2022/03/23 更新

写真a

イトウ タカノリ
伊藤 隆徳
ITO Takanori
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) ( 2018年3月   名古屋大学 ) 

研究キーワード 5

  1. 脂肪肝

  2. 肝再生

  3. 自己免疫性肝疾患

  4. 肝疾患

  5. 免疫チェックポイント阻害薬

研究分野 1

  1. ライフサイエンス / 消化器内科学

所属学協会 7

  1. 日本内科学会   総合内科専門医

  2. 日本消化器病学会   専門医

  3. 日本肝臓学会   指導医

  4. 日本消化器内視鏡学会   専門医

  5. 日本超音波医学会

  6. 日本炎症・再生医学会

  7. 日本再生医療学会

▼全件表示

受賞 7

  1. JDDW2021若手奨励賞

    2021年11月  

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    受賞区分:国内学会・会議・シンポジウム等の賞 

  2. Taisho-Toyama Award

    2018年  

  3. 名古屋大学大学院医学系研究科病態内科学講座研究発表会受賞(第27回)

    2017年  

  4. American Association for the Study of Liver Diseases (AASLD) Basic Science Young Investigator Awards (YIA) (Boston)

    2016年  

  5. American Association for the Study of Liver Diseases (AASLD) presidential poster of distinction (Boston)

    2016年  

  6. 第134回 名古屋肝疾患研究会 優秀演題賞

    2015年  

  7. American Association for the Study of Liver Diseases (AASLD) poster of distinction (Washington, D.C.)

    2013年  

▼全件表示

 

論文 100

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

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

    Nutrition and cancer     頁: 1 - 10   2022年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1080/01635581.2022.2049322

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  2. Patients with low muscle mass have characteristic microbiome with low potential for amino acid synthesis in chronic liver disease.

    Yamamoto K, Ishizu Y, Honda T, Ito T, Imai N, Nakamura M, Kawashima H, Kitaura Y, Ishigami M, Fujishiro M

    Scientific reports   12 巻 ( 1 ) 頁: 3674   2022年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Scientific Reports  

    Sarcopenia is thought to be related to the microbiome, but not enough reports in chronic liver disease (CLD) patients. In addition to the differences in microbiome, the role of the microbiome in the gut is also important to be clarified because it has recently been shown that the microbiome may produce branched-chain amino acids (BCAAs) in the body. In this single-center study, sixty-nine CLD patients were divided by skeletal muscle mass index (SMI) into low (L-SMI: n = 25) and normal (N-SMI: n = 44). Microbiome was analyzed from stool samples based on V3-4 region of bacterial 16S rRNA). L-SMI had a lower Firmicutes/Bacteroidetes ratio than N-SMI. At the genus level, Coprobacillus, Catenibacterium and Clostridium were also lower while the Bacteroides was higher. Predictive functional profiling of the L-SMI group showed that genes related to nitrogen metabolism were enriched, but those related to amino acid metabolism, including BCAA biosynthesis, were lower. The genes related to 'LPS biosynthesis' was also higher. The microbiome of CLD patients with low muscle mass is characterized not only by high relative abundance of gram-negative bacteria with LPS, but also by the possibility of low potential for amino acid synthesis including BCAAs.

    DOI: 10.1038/s41598-022-07810-3

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  3. Immune-related Liver Injury is a Poor Prognostic Factor in Patients with Nonsmall Cell Lung Cancer Treated with Immune Checkpoint Inhibitors.

    Yamamoto T, Ito T, Hase T, Ishigami M, Mizuno K, Yamamoto K, Imai N, Ishizu Y, Honda T, Shibata H, Hatta T, Yogo N, Yasuda S, Toyoda H, Abe T, Kawashima H, Hashimoto N, Fujishiro M

    Cancer investigation   40 巻 ( 2 ) 頁: 189 - 198   2022年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Cancer Investigation  

    It remains unclear whether severe liver immune-related adverse events (liver-irAEs) can affect the prognosis in nonsmall cell lung carcinoma (NSCLC) patients. Of the 365 NSCLC patients treated with immune checkpoint inhibitors (ICIs), 19 suffered from severe liver-irAEs (grade ≥3). The median time-to-onset of liver-irAEs was 53 days postinjection of the first ICI. The progression-free survival and overall survival of the liver-irAEs group (median 69 and 262 days, respectively) were significantly worse than the nonliver-irAEs group (128 and 722 days; P = 0.010 and P = 0.007; respectively). In conclusion, liver-irAEs were associated with poor prognosis in NSCLC patients.

    DOI: 10.1080/07357907.2021.1994586

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

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

    Hepatology research : the official journal of the Japan Society of Hepatology   52 巻 ( 2 ) 頁: 199 - 209   2022年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   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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  5. The influence of hepatitis C virus eradication on hepatocarcinogenesis in patients with hemophilia.

    Inukai Y, Imai N, Yamamoto K, Ito T, Ishizu Y, Honda T, Okamoto S, Kanematsu T, Suzuki N, Matsushita T, Ishigami M, Fujishiro M

    Annals of hepatology   27 巻 ( 1 ) 頁: 100545   2022年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Annals of Hepatology  

    Introduction and objectives: Hepatitis C virus (HCV) infections in patients with hemophilia lead to the development of hepatocellular carcinoma (HCC) at a relatively younger age than that in patients without hemophilia. Although recent progress in direct-acting-antivirals has facilitated a high rate of sustained virological response (SVR), the clinical influence of HCV eradication in hemophilia patients remains unclear. This study aimed to compare the clinical outcomes of SVR against HCV in patients with and without hemophilia. Patients and methods: The study enrolled 699 patients who achieved SVR after HCV antiviral treatment. Patients were divided into two groups: 78 patients with hemophilia (H group) and 621 patients without hemophilia (NH group). We evaluated patient characteristics, clinical outcomes, and the cumulative incidence of HCC after SVR. Results: Compared with the NH group, patients in the H-group were significantly younger and had a lower hepatic fibrosis score. No difference was found in the incidence of liver-related disease or overall death between the two groups over a mean follow-up period of 7 years. Four patients in the H group and 36 patients in the NH group were diagnosed with HCC after SVR. Multivariate analysis showed that male sex, age, and cirrhosis were significant risk factors for HCC incidence. There was no significant difference in the cumulative incidence of HCC after propensity-score matching adjusting for the risk factors of HCC between the two groups. Conclusion: Hemophilia is not a significant risk factor for hepatocarcinogenesis after SVR against HCV.

    DOI: 10.1016/j.aohep.2021.100545

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  6. Mortality of inactive hepatitis B virus carriers in Japan is similar to that of the general population.

    Kumada T, Toyoda H, Yasuda S, Ito T, Tanaka J

    Hepatology research : the official journal of the Japan Society of Hepatology   52 巻 ( 1 ) 頁: 81 - 92   2022年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Hepatology Research  

    Aims: Data on the long-term outcomes of individuals with hepatitis B virus (HBV) infection who are hepatitis envelope antigen (HBeAg)-negative inactive carriers (ICs) are limited due to small numbers. We compared the long-term prognosis of well-defined ICs with that of age- and gender-matched general population controls. Methods: A total of 526 HBeAg-negative patients who demonstrated alanine aminotransferase (ALT) level ≤40 U/L and HBV DNA level ≤4.3 log IU/ml at least three times within 1 year after the start of follow-up were enrolled as ICs. Inactive carriers were divided into two groups: Group A (n = 332), whose ALT level was ≤30 U/L and HBV DNA level was ≤3.3 log IU/ml, and Group B (remaining patients, n = 194). We determined the long-term prognosis of ICs and compared it with that of general population controls. We also analyzed factors associated with hepatitis B surface antigen (HBsAg) clearance and phase transition in ICs. Results: There were no significant differences in hepatocellular carcinoma development or all-cause, liver-related, or non–liver-related mortality between Groups A and B. There was no significant difference in all-cause mortality between ICs and the general population. Low HBsAg level (≤3.0 log IU/ml) and the presence of fatty liver were associated with HBsAg clearance and high alpha-fetoprotein level was associated with phase transition. Conclusions: The long-term prognosis of well-defined ICs was similar to that of general population controls. In addition, the ICs had a high HBsAg clearance rate and low phase transition rate.

    DOI: 10.1111/hepr.13723

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  7. Environmental factors, medical and family history, and comorbidities associated with primary biliary cholangitis in Japan: a multicenter case-control study.

