins. Positive correlations were found between the frequencies of nLDs and endoplasmic reticulum (ER) luminal expansion, suggesting that nLDs are formed in the nucleus upon ER stress. This study unveiled the presence of two distinct nuclear LDs in various liver diseases.

    DOI: 10.1038/s41598-023-33977-4

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  8. Proteomic Analysis Reveals Changes in Tight Junctions in the Small Intestinal Epithelium of Mice Fed a High-Fat Diet

    Muto, H; Honda, T; Tanaka, T; Yokoyama, S; Yamamoto, K; Ito, T; Imai, N; Ishizu, Y; Maeda, K; Ishikawa, T; Adachi, S; Sato, C; Tsuji, NM; Ishigami, M; Fujishiro, M; Kawashima, H

    NUTRIENTS   15 巻 ( 6 )   2023年3月

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    記述言語:英語   出版者・発行元:Nutrients  

    The impact of a high-fat diet (HFD) on intestinal permeability has been well established. When bacteria and their metabolites from the intestinal tract flow into the portal vein, inflammation in the liver is triggered. However, the exact mechanism behind the development of a leaky gut caused by an HFD is unclear. In this study, we investigated the mechanism underlying the leaky gut related to an HFD. C57BL/6J mice were fed an HFD or control diet for 24 weeks, and their small intestine epithelial cells (IECs) were analyzed using deep quantitative proteomics. A significant increase in fat accumulation in the liver and a trend toward increased intestinal permeability were observed in the HFD group compared to the control group. Proteomics analysis of the upper small intestine epithelial cells identified 3684 proteins, of which 1032 were differentially expressed proteins (DEPs). Functional analysis of DEPs showed significant enrichment of proteins related to endocytosis, protein transport, and tight junctions (TJ). Expression of Cldn7 was inversely correlated with intestinal barrier function and strongly correlated with that of Epcam. This study will make important foundational contributions by providing a comprehensive depiction of protein expression in IECs affected by HFD, including an indication that the Epcam/Cldn7 complex plays a role in leaky gut.

    DOI: 10.3390/nu15061473

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  9. Endoscopic injection sclerotherapy with polidocanol for cardiac varices in children and adolescents.

    Yokoyama S, Ishizu Y, Honda T, Imai N, Ito T, Yamamoto K, Hinoki A, Sumida W, Shirota C, Tainaka T, Makita S, Yokota K, Uchida H, Ishigami M

    Archives de pediatrie : organe officiel de la Societe francaise de pediatrie   30 巻 ( 2 ) 頁: 109 - 112   2023年2月

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    記述言語:英語   出版者・発行元:Archives de Pediatrie  

    Background: Like esophageal varices, cardiac varices are often treated with endoscopic variceal ligation (EVL). However, we previously reported that EVL for cardiac varices may be associated with a high risk of rebleeding from the ulcer if the O-ring spontaneously drops off early. The efficacy and safety of para-variceal endoscopic injection sclerotherapy (EIS) with polidocanol for the treatment of cardiac varices in children and adolescents were evaluated. Methods: Eleven patients under 18 years of age with portal hypertension who underwent para-variceal EIS with polidocanol for cardiac varices with red signs, which were considered to be at high risk of bleeding, were retrospectively reviewed. Results: One session of para-variceal polidocanol-EIS was performed for each of the 11 patients. One patient experienced temporary hypoxia due to aspiration of saliva when the tracheal intubation tube was removed after the procedure but recovered by endotracheal suctioning; there were no other adverse events. In six of the eight cases in which efficacy could be evaluated, eradication of cardiac varices was achieved. Conclusion: Para-variceal polidocanol-EIS may be considered instead of EVL for small cardiac varices with red signs in pediatric patients with cardiac varices.

    DOI: 10.1016/j.arcped.2022.11.016

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  10. The presence of high-risk varices after sclerotherapy in biliary atresia.

    Yokoyama S, Ishizu Y, Honda T, Imai N, Ito T, Yamamoto K, Shirota C, Tainaka T, Sumida W, Makita S, Takimoto A, Nakagawa Y, Takada S, Ishigami M, Uchida H, Kawashima H

    Pediatrics international : official journal of the Japan Pediatric Society     頁: e15454   2022年12月

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    記述言語:英語  

    DOI: 10.1111/ped.15454

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  11. Biochemical markers to predict the development of gastrointestinal bleeding and esophageal varices after portoenterostomy in biliary atresia

    Sumida Wataru, Tainaka Takahisa, Shirota Chiyoe, Yokota Kazuki, Makita Satoshi, Okamoto Masamune, Takimoto Aitaro, Yasui Akihiro, Takada Shunya, Nakagawa Yoichi, Kato Daiki, Yokoyama Shinya, Ishizu Yoji, Amano Hizuru, Guo Yaohui, Hinoki Akinari, Uchida Hiroo

    PEDIATRIC SURGERY INTERNATIONAL   38 巻 ( 12 ) 頁: 1799 - 1805   2022年12月

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    記述言語:英語   出版者・発行元:Pediatric Surgery International  