    Matsumoto K, Ohfuji S, Abe M, Komori A, Takahashi A, Fujii H, Kawata K, Noritake H, Tadokoro T, Honda A, Asami M, Namisaki T, Ueno M, Sato K, Kakisaka K, Arakawa M, Ito T, Tanaka K, Matsui T, Setsu T, Takamura M, Yasuda S, Katsumi T, Itakura J, Sano T, Tamura Y, Miura R, Arizumi T, Asaoka Y, Uno K, Nishitani A, Ueno Y, Terai S, Takikawa Y, Morimoto Y, Yoshiji H, Mochida S, Ikegami T, Masaki T, Kawada N, Ohira H, Tanaka A

    Journal of gastroenterology   57 巻 ( 1 ) 頁: 19 - 29   2022年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Journal of Gastroenterology  

    Background: Primary biliary cholangitis (PBC) is considered to be caused by the interaction between genetic background and environmental triggers. Previous case–control studies have indicated the associations of environmental factors (tobacco smoking, a history of urinary tract infection, and hair dye) use with PBC. Therefore, we conducted a multicenter case–control study to identify the environmental factors associated with the development of PBC in Japan. Methods: From 21 participating centers in Japan, we prospectively enrolled 548 patients with PBC (male/female = 78/470, median age 66), and 548 age- and sex-matched controls. These participants completed a questionnaire comprising 121 items with respect to demographic, anthropometric, socioeconomic features, lifestyle, medical/familial history, and reproductive history in female individuals. The association was determined using conditional multivariate logistic regression analysis. Results: The identified factors were vault toilet at home in childhood [odds ratio (OR), 1.63; 95% confidence interval (CI), 1.01–2.62], unpaved roads around the house in childhood (OR, 1.43; 95% CI, 1.07–1.92), ever smoking (OR, 1.70; 95% CI, 1.28–2.25), and hair dye use (OR, 1.57; 95% CI, 1.15–2.14) in the model for lifestyle factors, and a history of any type of autoimmune disease (OR, 8.74; 95% CI, 3.99–19.13), a history of Cesarean section (OR, 0.20; 95% CI, 0.077–0.53), and presence of PBC in first-degree relatives (OR, 21.1; 95% CI, 6.52–68.0) in the model for medical and familial factors. Conclusions: These results suggest that poor environmental hygiene in childhood (vault toilets and unpaved roads) and chronic exposure to chemicals (smoking and hair dye use) are likely to be risk factors for the development of PBC in Japan.

    DOI: 10.1007/s00535-021-01836-6

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  8. Changes in the gut microbiota after hepatitis C virus eradication.

    Honda T, Ishigami M, Yamamoto K, Takeyama T, Ito T, Ishizu Y, Kuzuya T, Nakamura M, Kawashima H, Miyahara R, Ishikawa T, Hirooka Y, Fujishiro M

    Scientific reports   11 巻 ( 1 ) 頁: 23568   2021年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Scientific Reports  

    The gut microbiota interacts with infectious diseases and affects host immunity. Liver disease is also reportedly associated with changes in the gut microbiota. To elucidate the changes in the gut microbiota before and after hepatitis C virus (HCV) eradication through direct-acting antiviral (DAA) treatment in patients with chronic hepatitis C (CHC), we investigated 42 samples from 14 patients who received DAA therapy for HCV. Fecal samples were obtained before treatment (Pre), when treatment ended (EOT), and 24 weeks after treatment ended (Post24). The target V3–4 region of the 16S rRNA gene from fecal samples was amplified using the Illumina Miseq sequencing platform. The diversity of the gut microbiota did not significantly differ between Pre, EOT, and Post24. Principal coordinates analysis showed that for each patient, the values at Pre, EOT, and Post24 were concentrated within a small area. The linear discriminant analysis of effect size showed that the relative abundances of Faecalibacterium and Bacillus increased at EOT, further increased at Post24, and were significantly increased at Post24 compared to Pre. These suggest that changes in the gut microbiota should be considered as among the various effects observed on living organisms after HCV eradication.

    DOI: 10.1038/s41598-021-03009-0

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  9. Impact of switching to tenofovir alafenamide fumarate in patients with entecavir-treated chronic hepatitis B.

    Kumada T, Toyoda H, Yasuda S, Ito T, Tanaka J

    European journal of gastroenterology & hepatology   33 巻 ( 1S Suppl 1 ) 頁: e898 - e904   2021年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:European journal of gastroenterology & hepatology  

    BACKGROUND AND AIMS: Tenofovir alafenamide (TAF), a new tenofovir prodrug, has been developed to circumvent the less favorable safety profile of tenofovir disoproxil fumarate (TDF). We investigated reductions in hepatitis B surface antigen (HBsAg) levels in patients with HBV infection who received continuous entecavir (ETV) monotherapy or sequential therapy with ETV and TAF. METHODS: This retrospective cohort study included 286 patients who were divided into two groups: continuous ETV monotherapy (ETV group, n = 168) and sequential therapy with ETV and TAF (ETV-TAF group, n = 108). Factors associated with a 90% reduction in HBsAg levels were analyzed by a Cox proportional hazards model using a time-dependent covariate in both groups. RESULTS: In the multivariate Cox proportional hazards model, the ETV-TAF group [adjusted hazard ratio (aHR) 2.750; 95% confidence interval (CI), 1.265-3.405; P = 0.0038] and BMI ≤ 25.0 kg/m2 (aHR 0.520, 95% CI, 0.308-0.875; P = 0.0139) demonstrated a 90% reduction in HBsAg levels. HBsAg levels of patients in the TAF phase in the ETV-TAF group showed greater yearly percent reductions than those in the ETV group and those in the ETV phase in the ETV-TAF group (P = 0.0361 and P = 0.0022, respectively, Steel-Dwass test). CONCLUSION: HBsAg levels decreased more rapidly after patients switched from ETV to TAF. Switching to TAF may be an effective treatment option to reduce HBsAg levels.

    DOI: 10.1097/MEG.0000000000002292

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  10. Cationic surface charge effect on proliferation and protein production of human dental pulp stem cells cultured on diethylaminoethyl-modified cellulose porous beads

    Oki Yuichiro, Harano Kodai, Hara Yuichi, Sasajima Yoshiyuki, Sasaki Ryo, Ito Takanori, Fujishiro Mitsuhiro, Ito Taichi

    BIOCHEMICAL ENGINEERING JOURNAL   176 巻   2021年12月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Biochemical Engineering Journal  

    Human adult dental pulp stem cells (DPSCs) are a type of mesenchymal stem cells (MSCs). Recently, DPSCs have been proposed as a new MSC source for treating immune-mediated, inflammatory, and degenerative diseases via cell-based therapy. Hence, large-scale industrial production of the required cell number will be necessary. In this study, to investigate the cationic surface charge effect on DPSC proliferation, we fabricated two types of 2-diethylaminoethyl -modified cellulose porous beads (CPB-DEAE) with different ion exchange capacities. The cationic surface charge effect increased with increase in DPSC proliferation rate for the ion exchange capacity of 0.55–1.82 meq/g. However, the DPSC proliferation rate decreased at 2.50 meq/g. Thus, the optimal ion exchange capacity was determined to be 1.82 meq/g for DPSC proliferation. Additionally, the total amount of protein produced from the DPSCs on the CPB-DEAE microcarriers was higher than that produced under the conventional monolayer culture conditions. Furthermore, the hepatocyte growth factor, which is one of the anti-inflammatory growth factors, was produced from the DPSCs on the CPB-DEAE microcarriers. Finally, the DPSCs were confirmed to maintain their proliferative and multidifferentiation ability after culture on the CPB-DEAE microcarriers. CPB-DEAE microcarriers have the potential to be used for large-scale MSC expansion and protein production.

    DOI: 10.1016/j.bej.2021.108217

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  11. Increased risk of thyroid dysfunction by PD-1 and CTLA-4 blockade in patients without thyroid autoantibodies at baseline.

    Iwama S, Kobayashi T, Yasuda Y, Okuji T, Ito M, Ando M, Zhou X, Yamagami A, Onoue T, Kawaguchi Y, Miyata T, Sugiyama M, Takagi H, Hagiwara D, Suga H, Banno R, Hase T, Morise M, Wakahara K, Yokota K, Kato M, Nishio N, Tanaka C, Miyata K, Ogura A, Ito T, Sawada T, Shimokata T, Niimi K, Ohka F, Ishigami M, Gotoh M, Hashimoto N, Saito R, Kiyoi H, Kajiyama H, Ando Y, Hibi H, Sone M, Akiyama M, Kodera Y, Arima H

    The Journal of clinical endocrinology and metabolism     2021年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1210/clinem/dgab829

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

    Yamamoto K, Honda T, Yokoyama S, Ma L, Kato A, Ito T, Ishizu Y, Kuzuya T, Nakamura M, Kawashima H, Ishigami M, Tsuji NM, Fujishiro M

    Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver   53 巻 ( 11 ) 頁: 1443 - 1450   2021年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   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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  13. Safety and Efficacy of Glass Membrane Pumping Emulsification Device in Transarterial Chemoembolization for Hepatocellular Carcinoma: First Clinical Outcomes.

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

    Anticancer research   41 巻 ( 11 ) 頁: 5817 - 5820   2021年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   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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  14. Basigin deficiency prevents anaplerosis and ameliorates insulin resistance and hepatosteatosis.

    Ryuge A, Kosugi T, Maeda K, Banno R, Gou Y, Zaitsu K, Ito T, Sato Y, Hirayama A, Tsubota S, Honda T, Nakajima K, Ozaki T, Kondoh K, Takahashi K, Kato N, Ishimoto T, Soga T, Nakagawa T, Koike T, Arima H, Yuzawa Y, Minokoshi Y, Maruyama S, Kadomatsu K

    JCI insight   6 巻 ( 20 )   2021年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JCI Insight  

    Monocarboxylates, such as lactate and pyruvate, are precursors for biosynthetic pathways, including those for glucose, lipids, and amino acids via the tricarboxylic acid (TCA) cycle and adjacent metabolic networks. The transportation of monocarboxylates across the cellular membrane is performed primarily by monocarboxylate transporters (MCTs), the membrane localization and stabilization of which are facilitated by the transmembrane protein basigin (BSG). Here, we demonstrate that the MCT/BSG axis sits at a crucial intersection of cellular metabolism. Abolishment of MCT1 in the plasma membrane was achieved by Bsg depletion, which led to gluconeogenesis impairment via preventing the influx of lactate and pyruvate into the cell, consequently suppressing the TCA cycle. This net anaplerosis suppression was compensated in part by the increased utilization of glycogenic amino acids (e.g., alanine and glutamine) into the TCA cycle and by activated ketogenesis through fatty acid β-oxidation. Complementary to these observations, hyperglycemia and hepatic steatosis induced by a high-fat diet were ameliorated in Bsg-deficient mice. Furthermore, Bsg deficiency significantly improved insulin resistance induced by a high-fat diet. Taken together, the plasma membrane–selective modulation of lactate and pyruvate transport through BSG inhibition could potentiate metabolic flexibility to treat metabolic diseases.

    DOI: 10.1172/jci.insight.142464

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

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

    Pediatrics international : official journal of the Japan Pediatric Society   63 巻 ( 10 ) 頁: 1223 - 1229   2021年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   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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  16. USEFULNESS OF CORE I97L IN PREDICTING THE EFFICACY OF NUCLEOS(T)IDE ANALOGUE THERAPY IN PATIENTS WITH HEPATITIS B

    TakashiHonda, MasatoshiIshigami, ShinyaYokoyama, Yamamoto Kenta, Ito Takanori, Imai Norihiro, Ishizu Yoji, Ishikawa Tetsuya, Fujishiro Mitsuhiro

    HEPATOLOGY   74 巻   頁: 468A - 469A   2021年10月

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  17. CONDITIONED MEDIUM FROM STEM CELLS DERIVED FROM HUMAN EXFOLIATED DECIDUOUS TEETH AMELIORATES NASH VIA THE GUT-LIVER AXIS

    Muto Hisanori, Ito Takanori, Ishigami Masatoshi

    HEPATOLOGY   74 巻   頁: 1134A - 1134A   2021年10月

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  18. Clinical course of liver injury induced by immune checkpoint inhibitors in patients with advanced malignancies.

    Ito T, Ishigami M, Yamamoto T, Mizuno K, Yamamoto K, Imai N, Ishizu Y, Honda T, Kawashima H, Yasuda S, Toyoda H, Yokota K, Hase T, Nishio N, Maeda O, Kato M, Hashimoto N, Hibi H, Kodera Y, Sone M, Ando Y, Akiyama M, Shimoyama Y, Fujishiro M

    Hepatology international   15 巻 ( 5 ) 頁: 1278 - 1287   2021年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Hepatology International  

    Background: The clinical course of liver injury induced by immune checkpoint inhibitors (ICIs) varies among individuals, and there were few reports on the therapeutic effects of corticosteroids based on the patterns of liver injury. Methods: We evaluated the characteristics and clinical course of immune-related liver injury in 1214 patients treated with ICIs for advanced malignancies except for hepatocellular carcinoma between August 2014 and May 2021. Results: During the follow-up period (median, 252 days), 58 patients (4.8%) had an immune-related liver injury (≥ Grade 3). The liver-injury patterns were hepatocellular (n = 26, 44.8%), mixed (n = 11, 19.0%), or cholestatic (n = 21, 36.2%), and the median time to onset of liver injury was 39, 81, and 53 days, respectively; the hepatocellular pattern occurred earlier than the other types (p = 0.047). Corticosteroids were administered to 30 (51.7%) patients; while liver injury was improved in almost all patients with the hepatocellular pattern (n = 13/14, 92.9%), that failed to show improvement in over half of the patients with the non-hepatocellular patterns, and three patients with mixed patterns needed secondary immunosuppression with mycophenolate mofetil. Liver biopsies performed in 13 patients mainly showed lobular injury, endothelialitis, and spotty necrosis with infiltration of T cells positive for CD3 and CD8, but not CD4 or CD20. Conclusion: The incidence pattern and therapeutic response to corticosteroids in immune-related liver injury differ according to the injury type. Although corticosteroids were effective for the hepatocellular pattern, an additional strategy for refractory non-hepatocellular patterns is needed.

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

    Muto H, Ito T, Tanaka T, Yokoyama S, Yamamoto K, Imai N, Ishizu Y, Maeda K, Honda T, Ishikawa T, Kato A, Ohshiro T, Kano F, Yamamoto A, Sakai K, Hibi H, Ishigami M, Fujishiro M

    Scientific reports   11 巻 ( 1 ) 頁: 18778   2021年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   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.

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  20. Revisiting Prognosis After Liver Transplant in Patients Positive for Hepatitis C Virus: Focus on Hepatitis C Recurrence-Unrelated Complications.

    Ishigami M, Honda T, Ishizu Y, Imai N, Ito T, Yamamoto K, Kamei H, Ogura Y, Fujishiro M

    Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation   19 巻 ( 9 ) 頁: 935 - 942   2021年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Experimental and Clinical Transplantation  

    Objectives: In this study, we revisited the reasons for poorer prognosis after liver transplant in patients with hepatitis C virus, whose main causes of death were generally known to be recurrent disease. Materials and Methods: Between April 2003 and March 2017, among 132 patients who underwent liver transplant because of liver cirrhosis at our institution, 40 patients (30.3%) were positive for hepatis C virus. We retrospectively compared the overall survival after liver transplant in patients with and without hepatitis C virus infection. Furthermore, we investigated the causes of death in transplant recipients with hepatitis C virus infections. Results: In patients with hepatitis C virus infection, overall survival was 82.2%, 75.2%, and 50.8% at 1, 5, and 10 years, respectively, after liver transplant; these results were lower than those in patients without infection (94.5%, 87.0%, and 87.0% at 1, 5, and 10 years, respectively; P = .001). Among 40 patients with positive infection, 14 patients died after liver transplant. A main reason for death was hepatocellular carcinoma recurrence (3 patients). Surprisingly, only 1 patient died from hepatitis C virus-related complication (fibrosing cholestatic hepatitis); the remaining 10 patients died from reasons other than hepatitis C virus disease progression. Conclusions: Our results suggest that clinicians should not only be aware of hepatitis C virus recurrence but should also be aware of other unrelated complications in transplant recipients who are positive for this virus.

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  21. Long-term outcomes of viral eradication in patients with hepatitis C virus infection and mild hepatic fibrosis.

    Kumada T, Toyoda H, Yasuda S, Tada T, Ito T, Tanaka J

    Journal of viral hepatitis   28 巻 ( 9 ) 頁: 1293 - 1303   2021年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Journal of Viral Hepatitis  

    The impact of antiviral therapy on clinical outcomes in patients with hepatitis C virus (HCV) infection and mild liver fibrosis (FIB-4 score <1.45) is not well understood. We aimed to clarify the impact of viral eradication on hepatocarcinogenesis and mortality in patients with mild fibrosis.The subjects were 657 patients who achieved sustained virologic response (SVR) (Clearance group) and 586 patients who did not receive antiviral therapy or did not achieve SVR (No clearance group). We applied inverse probability weighting because the groups had different baseline characteristics. Multivariate proportional hazards models were used to analyse factors associated with hepatocarcinogenesis and mortality using a time-dependent covariate. In addition, we compared the mortality rate of the Clearance group stratified by age to the mortality rate of the general population.Clearance of HCV RNA was significantly associated with hepatocarcinogenesis and all-cause, liver-related and non–liver-related mortality (adjusted hazard ratios [95% confidence interval], 0.2653 [0.1147–0.6136, p = 0.0019], 0.3416 [0.2157–0.5409, p < 0.0001], 0.2474 [0.0802–0.8917, p = 0.0381] and 0.4118 [0.2449–0.6925, p = 0.0008], respectively). The Clearance group had significantly higher mortality than the general population matched by age, sex and follow-up duration (p < 0.0001). However, there were no significant differences between patients who achieved SVR before age 50 and the general population matched by age, sex and follow-up duration (p = 0.1570). HCV eradication in patients with mild fibrosis reduces liver-related and non–liver-related mortality. If HCV is eradicated before age 50, prognosis is likely be similar to that of the age-matched and sex-matched general population. (249 words).

    DOI: 10.1111/jvh.13562

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  22. Transient deterioration of albumin-bilirubin scores in early post-dose period of molecular targeted therapies in advanced hepatocellular carcinoma with 50% or higher liver occupation: A STROBE-compliant retrospective observational study.