    Purpose: Gastrointestinal bleeding (GIB) due to esophageal varices (EV) is one of the factors that negatively impact native liver survival of patients with biliary atresia (BA). Gastrointestinal fibroscopy (GIF) is usually used to determine the presence of EVs; however, it requires general anesthesia. The aim of this study is to search for markers in blood tests obtained during routine check-ups that can predict the development of GIB. Methods: Data of patients with BA who underwent portoenterostomy at our hospital from 2014 to 2020 were retrospectively reviewed. The patients’ data were assigned to three groups according to specific time points: Group B, which included data at GIB; Group NB-T, which included data at GIF and EV treatment; and Group NB-NT, which included data at GIF without treatment. The data in Group B were compared to those of other groups. Results: In our study, GIB occurred in 11 patients, and 12 cases and 8 cases were classified into Groups NB-NT and NB-T, respectively. Compared with the other groups, only ChE and M2BPGi in Group B showed statistically significant differences. Conclusions: ChE and M2BPGi are useful for predicting GIB.

    DOI: 10.1007/s00383-022-05243-7

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  12. Clustering using unsupervised machine learning to stratify the risk of immune-related liver injury

    Yamamoto Takafumi, Morooka Hikaru, Ito Takanori, Ishigami Masatoshi, Mizuno Kazuyuki, Yokoyama Shinya, Yamamoto Kenta, Imai Norihiro, Ishizu Yoji, Honda Takashi, Yokota Kenji, Hase Tetsunari, Maeda Osamu, Hashimoto Naozumi, Ando Yuichi, Akiyama Masashi, Kawashima Hiroki

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY   38 巻 ( 2 ) 頁: 251 - 258   2022年11月

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    記述言語:英語   出版者・発行元:Journal of Gastroenterology and Hepatology (Australia)  

    Background and Aim: Immune-related liver injury (liver-irAE) is a clinical problem with a potentially poor prognosis. Methods: We retrospectively collected clinical data from patients treated with immune checkpoint inhibitors between September 2014 and December 2021 at the Nagoya University Hospital. Using an unsupervised machine learning method, the Gaussian mixture model, to divide the cohort into clusters based on inflammatory markers, we investigated the cumulative incidence of liver-irAEs in these clusters. Results: This study included a total of 702 patients. Among them, 492 (70.1%) patients were male, and the mean age was 66.6 years. During the mean follow-up period of 423 days, severe liver-irAEs (Common Terminology Criteria for Adverse Events grade ≥ 3) occurred in 43 patients. Patients were divided into five clusters (a, b, c, d, and e). The cumulative incidence of liver-irAE was higher in cluster c than in cluster a (hazard ratio [HR]: 13.59, 95% confidence interval [CI]: 1.70–108.76, P = 0.014), and overall survival was worse in clusters c and d than in cluster a (HR: 2.83, 95% CI: 1.77–4.50, P < 0.001; HR: 2.87, 95% CI: 1.47–5.60, P = 0.002, respectively). Clusters c and d were characterized by high temperature, C-reactive protein, platelets, and low albumin. However, there were differences in the prevalence of neutrophil count, neutrophil-to-lymphocyte ratio, and liver metastases between both clusters. Conclusions: The combined assessment of multiple markers and body temperature may help stratify high-risk groups for developing liver-irAE.

    DOI: 10.1111/jgh.16038

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  13. ANOREXIA IS ASSOCIATED WITH THE PRESENCE OF SARCOPENIA IN PATIENTS WITH CIRRHOSIS

    Ishizu Yoji, Yokoyama Shinya, Yamamoto Kenta, Ito Takanori, Imai Norihiro, Honda Takashi Honda, Ishigami Masatoshi, Kawashima Hiroki

    HEPATOLOGY   76 巻   頁: S1181 - S1181   2022年10月

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  14. USEFULNESS OF MUTATIONS INDUCED IN THE CORE REGION BY INTERFERON-BASED THERAPY

    Honda Takashi Honda, Ishigami Masatoshi, Kato Asuka, Yokoyama Shinya, Yamamoto Kenta, Ito Takanori, Imai Norihiro, Ishizu Yoji, Yasuda Satoshi, Toyoda Hidenori, Kumada Takashi, Ishikawa Tetsuya, Kawashima Hiroki

    HEPATOLOGY   76 巻   頁: S262 - S263   2022年10月

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  15. CLINICAL COURSE AND PROGNOSIS OF HEPATOCELLULAR CARCINOMA IN PATIENTS WITH HEMOPHILIA

    Imai Norihiro, Ishigami Masatoshi, Matsuda Noritaka, Yokoyama Shinya, Yamamoto Kenta, Ito Takanori, Ishizu Yoji, Honda Takashi Honda, Kawashima Hiroki

    HEPATOLOGY   76 巻   頁: S1330 - S1330   2022年10月

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  16. An improved method to assess skeletal muscle mass in patients with liver cirrhosis based on computed tomography images