    Muto H, Kuzuya T, Ito T, Ishizu Y, Honda T, Ishikawa T, Ishigami M, Fujishiro M

    Medicine   100 巻 ( 31 ) 頁: e26820   2021年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Medicine  

    ABSTRACT: Real-world clinical cases of molecularly targeted agent (MTA) administration to patients with advanced hepatocellular carcinoma (HCC) with ≥50% liver occupation have been reported, but treatment outcomes have rarely been described. We have encountered several cases in which albumin-bilirubin (ALBI) scores deteriorated markedly and C-reactive protein (CRP) levels elevated in the early post-dose period. The present study therefore investigated early clinical changes in ALBI score and CRP levels after initiating MTA in advanced HCC patients with ≥50% liver occupation, focusing on antitumor response at 6 weeks.This retrospective study included 46 HCC patients with liver occupation ≥50% and 191 patients with <50%, Child-Pugh score ≤7, and Eastern Cooperative Oncology Group Performance Status scores of 0 or 1, who were treated with sorafenib or lenvatinib as first-line systemic therapy at our hospital between June 2011 and January 2020. We analyzed their medical records up to March 2020 and investigated the outcomes and changes in CRP and ALBI scores classified according to antitumor response at 6 weeks.Overall survival was significantly longer in patients with partial response (PR) + stable disease (SD) (13.7 months) than in patients with progressive disease (PD) (1.7 months, P < .001) in the ≥50% group. Patients with antitumor response of PR + SD at 6 weeks in the ≥50% group showed more marked deterioration of ALBI score at 2 weeks than those in the <50% group. These significant differences between groups had again disappeared at 4 and 6 weeks. Focusing on patients with PD at 6 weeks, ALBI score deteriorated over time in both groups. Regarding CRP, on 6-week PR + SD patients, a significant increase in CRP levels at 1 and 2 weeks was evident in the >50% group compared to the <50% group. These significant differences between groups had again disappeared at 4 and 6 weeks. In PD patients, no difference between groups in CRP elevation occurred at 1 and 2 weeks.In MTA treatment for patients with ≥50% liver occupation, to obtain an antitumor response of PR + SD, adequate management might be important considering transient deteriorated ALBI scores and elevated CRP levels.

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  23. The impact of hepatitis C virus eradication on hepatocarcinogenesis in haemophiliacs

    Inukai Yosuke, Imai Norihiro, Yamamoto Kenta, Ito Takanori, Ishizu Yoji, Honda Takashi, Ishigami Masatoshi

    JOURNAL OF HEPATOLOGY   75 巻   頁: S787 - S788   2021年7月

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  24. Prediction of Hepatocellular Carcinoma by Liver Stiffness Measurements Using Magnetic Resonance Elastography After Eradicating Hepatitis C Virus.

    Kumada T, Toyoda H, Yasuda S, Sone Y, Ogawa S, Takeshima K, Tada T, Ito T, Sumida Y, Tanaka J

    Clinical and translational gastroenterology   12 巻 ( 4 ) 頁: e00337   2021年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Clinical and translational gastroenterology  

    INTRODUCTION: Liver fibrosis stage is one of the most important factors in stratifying the risk of developing hepatocellular carcinoma (HCC). We evaluated the usefulness of liver stiffness measured by magnetic resonance elastography (MRE) to stratify the risk of developing HCC in patients who underwent MRE before receiving direct-acting antivirals (DAAs) and subsequently achieved sustained virological response (SVR). METHODS: A total of 537 consecutive patients with persistent hepatitis C virus who underwent initial MRE before DAA therapy and achieved SVR were enrolled. Factors associated with HCC development were analyzed by univariate and multivariate Cox proportional hazards models. RESULTS: Albumin-bilirubin score ≥ -2.60 (adjusted hazard ratio [aHR] 6.303), fibrosis-4 (FIB-4) score >3.25 (aHR 7.676), and MRE value ≥4.5 kPa (aHR 13.190) were associated with HCC development according to a univariate Cox proportional hazards model. A multivariate Cox proportional hazards model showed that an MRE value ≥4.5 kPa (aHR 7.301) was the only factor independently associated with HCC development. Even in patients with an FIB-4 score >3.25, the cumulative incidence rate of HCC development in those with an MRE value <4.5 kPa was significantly lower than that in patients with an MRE value ≥4.5 kPa. DISCUSSION: Liver stiffness measured by MRE before DAA therapy was an excellent marker for predicting subsequent HCC development in patients with hepatitis C virus infection who achieved SVR. The same results were observed in patients with high FIB-4 scores.

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  25. Filtrated Adipose Tissue-Derived Mesenchymal Stem Cell Lysate Ameliorates Experimental Acute Colitis in Mice.

    Nishikawa T, Maeda K, Nakamura M, Yamamura T, Sawada T, Mizutani Y, Ito T, Ishikawa T, Furukawa K, Ohno E, Miyahara R, Kawashima H, Honda T, Ishigami M, Yamamoto T, Matsumoto S, Hotta Y, Fujishiro M

    Digestive diseases and sciences   66 巻 ( 4 ) 頁: 1034 - 1044   2021年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Digestive Diseases and Sciences  

    Background: Inflammatory bowel disease (IBD) is a chronic, persistent, and intractable enteritis; however, an effective treatment strategy is yet to be established. Mesenchymal stem cells (MSCs) and their paracrine factors exhibit anti-inflammatory actions and have been proposed as a new therapeutic candidate for IBD treatment, although the efficacy of MSC lysate on enteritis is unclear. Aims: Here, we examined the efficacy and appropriate regimen of filtrated murine adipose-derived mesenchymal stem cell lysate (FADSTL) in an acute colitis mouse model as a novel cell-free MSC therapy. Methods: To confirm the clinical effects of FADSTL, survival rate, body weight, and disease activity index (DAI) were investigated in the DSS-induced colitis mouse model. Further, differences in efficacy with dosing frequency were assessed to optimize the proper regimen. Colon length, histological findings, gene expression of inflammatory mediators and tight junction proteins in colon tissues, and anti-apoptotic effects were also compared in 3-day continuous FADSTL administration and PBS groups. Results: Three-day continuous FADSTL administration significantly improved weight loss and DAI score compared to those in the PBS-treated group, whereas the effect was not observed with single administration. Additionally, colon shortening and histological inflammation were suppressed in the FADSTL-treated group. Further, this treatment decreased gene expression of inflammatory mediators, maintained expression of tight junction proteins in the colon, and showed anti-apoptotic effects. Conclusions: FADSTL effects were dependent on its administration frequency, suggesting the requirement of continuous FADSTL administration. FADSTL improved colitis by maintaining the intestinal barrier function through its anti-inflammatory and anti-apoptotic actions.

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  26. Impact of visceral fat accumulation on the prognosis of patients with cirrhosis.

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

    Clinical nutrition ESPEN   42 巻   頁: 354 - 360   2021年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Clinical Nutrition ESPEN  

    Background & aims: The impact of obesity, evaluated using body mass index (BMI), on mortality in patients with cirrhosis is controversial. The prognostic impact of visceral fat accumulation, which is recommended as an indicator of obesity-related mortality, is still unknown. This study aimed to clarify the impact of visceral fat accumulation on mortality in patients with cirrhosis. Methods: A total of 335 cirrhotic patients without hepatocellular carcinoma were retrospectively evaluated. The impact of obesity, defined as a visceral fat area ≥100 cm2 at the umbilical level or BMI ≥25 kg/m2 on mortality, was evaluated using competing risk analysis. Results: Of 355 patients, visceral fat accumulation was seen in 147 patients. During the observation period (1340 ± 980 days), 84 patients died, and 17 received liver transplantation. Visceral fat accumulation was not found to be associated with mortality (hazard ratio [HR] 1.423, P = 0.180) in any of the patients. After stratification of the patients, visceral fat accumulation was observed to be associated with a poor prognosis in patients with skeletal muscle depletion (HR 3.804, P = 0.003), but not in those without (HR 1.147, P = 0.660). On the other hand, obesity defined by BMI ≥25 kg/m2 was not found to be associated with mortality in patients with (HR 0.341, P = 0.390) or without skeletal muscle depletion (HR 1.227, P = 0.500). Conclusions: Visceral fat accumulation is a useful index for evaluating obesity and aggravates mortality in cirrhotic patients with skeletal muscle depletion, but not in those without.

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  27. The epidemiology of NAFLD and lean NAFLD in Japan: a meta-analysis with individual and forecasting analysis, 1995-2040.