    Sugiyama Yoshiaki, Ishizu Yoji, Ando Yusuke, Yokoyama Shinya, Yamamoto Kenta, Ito Takanori, Imai Norihiro, Nakamura Masanao, Honda Takashi, Kawashima Hiroki, Ishikawa Tetsuya, Ishigami Masatoshi

    HEPATOLOGY RESEARCH     2022年8月

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    記述言語:日本語  

    DOI: 10.1111/hepr.13820

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  17. Changes in Body Composition Predict the Time to Treatment Failure of Lenvatinib in Patients with Advanced Hepatocellular Carcinoma: A Pilot Retrospective Study

    Yamamoto Takafumi, Imai Norihiro, Kuzuya Teiji, Yokoyama Shinya, Yamamoto Kenta, Ito Takanori, Ishizu Yoji, Honda Takashi, Ishigami Masatoshi

    NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL   74 巻 ( 9 ) 頁: 3118 - 3127   2022年8月

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    記述言語:日本語   出版者・発行元:Nutrition and Cancer  

    Aim: Changes in body composition parameters are important prognostic factors in hepatocellular carcinoma (HCC) treatment. This study aimed to assess the clinical impact of early changes in body composition during lenvatinib (LEN) treatment on its time to treatment failure (TTF) for patients with advanced HCC. Methods: In this retrospective study, we enrolled 65 patients who were administered LEN as the first-line treatment for unresectable HCC and evaluated the body composition change using computed tomography. We focused on the body composition change after 2 weeks of LEN treatment and assessed its impact on TTF and prognosis. Results: Significant changes in body composition were observed during 14 weeks of LEN treatment. Among these changes, mean-skeletal muscle attenuation (SMA) decreased significantly within 2 weeks (P = 0.004) without symptoms or changes in the other parameters. In multivariate analysis, this early change in mean-SMA after LEN treatment was a significant predictor of time to treatment failure (HR: 2.67, 95%CI: 1.338–5.081, P = 0.005) in patients with HCC. Conclusions: This study revealed that LEN treatment induces a change in the skeletal muscle asymptomatically for a short period, and evaluation of this change may help to predict the TTF of LEN treatment in patients with HCC. Supplemental data for this article is available online at https://doi.org/10.1080/01635581.2022.2049322.

    DOI: 10.1080/01635581.2022.2049322

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  18. A case of anti-programmed death-ligand 1 antibody-induced multisystem immune-related adverse events with pancreatitis and steroid-resistant sclerosing cholangitis.

    Yamamoto T, Ito T, Mizuno K, Yokoyama S, Yamamoto K, Imai N, Ishizu Y, Honda T, Kawashima H, Matsui T, Hase T, Hashimoto N, Ishigami M

    Journal of digestive diseases     2022年8月

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    記述言語:英語  

    DOI: 10.1111/1751-2980.13122

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  19. Effectiveness of Porous Glass Membrane Pumping Emulsification Device in Transarterial Chemoembolization for Solitary Hepatocellular Carcinoma.

    Imai N, Ishigami M, Oie Y, Kumagai M, Inukai Y, Yokoyama S, Yamamoto K, Ito T, Ishizu Y, Honda T, Kawashima H

    Anticancer research   42 巻 ( 8 ) 頁: 3947 - 3951   2022年8月

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

    Background/Aim: A porous glass membrane-pumping emulsification device (GMD) enables the formation of a high-percentage water-in-oil emulsion with homogeneous and stable droplets. Although GMD is expected to improve the locoregional therapeutic effects of transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC), its effectiveness in the management of solitary HCC remains unclear. Patients and Methods: Patients treated for solitary HCCs (<5 cm) were retrospectively reviewed. A total of 46 patients who could not undergo liver resection and were unsuitable for radiofrequency ablation were included in this study. Among these, 22 patients underwent TACE using a GMD (GMD-TACE group) and 24 underwent stereotactic body radiotherapy (SBRT) using a robotic radiosurgery system (SBRT group). Local control rates were compared between the two groups. Results: The median HCC tumour size was 24 mm (range=12-50 mm) and 22 mm (range=8-39 mm) in the GMD-TACE and SBRT groups, respectively; however, the difference between the groups was not significant. Age, liver function test results, or Child-Pugh scores were not significantly different between the two groups. The rate of local control at 6 months after treatment was 100% in both groups. Although the 1-year local control rate was higher in the SBRT group (92.3%) than in the GMD-TACE group (81.8%), there was no significant difference in the log-rank test (p=0.654). No major treatment-related complications occurred in either group during the observation period. Conclusion: TACE with GMD could be considered an effective treatment option for the management of solitary HCC.

    DOI: 10.21873/anticanres.15889

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  20. Factors associated with the progression of myosteatosis in patients with cirrhosis.

    Ishizu Y, Ishigami M, Honda T, Imai N, Ito T, Yamamoto K, Yokoyama S, Ishikawa T, Fujishiro M

    Nutrition (Burbank, Los Angeles County, Calif.)   103-104 巻   頁: 111777   2022年6月

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    記述言語:英語  

    DOI: 10.1016/j.nut.2022.111777

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  21. Pipeline Esophagogastric Varices Secondary to Extrahepatic Portal Vein Obstruction Treated Endoscopically with the Assistance of Transileocolic Obliteration: A Case Report.