    Ito T, Ishigami M, Zou B, Tanaka T, Takahashi H, Kurosaki M, Maeda M, Thin KN, Tanaka K, Takahashi Y, Itoh Y, Oniki K, Seko Y, Saruwatari J, Kawanaka M, Atsukawa M, Hyogo H, Ono M, Ogawa E, Barnett SD, Stave CD, Cheung RC, Fujishiro M, Eguchi Y, Toyoda H, Nguyen MH

    Hepatology international   15 巻 ( 2 ) 頁: 366 - 379   2021年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Hepatology International  

    Background: NAFLD is increasing in Asia including Japan, despite its lower obesity rate than the West. However, NAFLD can occur in lean people, but data are limited. We aimed to investigate the epidemiology of NAFLD in Japan with a focus on lean NAFLD. Methods: We searched PubMed, Cochrane Library, EMBASE, Web of Science, and the Japan Medical Abstracts Society (inception to 5/15/2019) and included 73 eligible full-text original research studies (n = 258,531). We used random-effects model for pooled estimates, Bayesian modeling for trend and forecasting, contacted authors for individual patient data and analyzed 14,887 (7752 NAFLD; 7135 non-NAFLD—8 studies) patients. Results: The overall NAFLD prevalence was 25.5%, higher in males (p < 0.001), varied by regions (p < 0.001), and increased over time (p = 0.015), but not by per-person income or gross prefectural productivity, which increased by 0.64% per year (1983–2012) and is forecasted to reach 39.3% in 2030 and 44.8% in 2040. The incidence of NAFLD, HCC, and overall mortality were 23.5, 7.6 and 5.9 per 1000 person-years, respectively. Individual patient-level data showed a lean NAFLD prevalence of 20.7% among the NAFLD population, with lean NAFLD persons being older and with a higher all-cause mortality rate (8.3 vs. 5.6 per 1000 person-years for non-lean NAFLD, p = 0.02). Older age, male sex, diabetes, and FIB-4 were independent predictors of mortality, but not lean NAFLD. Conclusion: NAFLD prevalence has increased in Japan and may affect half of the population by 2040. Lean NAFLD individuals makeup 20% of the NAFLD population, were older, and had higher mortality.

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  28. The relationship between oral-origin bacteria in the fecal microbiome and albumin-bilirubin grade in patients with hepatitis C.

    Yamamoto K, Honda T, Ito T, Ishizu Y, Kuzuya T, Nakamura M, Miyahara R, Kawashima H, Ishigami M, Fujishiro M

    Journal of gastroenterology and hepatology   36 巻 ( 3 ) 頁: 790 - 799   2021年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Journal of Gastroenterology and Hepatology (Australia)  

    Background: Bacteria of oral origin (BO) in the gut are associated with prognosis in patients with cirrhosis. The Greengenes database (gg_13_8) is widely used in microbiome analysis, but the expanded Human Oral Microbiome Database (eHOMD), a specialized database for BO, can add more detailed information. We used each database to evaluate the relationship between the albumin–bilirubin grade (ALBI) and the microbiome in patients with hepatitis C. Methods: Eighty patients were classified into the low ALBI group (LA; n = 34) or high ALBI group (HA; n = 46). Isolated DNA from stool was amplified to target the V3–4 regions of 16S rRNA. The microbiomes of the two groups were compared using gg_13_8 or eHOMD. We evaluated the associations between microbiomes and prognoses using Cox proportional hazards models. Results: At the genus level, the two groups differed significantly regarding 6 (gg_13_8) and 7 (eHOMD) types of bacteria. All types except Akkermansia are classified as BO. Both databases showed an increase in Streptococcus and Veillonella. eHOMD showed a decrease in Fusobacterium and an increase in Fretibacterium; both produce various types of short-chain fatty acids. At the species level, the two groups demonstrated significant differences in 2 (gg_13_8) and 6 (eHOMD) bacterial types. Selenomonas noxia and Streptococcus salivarius were related to poor prognosis in univariate analysis. Conclusion: The HA group demonstrated increased BO, most of which produce lactic acid or acetic acid. The correlation between the microbiome and metabolism might be related to prognosis. eHOMD was a useful database for analyzing BO.

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  29. Long-term prognosis with or without nucleot(s)ide analogue therapy in hepatitis B virus-related decompensated cirrhosis.

    Kumada T, Toyoda H, Yasuda S, Miyake N, Ito T, Tanaka J

    Journal of viral hepatitis   28 巻 ( 3 ) 頁: 508 - 516   2021年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Journal of Viral Hepatitis  

    The development of nuleos(t)ide analogues (NAs) has dramatically changed the natural history of chronic hepatitis B virus (HBV) infection. In this study, we compared patients with HBV-related decompensated cirrhosis with and without NA therapy in terms of hepatocarcinogenesis and all-cause, liver-related, and non–liver-related mortality. This study enrolled 160 patients with decompensated cirrhosis, 78 of whom were treated with NA therapy (NA group) and 82 of whom were not (non-NA group). Propensity score matching and inverse probability weighting were performed to adjust the baseline characteristics in the NA and non-NA groups. Liver-related and non–liver-related mortality were analysed using the competing risks IPW cumulative incidence functions estimator. The Cox proportional hazards model and the Fine and Gray proportional hazards model were used to analyse factors associated with hepatocarcinogenesis and all-cause, liver-related, and non–liver-related mortality. HBV DNA ≥20,000 IU/ml (adjusted hazard ratio [aHR], 8.440) and dyslipidemia (aHR, 0.178) were independently associated with hepatocarcinogenesis. HBV DNA ≥20,000 IU/ml (aHR, 4.360) and non-NA group (aHR, 4.802) were independently associated with all-cause mortality. Diabetes mellitus (aHR, 4.925), FIB-4 score >3.6 (aHR, 4.151), non-NA group (aHR, 9.180), presence of dyslipidemia (aHR, 0.182) and male gender (aHR, 3.045) were independently associated with liver-related mortality. HBV DNA ≥20,000 IU/ml (aHR, 3.216) and high age (aHR, 2.692) were independently associated with non–liver-related mortality. Although the cumulative incidence rate of hepatocarcinogenesis and non–liver-related mortality was not reduced by NA therapy, viral suppression reduced liver-related mortality in patients with DC.

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  30. Simplification of balloon-occluded retrograde transcatheter obliteration procedure using a coaxial double balloon catheter compared with a single-balloon catheter.

    Ishizu Y, Ishigami M, Honda T, Kuzuya T, Ito T, Komada T, Fujishiro M

    Japanese journal of radiology   39 巻 ( 3 ) 頁: 296 - 302   2021年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Japanese Journal of Radiology  

    Purpose: This study aimed to evaluate the usefulness of a coaxial double balloon catheter for simplification of the balloon-occluded retrograde transcatheter obliteration (BRTO) procedure compared with a single-balloon catheter. Materials and methods: Thirty-three patients who underwent BRTO with a single-balloon catheter (Single-balloon group, n = 15) or a coaxial double balloon catheter (Coaxial group, n = 18) were included, retrospectively. The frequency of additional procedures for stagnation of sclerosant including ethanol injection, coil embolization, and additional balloon occlusion for collateral draining veins; the dose of ethanolamine oleate (EO); and the complication rate and the success rate of sclerosant stagnation were evaluated. Results: Additional procedures were needed in four patients in the Coaxial group, which was significantly lower than that in the Single-balloon group (nine patients, P = 0.038). The dose of EO in the Coaxial group (11.2 ± 6.6 g) was lower, but not significantly different than that in the Single-balloon group (14.4 g ± 6.1 g, P = 0.184). The complication rate and the success rate of sclerosant stagnation were not different between the two groups. Conclusion: The use of a coaxial double balloon catheter can simplify the BRTO procedure compared with a single-balloon catheter.

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  31. Safety and efficacy of percutaneous radiofrequency ablation for hepatocellular carcinoma patients with haemophilia.

    Yamamoto T, Imai N, Yamamoto K, Ito T, Ishizu Y, Honda T, Okamoto S, Kanematsu T, Suzuki N, Matsushita T, Ishigami M, Fujishiro M

    Haemophilia : the official journal of the World Federation of Hemophilia   27 巻 ( 1 ) 頁: 100 - 107   2021年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Haemophilia  

    Haemophilia is an X-linked inherited bleeding disorder caused by coagulation factor deficiency. Hepatocellular carcinoma (HCC) is a major complication associated with the disease. No study thus far has investigated the safety and efficacy of percutaneous radiofrequency ablation (RFA) for HCC in patients with haemophilia. Aim: This study aimed to evaluate the safety and efficacy of RFA for HCC in haemophilia patients. Methods: From July 2008 to June 2019, 217 patients with HCC underwent 300 RFA sessions. Of these, 18 sessions were performed in ten haemophilia patients (H group) and 282 in 207 non-haemophilia patients (NH group). The patients' characteristics, incidence of haemorrhagic complications and rates of local tumour recurrence were compared between the groups. Results: A majority of the haemophilia patients received clotting factor concentrate replacement therapy before and after RFA treatment, with the aim of reaching a plasma clotting factor level of higher than 60%–80%. Twelve haemorrhagic complications were observed in the NH group (4.2%; 12/282). Major bleeding requiring control procedures was observed in two patients and minor bleeding with careful observation was noted in ten patients. No bleeding complications were observed in the H group (0/18). There were no significant differences in the 5-year local tumour recurrence rates after RFA treatment between the groups (35.0% in the H group and 32.1% in the NH group). Conclusion: RFA could be an effective and a safe method for HCC treatment in patients with haemophilia.