    Yokoyama S, Ishizu Y, Honda T, Imai N, Ito T, Yamamoto K, Komada T, Hayashi M, Ishigami M

    Internal medicine (Tokyo, Japan)   advpub 巻 ( 0 )   2022年4月

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    記述言語:英語   出版者・発行元:一般社団法人 日本内科学会  

    DOI: 10.2169/internalmedicine.9404-22

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  22. Astaxanthin Attenuates Nonalcoholic Steatohepatitis with Downregulation of Osteoprotegerin in Ovariectomized Mice Fed Choline-Deficient High-Fat Diet

    Zhao Meng, Ma Lingyun, Honda Takashi, Kato Asuka, Ohshiro Taichi, Yokoyama Shinya, Yamamoto Kenta, Ito Takanori, Imai Norihiro, Ishizu Yoji, Nakamura Masanao, Kawashima Hiroki, Tsuji Noriko M., Ishigami Masatoshi, Fujishiro Mitsuhiro

    DIGESTIVE DISEASES AND SCIENCES     2022年4月

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    記述言語:日本語   出版者・発行元:Digestive Diseases and Sciences  

    Background: Postmenopausal estrogen decline increases the risk of developing nonalcoholic steatohepatitis (NASH), and it might accelerate progression to cirrhosis and hepatocellular carcinoma. Aims: This study aimed to investigate a novel therapy for postmenopausal women who are diagnosed with NASH. Methods: Seven-week-old female C57BL/6 J mice were divided into three experimental groups as follows: (1) sham operation (SHAM group), (2) ovariectomy (OVX group), and (3) ovariectomy + 0.02% astaxanthin (OVX + ASTX group). These three groups of mice were fed a choline-deficient high-fat (CDHF) diet for 8 weeks. Blood serum and liver tissues were collected to examine liver injury, histological changes, and hepatic genes associated with NASH. An in vitro study was performed with the hepatic stellate cell line LX-2. Results: The administration of ASTX significantly improved pathological NASH with suppressed steatosis, inflammation, and fibrosis, in comparison with those in the OVX-induced estrogen deficiency group. As a result, liver injury was also attenuated with reduced levels of alanine aminotransferase and aspartate transaminase. In addition, our study found that ASTX supplementation decreased hepatic osteoprotegerin (OPG) in vivo, a possible factor that contributes to NASH development. In vitro, this study further confirmed that ASTX has an inhibitory effect on the secretion of OPG in LX-2 human hepatic stellate cells. Conclusions: Our findings suggest that ASTX alleviates CDHF-OVX-induced pathohistological NASH with downregulated OPG, possibly via suppression of the transforming growth factor beta pathway. ASTX could has promise for use in postmenopausal women diagnosed with NASH. Graphical Abstract: [Figure not available: see fulltext.]

    DOI: 10.1007/s10620-022-07489-6

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  23. Absence of large portal collateral vessels is associated with spontaneous improvement of cirrhotic portal vein thrombosis

    Yokoyama Shinya, Ishizu Yoji, Honda Takashi, Imai Norihiro, Ito Takanori, Yamamoto Kenta, Tsuzuki Tomoyuki, Ishigami Masatoshi

    HEPATOLOGY RESEARCH   52 巻 ( 2 ) 頁: 199 - 209   2022年2月

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    記述言語:日本語   出版者・発行元:Hepatology Research  

    Aim: Portal vein thrombosis (PVT) is a major complication in patients with liver cirrhosis (LC). In some cases, PVT decreases spontaneously, but the factors that predict this are still not fully understood. Methods: This was a retrospective, multicenter study that included 77 consecutive patients with cirrhotic PVT. Forty-eight patients did not undergo anticoagulation and 29 patients did between the time of the first diagnosis of PVT and the follow-up radiological imaging undertaken 1–6 months later. A complete disappearance and 25% shrinkage of PVT was defined as complete remission (CR) and partial remission (PR), respectively. Portosystemic collateral vessels larger than 9 mm in diameter were defined as large collateral vessels. Results: Complete remission + PR was found in 37.5% of the anticoagulation-naïve patients. On univariate analysis, the absence of large collateral vessels, absence of PVT in the main trunk of the portal vein, a high platelet count, and a low FIB-4 index were significant factors associated with CR + PR. On multivariate analysis, the absence of large collateral vessels was the unique factor associated with CR + PR of PVT (odds ratio 5.9; 95% confidence interval, 1.73–20.1). The CR + PR rate for anticoagulated patients was 44.8%. However, no predictors for a good treatment effect of anticoagulation for PVT were identified. Conclusions: Spontaneous improvement of PVT in patients with LC can be expected when large collateral vessels are absent. For these patients, the option of observing them without anticoagulation can be considered in expectation of spontaneous reduction of PVT.