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  32. Amino Acid Polymorphism in Hepatitis B Virus Associated With Functional Cure.

    Honda T, Yamada N, Murayama A, Shiina M, Aly HH, Kato A, Ito T, Ishizu Y, Kuzuya T, Ishigami M, Murakami Y, Tanaka T, Moriishi K, Nishitsuji H, Shimotohno K, Ishikawa T, Fujishiro M, Muramatsu M, Wakita T, Kato T

    Cellular and molecular gastroenterology and hepatology   12 巻 ( 5 ) 頁: 1583 - 1598   2021年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Cellular and Molecular Gastroenterology and Hepatology  

    Background & Aims: To provide an adequate treatment strategy for chronic hepatitis B, it is essential to know which patients are expected to have a good prognosis and which patients do not require therapeutic intervention. Previously, we identified the substitution of isoleucine to leucine at amino acid 97 (I97L) in the hepatitis B core region as a key predictor among patients with stable hepatitis. In this study, we attempted to identify the point at which I97L affects the hepatitis B virus (HBV) life cycle and to elucidate the underlying mechanisms governing the stabilization of hepatitis. Methods: To confirm the clinical features of I97L, we used a cohort of hepatitis B e antigen–negative patients with chronic hepatitis B infected with HBV-I97 wild-type (wt) or HBV-I97L. The effects of I97L on viral characteristics were evaluated by in vitro HBV production and infection systems with the HBV reporter virus and cell culture-generated HBV. Results: The ratios of reduction in hepatitis B surface antigen and HBV DNA were higher in patients with HBV-I97L than in those with HBV-I97wt. HBV-I97L exhibited lower infectivity than HBV-I97wt in both infection systems with reporter HBV and cell culture-generated HBV. HBV-I97L virions exhibiting low infectivity primarily contained a single-stranded HBV genome. The lower efficiency of cccDNA synthesis was demonstrated after infection of HBV-I97L or transfection of the molecular clone of HBV-I97L. Conclusions: The I97L substitution reduces the level of cccDNA through the generation of immature virions with single-stranded genomes. This I97L-associated low efficiency of cccDNA synthesis may be involved in the stabilization of hepatitis.

    DOI: 10.1016/j.jcmgh.2021.07.013

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  33. 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   掲載種別:研究論文(学術雑誌)   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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  34. SAFETY AND EFFICACY OF PERCUTANEOUS RADIOFREQUENCY ABLATION FOR HEPATOCELLULAR CARCINOMA PATIENTS WITH HEMOPHILIA

    Yamamoto Takafumi, Ishigami Masatoshi, Yamamoto Kenta, Ito Takanori, Imai Norihiro, Lshizu Yoji, Honda Takashi, Fujishiro Mitsuhiro

    HEPATOLOGY   72 巻   頁: 705A - 706A   2020年11月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  35. GUT MICROBIOTA ASSOCIATED WITH THE DIFFERENCE BETWEEN PATIENTS WITH AND WITHOUT HEPATOCELLULAR CARCINOMA IN CHRONIC LIVER DISEASE

    Honda Takashi, Ishigami Masatoshi, Yamamoto Kenta, Ito Takanori, Imai Norihiro, Ishizu Yoji, Fujishiro Mitsuhiro

    HEPATOLOGY   72 巻   頁: 370A - 370A   2020年11月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  36. IMPROVEMENT OF LIVER FUNCTIONAL RESERVE AFTER SVR IN HCV-PATIENTS WITH COMPENSATED, SEVERE FIBROSIS BY IFN-FREE, DAA COMBINATION TREATMENT-IMPACT OF PRETREATMENT SERUM AFP LEVELS

    Ishigami Masatoshi, Honda Takashi, Ishizu Yoji, Imai Norihiro, Ito Takanori, Yamamoto Kenta, Fujishiro Mitsuhiro

    HEPATOLOGY   72 巻   頁: 564A - 565A   2020年11月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  37. AMINO ACID POLYMORPHISM IN HEPATITIS B VIRUS ASSOCIATED WITH NATURAL CLEARANCE OF HBV DNA AND HBsAg

    Honda Takashi, Yamada None, Murayama Asako, Kato Asuka, Ito Takanori, Ishizu Yoji, Kuzuya Teiji, Ishigami Masatoshi, Murakami Yoshiki, Ishikawa Tetsuya, Fujishiro Mitsuhiro, Kato Takanobu

    HEPATOLOGY   72 巻   頁: 508A - 509A   2020年11月

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    掲載種別:研究論文(学術雑誌)  

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  38. The albumin-bilirubin score as a predictor of outcomes in Japanese patients with PBC: an analysis using time-dependent ROC.

    Ito T, Ishigami M, Morooka H, Yamamoto K, Imai N, Ishizu Y, Honda T, Nishimura D, Tada T, Yasuda S, Toyoda H, Kumada T, Fujishiro M

    Scientific reports   10 巻 ( 1 ) 頁: 17812   2020年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Scientific Reports  

    The albumin–bilirubin (ALBI) score is calculated using only serum albumin and bilirubin levels, and was developed as a simple method to assess hepatic function. In this study, a total of 409 patients with primary biliary cholangitis (PBC) were enrolled between March 1990 and October 2018. The predictive performances of the ALBI score and other well-established prognostic scores were compared using time-dependent receiver operating characteristic (ROC) analysis. During the follow-up period, 60 patients died, 45 due to liver-related diseases and 15 due to non-liver-related diseases, and 16 patients underwent liver transplantation. Time-dependent ROC analysis showed that the ALBI score has higher the areas under the ROC curves (AUROCs) than the Child–Pugh (C–P) score at each time point; AUROCs at 3, 5, and 10 years after the start of follow-up were 0.94, 0.91, and 0.90 for the ALBI score, and 0.89, 0.88, and 0.82 for the C–P score, respectively. The ALBI score showed the highest AUROCs within 2 years after the start of observation; beyond 2 years, however, the Mayo score had better prognostic ability for mortality and liver transplantation. The ALBI score/grade, derived from objective blood tests, and the Mayo score were superior prognostic tools in PBC patients.

    DOI: 10.1038/s41598-020-74732-3

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  39. Revisiting the indications for liver transplantation in cirrhotic patients considering the long-term outcomes of cirrhotic patients.

    Ishigami M, Honda T, Kuzuya T, Ishizu Y, Ito T, Kamei H, Ogura Y, Fujishiro M

    Journal of hepato-biliary-pancreatic sciences   27 巻 ( 9 ) 頁: 655 - 662   2020年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Journal of Hepato-Biliary-Pancreatic Sciences  

    Background: In this study, we investigated long-term survival of cirrhotic patients without hepatocellular carcinoma (HCC) and the proper timing of liver transplantation in the era with recent progress of management. Methods: We first classified 217 non-transplant cirrhotic patients without HCC according to the long-term survival based on Child-Turcotte-Pugh (CTP) scores and the MELD scores. We then compared them with the survival after liver transplantation in 114 patients with liver cirrhosis. Results: We classified into four groups (class A as CTP score of 5,6, B as 7,8, C as 9-12, D as 13-15) according to the long-term survival of the patients, the survivals of patients with class C and D were significantly worse compared with transplant patients (P < 0.001 in each group). And we also classified into four groups based on the MELD scores (class A as MELD score of −8, B as 9-12, C as 13-19, D as 19-), the survivals of patients with class C and D were significantly worse compared with those of transplant patients (P < 0.001 in each group). Conclusions: Considering the long-term survival of patients with liver cirrhosis, CTP score of 9 and/or MELD score of 13 could be a proper timing for liver transplantation.

    DOI: 10.1002/jhbp.777

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  40. Editorial: impact of the introduction of direct-acting anti-viral drugs on hepatocarcinogenesis-a prospective serial follow-up MRI study.

    Ito T

    Alimentary pharmacology & therapeutics   52 巻 ( 4 ) 頁: 735 - 736   2020年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Alimentary Pharmacology and Therapeutics  

    DOI: 10.1111/apt.15911

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  41. Limitation of non-transplant treatment and proper timing for liver transplantation in patients with hepatocellular carcinoma considering long-term survival.

    Nomura A, Ishigami M, Honda T, Kuzuya T, Ishizu Y, Ito T, Kamei H, Onishi Y, Ogura Y, Fujishiro M

    Medicine   99 巻 ( 28 ) 頁: e21161   2020年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Medicine (United States)  

    DOI: 10.1097/MD.0000000000021161

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  42. 特集 薬剤性消化器疾患の診療 4 .その他の薬剤性消化器疾患(4)免疫チェックポイント阻害薬による消化器障害

    伊藤 隆徳, 澤田 つな騎, 中村 正直, 本多 隆, 石上 雅敏, 藤城 光弘

    臨床消化器内科   35 巻 ( 7 ) 頁: 759 - 765   2020年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:日本メディカルセンター  

    DOI: 10.19020/cg.0000001205

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  43. Correlation of serum zinc levels with pathological and laboratory findings in patients with nonalcoholic fatty liver disease.

    Ito T, Ishigami M, Ishizu Y, Kuzuya T, Honda T, Ishikawa T, Toyoda H, Kumada T, Fujishiro M

    European journal of gastroenterology & hepatology   32 巻 ( 6 ) 頁: 748 - 753   2020年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:European Journal of Gastroenterology and Hepatology  

    DOI: 10.1097/MEG.0000000000001587

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  44. Complete response of advanced hepatocellular carcinoma achieved by sorafenib dose re-escalation after failure of long-term low-dose-sorafenib treatment combined with transcatheter arterial chemoembolization: a case report.

    Muto H, Kuzuya T, Ito T, Ishizu Y, Honda T, Ishikawa T, Ishigami M, Fujishiro M

    Clinical journal of gastroenterology   13 巻 ( 3 ) 頁: 397 - 402   2020年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Clinical Journal of Gastroenterology  

    Few reports have described dose re-escalation after long-term low-dose sorafenib leading to good outcomes. Here, we report the case of an 80-year-old woman with advanced hepatocellular carcinoma who achieved complete response from sorafenib dose re-escalation after the failure of long-term low-dose sorafenib treatment combined with transcatheter arterial chemoembolization. Sorafenib therapy was initiated at 400 mg once daily due to old age and low platelet count. 5 months later, this dose was reduced to 200 mg once daily because of adverse events. Best radiological antitumor response by sorafenib treatment alone was judged as stable disease according to the modified Response Evaluation Criteria in Solid Tumors. 1 year later, she showed progressive disease owing to the progression of intrahepatic lesions. She received combination therapy with low-dose sorafenib (200 mg every other day) and transcatheter arterial chemoembolization, which proved relatively effective for three and a half years. Antitumor response by the fourth transcatheter arterial chemoembolization and subsequent low-dose sorafenib was clearly progressive disease. At that time, sorafenib-related adverse events were well-controlled. Sorafenib dose was re-escalated to 200 mg once daily. After this re-escalation, tumor markers declined rapidly, and adverse events remained tolerable. 4 months later, complete response was achieved.

    DOI: 10.1007/s12328-019-01066-7

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  45. Real world data of liver injury induced by immune checkpoint inhibitors in Japanese patients with advanced malignancies.

    Mizuno K, Ito T, Ishigami M, Ishizu Y, Kuzuya T, Honda T, Kawashima H, Inukai Y, Toyoda H, Yokota K, Hase T, Maeda O, Kiyoi H, Nagino M, Hibi H, Kodera Y, Fujimoto Y, Sone M, Gotoh M, Ando Y, Akiyama M, Hasegawa Y, Fujishiro M

    Journal of gastroenterology   55 巻 ( 6 ) 頁: 653 - 661   2020年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Journal of Gastroenterology  

    Background: Liver injury induced by immune checkpoint inhibitors (ICIs) is an immune-related adverse event (irAE) whose incidence has increased with the broader use of ICIs in clinical practice. However, the incidental risk factors of immune-related liver injury are unknown. We investigated the clinical characteristics of immune-related liver injury. Methods: A total of 546 patients treated with ICIs for advanced malignancies between September 2014 and February 2019 were included retrospectively. Factors associated with immune-related liver injury were determined. Results: Immune-related liver injury (≥ Grade 3) occurred in 29 (5.3%) patients (Grade 3, n = 20; Grade 4, n = 8; Grade 5, n = 1) during the follow-up period (median 153 days). The patterns of liver injuries were hepatocellular, n = 6 (20.7%); cholestatic, n = 17 (58.6%); and mixed, n = 6 (20.7%). The median period between the initial administration of ICIs and the incidence of irAEs was 52 days. Of 29 patients with immune-related liver injury (≥ Grade 3), four showed immune-related cholangitis with non-obstructive dilation of the bile ducts. Factors that were significantly associated with the incidence of immune-related liver injury in multivariate analysis were use of ipilimumab, anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) agent [hazard ratio [HR] 4.22, 95% confidence interval (CI) 1.65–10.80, P = 0.003], and fever over 38 °C within 24 h of initial ICI administration (HR 6.21, 95% CI 2.68–14.40, P < 0.001). Conclusions: We found that the use of ipilimumab and the presence of fever within 24 h of initial ICI administration were predictive factors for immune-related liver injury.

    DOI: 10.1007/s00535-020-01677-9

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  46. Initial Experience of Ramucirumab Treatment After Lenvatinib Failure for Patients With Advanced Hepatocellular Carcinoma.

    Kuzuya T, Ishigami M, Ito T, Ishizu Y, Honda T, Ishikawa T, Fujishiro M

    Anticancer research   40 巻 ( 4 ) 頁: 2089 - 2093   2020年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Anticancer Research  

    Background/Aim: The outcomes of ramucirumab after lenvatinib failure for hepatocellular carcinoma (HCC) patients with alpha fetoprotein (AFP) levels of ≥400 ng/ml are unknown. Patients and Methods: Of 12 patients treated with ramucirumab after lenvatinib failure, 10 patients were enrolled in this retrospective study. Results: The disease control rate of 80% at 6 weeks and the median time to progression of 3.1 months were the same by both the Response Evaluation Criteria in Solid Tumors (RECIST) and the modified RECIST. AFP reduction was seen in 5 patients at 2 weeks and in 3 patients at 6 weeks. The incidence of grade 3 adverse events was low at 10%. The albumin.bilirubin scores within 6 weeks did not worsen. Conclusion: Ramucirumab might have potential therapeutic efficacy and safety in advanced HCC patients after lenvatinib failure. Further studies are needed to confirm the outcomes of ramucirumab after lenvatinib failure.

    DOI: 10.21873/anticanres.14167

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  47. Serum soluble sialic acid-binding immunoglobulin-like lectin-7 concentration as an indicator of liver macrophage activation and advanced fibrosis in patients with non-alcoholic fatty liver disease.

    Sakamoto Y, Yoshio S, Doi H, Kawai H, Shimagaki T, Mori T, Matsuda M, Aoki Y, Osawa Y, Yoshida Y, Arai T, Itokawa N, Ito T, Seko Y, Yamaguchi K, Itoh Y, Mise Y, Saiura A, Taketomi A, Kanto T

    Hepatology research : the official journal of the Japan Society of Hepatology   50 巻 ( 4 ) 頁: 466 - 477   2020年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Hepatology Research  

    Aim: Non-alcoholic fatty liver disease (NAFLD) is a leading cause of liver disease worldwide. Because liver fibrosis is associated with the long-term prognosis of patients with NAFLD, there is an urgent need for non-invasive markers of liver fibrosis. Sialic acid-binding immunoglobulin-like lectin-7 (Siglec-7) is an immunomodulatory molecule expressed on various immune cells, including macrophages, which plays a key role in liver inflammation and fibrosis in NAFLD. We aimed to determine whether serum levels of soluble Siglec-7 (sSiglec-7) could have utility at a marker of fibrosis in this patient population. Methods: We examined serum samples from 93 NAFLD patients and 19 healthy donors for macrophage-associated protein, including sSiglec-7, soluble CD163, and YKL-40, and examined their correlation with liver fibrosis scores, tissue elastography, and histological findings. Independent factors associated with advanced fibrosis were analyzed using a logistic regression model and a decision tree. To clarify the source of sSiglec-7, we examined its expression in liver tissue-derived macrophages and cultured monocyte-derived macrophages. Results: Serum sSiglec-7 levels were significantly higher in NAFLD patients compared with healthy donors, and correlated positively with sCD163 and YKL-40 levels. Serum sSiglec-7 was an independent diagnostic marker with high specificity (96.3%) for advanced fibrosis (F3 and F4) in NAFLD patients. Siglec-7 was mainly expressed on CCR2+ macrophages in the liver, and sSiglec-7 production by monocyte-derived macrophages in vitro was increased after stimulation by pro-inflammatory factors. Conclusions: Elevated serum sSiglec-7 could serve as an independent marker with high specificity for advanced liver fibrosis in patients with NAFLD.

    DOI: 10.1111/hepr.13464

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  48. Sorafenib <i>vs</i>. Lenvatinib as First-line Therapy for Advanced Hepatocellular Carcinoma With Portal Vein Tumor Thrombosis.

    Kuzuya T, Ishigami M, Ito T, Ishizu Y, Honda T, Ishikawa T, Fujishiro M

    Anticancer research   40 巻 ( 4 ) 頁: 2283 - 2290   2020年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Anticancer Research  

    Background/Aim: We aimed to compare the outcomes between sorafenib and lenvatinib as first-line therapy for advanced hepatocellular carcinoma (HCC) with major portal vein tumor thrombosis (Vp3/4). Patients and Methods: This retrospective study enrolled 41 HCC patients with Vp3/4 and Child-Pugh A. Results: The outcomes in the lenvatinib group (n=13) were significantly better than those in the sorafenib group (n=28) [best objective response rate according to the modified Response Evaluation Criteria in Solid Tumors: 53.8% vs. 14.3%; p=0.0193, best disease control rate: 92.3% vs. 35.7%; p=0.0008, median overall survival (OS): not reached vs. 187 days; p=0.0040, respectively]. Lenvatinib treatment was the only significant predictor of better OS and time to tumor progression. No patient needed to discontinue lenvatinib treatment due to drug-related adverse events. Conclusion: Compared with sorafenib, lenvatinib treatment for advanced HCC with Vp3/4 may lead to more favorable outcomes.