    DOI: 10.1111/hepr.13725

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  24. Decreased appetite is associated with the presence of sarcopenia in patients with cirrhosis

    Ishizu Yoji, Ishigami Masatoshi, Honda Takashi, Imai Norihiro, Ito Takanori, Yamamoto Kenta, Yokoyama Shinya, Ishikawa Tetsuya, Kawashima Hiroki

    NUTRITION   103 巻   頁: 111807   2022年

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    記述言語:英語   出版者・発行元:Nutrition  

    Objectives: To our knowledge, the relationship between appetite and sarcopenia in patients with cirrhosis is unknown. The aims of this study were to examine the factors associated with decreased appetite and to clarify the relationship between appetite and sarcopenia. Methods: This study included 61 patients with cirrhosis. The patients were asked to describe their appetite using a numerical rating scale (NRS) from 0 (none at all) to 10 (most), with ≤5 defined as decreased appetite. The clinical characteristics, gastrointestinal symptoms as assessed using the Gastrointestinal Symptom Rating Scale, handgrip strength, and skeletal muscle area at the third vertebra were collected retrospectively. Sarcopenia was diagnosed according to the criteria of the Japan Society of Hepatology. The differences in these factors between patients with and without decreased appetite, and the factors associated with the presence of sarcopenia were examined. Results: Alcoholic liver disease was the most common etiology. The median Model for End-Stage Liver Disease score was 8 (interquartile range = 7 - 10) and hepatocellular carcinoma was present in 35 patients. Overall, 36% of the patients with cirrhosis had decreased appetite. Patients with decreased appetite had a higher frequency of abdominal pain and acid reflux–related symptoms and significantly lower handgrip strength than patients without, among both men (P = 0.034) and women (P = 0.017). The multivariate analysis identified a decrease in appetite as a significant factor associated with the presence of sarcopenia (NRS one increase, odds ratio, 0.701; 95% confidence interval, 0.502–0.977; P = 0.036). Conclusion: Decreased appetite was associated with the presence of sarcopenia.

    DOI: 10.1016/j.nut.2022.111807

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  25. Assessing the Complicated Venous Hemodynamics and Therapeutic Outcomes of Budd-Chiari Syndrome with Respiratory-gated 4D Flow MR Imaging During the Expiratory and Inspiratory Phases.

    Hyodo R, Takehara Y, Mizuno T, Ichikawa K, Yokoyama S, Ishizu Y, Naganawa S

    Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine   advpub 巻 ( 0 )   2021年12月

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    記述言語:英語   出版者・発行元:日本磁気共鳴医学会  

    DOI: 10.2463/mrms.ici.2021-0110

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  26. Obesity and myosteatosis: the two characteristics of dynapenia in patients with cirrhosis

    Sugiyama Yoshiaki, Ishizu Yoji, Ando Yusuke, Yokoyama Shinya, Yamamoto Kenta, Ito Takanori, Imai Norihiro, Nakamura Masanao, Honda Takashi, Kawashima Hiroki, Ishikawa Tetsuya, Ishigami Masatoshi

    EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY   33 巻 ( 1S Suppl 1 ) 頁: E916 - E921   2021年12月

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    記述言語:日本語   出版者・発行元:European journal of gastroenterology &amp; hepatology  

    OBJECTIVE: In patients with liver cirrhosis, the clinical characteristics of dynapenia, a condition in which skeletal muscle mass is maintained but muscle strength is reduced, are not yet known. This study aimed to clarify the characteristics of dynapenia and its impact on quality of life (QOL) in patients with liver cirrhosis. METHODS: We retrospectively analyzed 116 patients with cirrhosis. Based on grip strength and skeletal muscle mass measured by the bioelectrical impedance analysis method, patients were divided into four groups: normal muscle status, dynapenia, pre-sarcopenia (a condition involving only low muscle mass), and sarcopenia. The characteristics of dynapenia and its influence on QOL were examined. RESULTS: Fourteen patients had dynapenia. Liver function did not differ among the four groups. In patients with dynapenia, BMI was highest and computed tomography attenuation of skeletal muscle at the third lumbar spine vertebra was lowest among the four groups. The percentage of patients with both BMI ≥25 kg/m2 and myosteatosis was significantly higher in patients with dynapenia [9/14 (64.3%)] than in those with sarcopenia [2/23 (8.7%), P = 0.004] and pre-sarcopenia [0/18 (0%), P < 0.001] and tended to be higher than those with normal muscle status [16/61 (26.2%), P = 0.065]. The physical QOL in patients with dynapenia was as low as that in those with sarcopenia and significantly lower than that in those with normal muscle status. CONCLUSION: Cirrhotic patients with dynapenia had high BMI and myosteatosis, and impaired physical QOL.

    DOI: 10.1097/MEG.0000000000002303

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  27. Safety and Efficacy of Glass Membrane Pumping Emulsification Device in Transarterial Chemoembolization for Hepatocellular Carcinoma: First Clinical Outcomes

    Imai Norihiro, Yokoyama Shinya, Yamamoto Kenta, Ito Takanori, Ishizu Yoji, Honda Takashi, Ishigami Masatoshi

    ANTICANCER RESEARCH   41 巻 ( 11 ) 頁: 5817 - 5820   2021年11月

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    記述言語:日本語   出版者・発行元:Anticancer Research  

    Aim: Novel glass membrane pumping emulsification devices (GMDs) enable the formation of a high-percentage water-in-oil emulsion with homogeneous and stable droplets. Although GMDs are expected to improve therapeutic effects in transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC), clinical outcomes are not yet available. Patients and Methods: A total of 26 patients with unresectable HCC who underwent TACE using a GMD were analyzed retrospectively. Ethiodized oil was mixed with epirubicin solution using a GMD. The emulsion was injected into the tumor-feeding artery, followed by embolization. Results: The median size of HCCs was 28 (range=15-60) mm, and 15 nodules were solitary. Overall treatment effects were complete response in 18 cases (90%) and partial response in two (10%). The local recurrence rate at 6 months was 24.2%. No major complication was observed except for grade 4 elevations of liver enzymes in one case. Conclusion: TACE using a GMD is effective and safe in clinical practice.

    DOI: 10.21873/anticanres.15399

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  28. Microbiome, fibrosis and tumor networks in a non-alcoholic steatohepatitis model of a choline-deficient high-fat diet using diethylnitrosamine

    Yamamoto Kenta, Honda Takashi, Yokoyama Shinya, Ma Lingyun, Kato Asuka, Ito Takanori, Ishizu Yoji, Kuzuya Teiji, Nakamura Masanao, Kawashima Hiroki, Ishigami Masatoshi, Tsuji Noriko M., Fujishiro Mitsuhiro

    DIGESTIVE AND LIVER DISEASE   53 巻 ( 11 ) 頁: 1443 - 1450   2021年11月

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    記述言語:日本語   出版者・発行元:Digestive and Liver Disease  

    Background & aims: Hepatocellular carcinoma in nonalcoholic steatohepatitis is caused by the complex factors of inflammation, fibrosis and microbiomes. We used network analysis to examine the interrelationships of these factors. Methods: C57Bl/6 mice were categorized into groups: choline-sufficient high-fat (CSHF, n = 8), choline-deficient high-fat (CDHF, n = 9), and CDHF+ diethylnitrosamine (DEN, n = 8). All mice were fed CSHF or CDHF for 20 weeks starting at week 8, and mice in the CDHF + DEN group received one injection of DEN at 3 weeks of age. Bacterial gene was isolated from feces and analyzed using Miseq. Results: The CSHF group had less fibrosis than the other groups. Tumors were found in 22.2% and 87.5% of the CDHF group and CDHF + DEN groups, respectively. Gene expression in the liver of Cdkn1a (p21: tumor-suppressor) and c-jun was highest in the CDHF group. Bacteroides, Roseburia, Odoribacter, and Clostridium correlated with fibrosis. Streptococcus and Dorea correlated with inflammation and tumors. Akkermansia and Bilophila were inversely correlated with fibrosis and Bifidobacterium was inversely correlated with tumors. Conclusions: DEN suppressed the overexpression of p21 caused by CDHF. Some bacteria formed a relationship networking associated with their progression and inhibition for tumors and fibrosis.

    DOI: 10.1016/j.dld.2021.02.013

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  29. Factors associated with bleeding after endoscopic variceal ligation in children

    Yokoyama Shinya, Ishizu Yoji, Ishigami Masatoshi, Honda Takashi, Kuzuya Teiji, Ito Takanori, Hinoki Akinari, Sumida Wataru, Shirota Chiyoe, Tainaka Takahisa, Makita Satoshi, Yokota Kazuki, Uchida Hiroo, Fujishiro Mitsuhiro

    PEDIATRICS INTERNATIONAL   63 巻 ( 10 ) 頁: 1223 - 1229   2021年10月

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    記述言語:日本語   出版者・発行元:Pediatrics International  

    Background: Endoscopic variceal ligation (EVL) is a widely accepted treatment for esophagogastric varices in patients with portal hypertension (PHT). It is used for urgent treatment and prophylactic treatment of esophagogastric varices in pediatric as well as adult patients. However, major life-threatening adverse events such as early rebleeding can occur. Although early rebleeding after EVL among children and adolescents has been reported, the risk factors remain obscure. This study evaluated the risk factors for early rebleeding after EVL in children and adolescents. Methods: The subjects were children and adolescents (<18 years) with PHT who underwent EVL for esophagogastric varices. Early rebleeding was defined as hematemesis, active bleeding, or blood retention in the stomach, confirmed by esophagogastroduodenoscopy from 2 h to 5 days after EVL. Results: A total of 50 EVL sessions on 22 patients were eligible for this study. There were four episodes of early rebleeding. No other major adverse event has occurred. Multivariate analysis showed that EVL implemented at cardiac varices just below the esophagogastric junction (EGJ), within 5 mm from the EGJ, is the independent factor for a higher risk of early rebleeding: odds ratio 18.2 (95% confidence interval: 1.40–237.0), P = 0.02. Conclusions: Children and adolescents who undergo EVL for cardiac varices just below the EGJ have a higher risk of early rebleeding than those who do not.

    DOI: 10.1111/ped.14614

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  30. Conditioned medium from stem cells derived from human exfoliated deciduous teeth ameliorates NASH via the Gut-Liver axis

    Muto Hisanori, Ito Takanori, Tanaka Taku, Yokoyama Shinya, Yamamoto Kenta, Imai Norihiro, Ishizu Yoji, Maeda Keiko, Honda Takashi, Ishikawa Tetsuya, Kato Asuka, Ohshiro Taichi, Kano Fumiya, Yamamoto Akihito, Sakai Kiyoshi, Hibi Hideharu, Ishigami Masatoshi, Fujishiro Mitsuhiro

    SCIENTIFIC REPORTS   11 巻 ( 1 ) 頁: 18778   2021年9月

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    記述言語:日本語   出版者・発行元:Scientific Reports  

    Non-alcoholic steatohepatitis (NASH) occurrence has been increasing and is becoming a major cause of liver cirrhosis and liver cancer. However, effective treatments for NASH are still lacking. We examined the benefits of serum-free conditioned medium from stem cells derived from human exfoliated deciduous teeth (SHED-CM) on a murine non-alcoholic steatohepatitis (NASH) model induced by a combination of Western diet (WD) and repeated administration of low doses of carbon tetrachloride intraperitoneally, focusing on the gut-liver axis. We showed that repeated intravenous administration of SHED-CM significantly ameliorated histological liver fibrosis and inflammation in a murine NASH model. SHED-CM inhibited parenchymal cell apoptosis and reduced the activation of inflammatory macrophages. Gene expression of pro-inflammatory and pro-fibrotic mediators (such as Tnf-α, Tgf-β, and Ccl-2) in the liver was reduced in mice treated with SHED-CM. Furthermore, SHED-CM protected intestinal tight junctions and maintained intestinal barrier function, while suppressing gene expression of the receptor for endotoxin, Toll-like receptor 4, in the liver. SHED-CM promoted the recovery of Caco-2 monolayer dysfunction induced by IFN-γ and TNF-α in vitro. Our findings suggest that SHED-CM may inhibit NASH fibrosis via the gut-liver axis, in addition to its protective effect on hepatocytes and the induction of macrophages with unique anti-inflammatory phenotypes.

    DOI: 10.1038/s41598-021-98254-8

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  31. Successful repeated endoscopic injection sclerotherapy for severe esophagogastric varices in an infant with biliary atresia: A case report

    Yokoyama S., Honda T., Kuzuya T., Ishizu Y., Ito T., Yamamoto K., Tanaka T., Muto H., Sugiyama Y., Fujishiro M.

    Gastroenterological Endoscopy   62 巻 ( 12 ) 頁: 3064 - 3071   2020年12月

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    記述言語:日本語   出版者・発行元:Gastroenterological Endoscopy  

    A 10-month-old boy with biliary atresia who had undergone the Kasai procedure, was admitted to our hospital due to tarry stool. We performed emergency esophagogastroduodenoscopy and found severe esophagogastric varices. There was a spurting bleeding site at the lower esophagus. We implemented endoscopic injection sclerotherapy (EIS) for esophagogastric variceal bleeding, since it was impossible to insert the scope through the esophagus with an endoscopic variceal ligation device attached. After performing four sessions of EIS, the patient developed esophageal ulcers and stricture related to EIS, leading to poor oral intake and body weight loss. We were able to manage these adverse events with conservative treatment. After healing of the esophageal ulcers and stricture, two additional sessions of EIS were performed. The patient's esophagogastric varices disappeared completely. Intra-variceal EIS followed by para-variceal EIS by polidocanol was reported to be effective and relatively safe for the treatment of esophageal varices in adult patients. The aim of paravariceal EIS is to form ulcers at the injection sites, resulting in the development of fibrosis of the mucosa during the healing process. This mucosal fibrosis is considered important for preventing recurrence of varices. There is little evidence for the safety and efficacy of intra-variceal EIS followed by para-variceal EIS in pediatric patients. Although we should be cautious of EIS-related stricture due to esophageal ulcer, especially in children who have a narrower esophageal lumen than adults, we have experienced a successful case of EIS for esophageal varices in an infant with biliary atresia.

    DOI: 10.11280/gee.62.3064

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  32. Spleen stiffness by 2-D shear wave elastography is the most accurate predictor of high-risk esophagogastric varices in children with biliary atresia

    Yokoyama Shinya, Ishigami Masatoshi, Honda Takashi, Kuzuya Teiji, Ishizu Yoji, Ito Takanori, Hirooka Yoshiki, Tanaka Yujiro, Tainaka Takahisa, Shirota Chiyoe, Chiba Kosuke, Uchida Hiroo, Fujishiro Mitsuhiro

    HEPATOLOGY RESEARCH   49 巻 ( 10 ) 頁: 1162 - 1168   2019年10月

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    記述言語:日本語   出版者・発行元:Hepatology Research  

    Aim: Esophagogastric variceal hemorrhage is a cause of poor prognosis in patients with biliary atresia (BA). To prevent variceal hemorrhage, simple and reliable screening methods for high-risk esophagogastric varices (HR-EGV) are needed. We evaluated the efficacy of liver stiffness (LS) and spleen stiffness (SS) as measured by 2-D shear wave elastography (2D-SWE), which was reported to be more accurate than transient elastography, for detecting HR-EGV in children with BA. Methods: Thirty-four children with BA were enrolled. Both LS and SS were measured by 2D-SWE. The presence of large esophageal varices or esophageal varices of any size with red wale marking and/or the presence of gastric varices along the cardia were defined as HR-EGV. Clinical data were collected and previously reported prediction indices for varices were calculated. Results: Liver stiffness and SS were obtained from all patients. Fourteen patients showed HR-EGV. Significantly different variables between patients with and without HR-EGV were as follows: spleen diameter (116 mm vs. 95 mm), clinical prediction rule (104.7 vs. 124.7), King's variceal prediction score (78.8 vs. 99.4), aspartic aminotransferase-to-platelet ratio index (2.03 vs. 0.98), LS (2.63 m/s vs. 1.87 m/s), and SS (4.44 m/s vs. 3.69 m/s). The highest area under the receiver operating characteristic curve for detecting HR-EGV was that for SS (0.900), and the cut-off SS of 4.12 m/s yielded 92.9% sensitivity and 90% specificity. The intraclass correlation coefficient for intra-observer reproducibility was 0.828. Conclusions: Spleen stiffness from 2D-SWE offered the most accurate predictor of HR-EGV in BA children.

    DOI: 10.1111/hepr.13381

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  33. Antifibrotic Effects of 1,25(OH)(2)D-3 on Nonalcoholic Steatohepatitis in Female Mice

    Ma Lingyun, Ishigami Masatoshi, Honda Takashi, Yokoyama Shinya, Yamamoto Kenta, Ishizu Yoji, Kuzuya Teiji, Hayashi Kazuhiko, Hirooka Yoshiki, Goto Hidemi

    DIGESTIVE DISEASES AND SCIENCES   64 巻 ( 9 ) 頁: 2581 - 2590   2019年9月

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    記述言語:日本語   出版者・発行元:Digestive Diseases and Sciences  

    Background: Postmenopausal women have a higher risk of nonalcoholic steatohepatitis (NASH) along with an increase in age, and vitamin D deficiency occurs in some patients with NASH. Aim: We performed ovariectomy (OVX) surgery on female mice to mimic menopause, fed them a choline-deficient high-fat (CDHF) diet to induce NASH, and then investigated the effects of treatment with 1,25(OH)2D3. Methods: Seven-week-old C57BL/6J female mice were separated into five experimental groups: SHAM, OVX, and OVX + intraperitoneal (i.p.) injection of 1,25(OH)2D3 (0.0008, 0.004, and 0.02 μg/kg). All groups were fed a CDHF diet for 8 weeks. Injections took place twice per week throughout the experimental period. Blood samples and liver tissue were collected for analyzing liver histological changes, serum biochemical indicators of hepatic function, and hepatic genes associated with fibrosis. Results: Supplementation of 1,25(OH)2D3 in CDHF-diet mice showed decreased serum levels of ALT, AST, indicating the improvement in overall liver function, and suppressed histological NASH regarding fibrosis stage, lobular inflammation, and steatosis compared to the OVX group. Primary fibrotic markers of TGF-β, TIMP-1, α-SMA, and COL1A1 were significantly lower in the 1,25(OH)2D3 groups than in the OVX group. Furthermore, down-regulated levels of SMAD2 and SMAD3 were also observed in 1,25(OH)2D3 groups. Conclusion: Supplementation of 1,25(OH)2D3 may ameliorate liver fibrosis and improve liver function in OVX mice with NASH induced by a CDHF diet, suggesting the therapeutic effects on postmenopause with NASH.

    DOI: 10.1007/s10620-019-05560-3

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  34. NON-INVASIVE SCREENING FOR DETECTING ESOPHAGOGASTRIC VARICES IN CHILDREN WITH BILIARY ATRESIA

    Yokoyama Shinya, Ishigami Masatoshi, Honda Takashi, Kuzuya Teiji, Ishizu Yoji, Ito Takanori, Shirota Chiyoe, Uchida Hiroo, Fujishiro Mitsuhiro

    HEPATOLOGY   70 巻   頁: 200A - 200A   2019年10月

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講演・口頭発表等 1

  1. 門脈側副血行路の発達の有無は肝硬変による門脈血栓症の自然経過に影響する

    横山 晋也, 石津 洋二, 石上 雅敏

    日本消化器病学会総会 

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    開催年月日: 2022年4月

    会議種別:シンポジウム・ワークショップ パネル(公募)