    DOI: 10.21873/anticanres.14193

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  49. Dynamic Evaluation of Liver Fibrosis to Assess the Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis C Who Achieved Sustained Virologic Response.

    Toyoda H, Tada T, Yasuda S, Mizuno K, Ito T, Kumada T

    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America   70 巻 ( 6 ) 頁: 1208 - 1214   2020年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1093/cid/ciz359

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  50. Favorable radiological antitumor response at 2 weeks after starting lenvatinib for patients with advanced hepatocellular carcinoma.

    Kuzuya T, Ishigami M, Ito T, Ishizu Y, Honda T, Ishikawa T, Fujishiro M

    Hepatology research : the official journal of the Japan Society of Hepatology   50 巻 ( 3 ) 頁: 374 - 381   2020年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Hepatology Research  

    Aim: We aimed to investigate the radiological antitumor response at 2 weeks after starting lenvatinib for patients with advanced hepatocellular carcinoma in real-world practice. Methods: This retrospective study enrolled 40 patients who received lenvatinib. Radiological antitumor response was evaluated according to the modified Response Evaluation Criteria in Solid Tumors. Results: The objective response rate at 2 weeks and best overall response on confirmation of complete response, partial response (PR), and stable disease required (confirmed response) were 57.5% and 32.5%, respectively. Based on confirmed response, the overall survival rate was significantly longer in patients with an objective response rate than in those with stable disease or progressive disease after 12 months (73.2% and 54.2%, P = 0.0358). All 13 patients with an objective response rate on confirmed response were evaluated as PR at 2 weeks. The alpha-fetoprotein ratio at 2 weeks was a significant factor associated with PR of response rate at 2 weeks. The median relative dose intensity from 2 to 6 weeks was significantly lower than that from 0 to 2 weeks (69.6% vs. 100%, P < 0.0001). Stratified by the antitumor response at 6 weeks considering the image evaluation at 2 weeks, the median relative dose intensity from 2 to 6 weeks was significantly lower in patients with progressive disease than in those with PR or stable disease (45.2% vs. 72.6%, P = 0.0482). Conclusions: The radiological antitumor response at 2 weeks was favorable. Information on a favorable visible therapeutic response very early after lenvatinib initiation can help patients maintain their motivation for treatment, and allow physicians to continue treatment effectively and safely.

    DOI: 10.1111/hepr.13452

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  51. Relationship Between Adverse Events and Microbiomes in Advanced Hepatocellular Carcinoma Patients Treated With Sorafenib.

    Yamamoto K, Kuzuya T, Honda T, Ito T, Ishizu Y, Nakamura M, Miyahara R, Kawashima H, Ishigami M, Fujishiro M

    Anticancer research   40 巻 ( 2 ) 頁: 665 - 676   2020年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Anticancer Research  

    DOI: 10.21873/anticanres.13996

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  52. Effect of weight change and lifestyle modifications on the development or remission of nonalcoholic fatty liver disease: sex-specific analysis.

    Yoshioka N, Ishigami M, Watanabe Y, Sumi H, Doisaki M, Yamaguchi T, Ito T, Ishizu Y, Kuzuya T, Honda T, Ishikawa T, Haruta JI, Fujishiro M

    Scientific reports   10 巻 ( 1 ) 頁: 481   2020年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Scientific Reports  

    The effects of changes in various lifestyle habits on nonalcoholic fatty liver disease (NAFLD) have not been well elucidated. We aimed to clarify how weight change and lifestyle modifications were associated with the development or remission of NAFLD. In this longitudinal cohort study, we reviewed the periodic health checkup data of 1,421 subjects with no causes of liver disease besides NAFLD who had received at least two health checkups between 2009 and 2018. The prevalence of NAFLD at baseline was 34.1% (484/1,421). During follow-up period (4.6 ± 2.8 years), 104 subjects developed NAFLD and 127 subjects demonstrated NAFLD remission. The frequency of NAFLD development or that of NAFLD remission significantly increased as the larger weight gain or weight loss was, respectively (both, p < 0.001). Approximately 40% of the subjects who maintained ≥ 1%/year weight loss achieved NAFLD remission. By multivariate analysis, quitting smoking were independently associated with NAFLD development (adjusted odds ratio [AOR], 2.86; 95% CI, 1.24–6.62). Subjects who quit smoking demonstrated large weight gain (≥1%/year) significantly more frequently than the other subjects (p < 0.001). In sex-specific analysis, starting to exercise was independently associated with NAFLD remission in men (AOR, 2.38; 95% CI, 1.25–4.53).

    DOI: 10.1038/s41598-019-57369-9

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  53. Rapid increase of platelet counts during antiviral therapy in patients with hepatitis C virus infection.

    Ishizu Y, Ishigami M, Hayashi K, Honda T, Kuzuya T, Ito T, Fujishiro M

    Hepatology research : the official journal of the Japan Society of Hepatology   50 巻 ( 1 ) 頁: 47 - 56   2020年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Hepatology Research  

    DOI: 10.1111/hepr.13426

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  54. Efficacy and Safety of Sorafenib in Unresectable Hepatocellular Carcinoma with Bile Duct Invasion.

    Tanaka T, Kuzuya T, Ishigami M, Ito T, Ishizu Y, Honda T, Ishikawa T, Fujishiro M

    Oncology   98 巻 ( 9 ) 頁: 621 - 629   2020年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Oncology (Switzerland)  

    Because the frequency of bile duct invasion in hepatocellular carcinoma (HCC) patients is very rare, there is limited clinical evidence to demonstrate the outcomes of systemic therapy in HCC with bile duct invasion. Our aim was to clarify the efficacy and safety of sorafenib treatment in patients with unresectable advanced HCC with bile duct invasion. Methods: One hundred and seventy-five patients with advanced HCC were enrolled in this study. We retrospectively compared the outcomes of sorafenib between patients without bile duct invasion [B (-) group, n = 165] and those with bile duct invasion [B (+) group, n = 10]. Results: There were no significant differences in the confirmed objective response rate (ORR) and the confirmed disease control (DC) rate between the B (-) and the B (+) groups (13.9 vs. 20.0%, p = 0.637 for ORR; 47.2 vs. 70.0%, p = 0.202 for DC rate, respectively). There were no significant differences in median overall survival (OS) and time to progression (TTP) between the B (-) group and the B (+) group (14.8 vs. 14.1 months, p = 0.780 for OS; 3.4 vs. 5.7 months, p = 0.277 for TTP, respectively). Post-treatment factors associated with good OS were changes in albumin-bilirubin score (0-6 weeks) of <0.25, and antitumor response at 6 weeks of DC. Though 5 of 10 patients (50%) in the B (+) group had bile duct complications, such as obstructive jaundice and biliary bleeding, these 5 patients were able to recover from biliary troubles by careful and vigorous management with biliary endoscopic intervention, and were able to continue sorafenib therapy safely. Conclusions: Our present results suggest that sorafenib might have potential therapeutic efficacy and safety in advanced HCC patients with bile duct invasion. In case of biliary tract troubles before and during sorafenib treatment, early biliary management may be important to continue sorafenib therapy safely. Further studies are needed to confirm the outcomes of sorafenib in advanced HCC patients with bile duct invasion.

    DOI: 10.1159/000507051

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  55. Serum Nutritional Markers as Prognostic Factors for Hepatic and Extrahepatic Carcinogenesis in Japanese Patients with Nonalcoholic Fatty Liver Disease.

    Ito T, Ishigami M, Ishizu Y, Kuzuya T, Honda T, Ishikawa T, Toyoda H, Kumada T, Fujishiro M

    Nutrition and cancer   72 巻 ( 5 ) 頁: 884 - 891   2020年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Nutrition and Cancer  

    Serum zinc (Zn) levels and the branched chain amino acid/tyrosine molar ratio (BTR) were reported to decrease with the progression of various chronic liver diseases. We investigated the impact of BTR and Zn on the incidence of malignancies in patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD). A total of 179 Japanese NAFLD patients who underwent liver biopsy were enrolled. Hepatocellular carcinoma (HCC) and extrahepatic malignancies developed in 7 (3.9%) and 10 (5.6%) patients, respectively, during the follow-up period (median 7.9 years). Patients with low BTR levels (<5.0) and Zn deficiency (<70 μg/dL) had significantly higher incidences of HCC and extrahepatic malignancies (P < 0.001 and 0.026), respectively. Multiple logistic regression analyses revealed the following risk factors: liver fibrosis (F3–4) (hazard ratio [HR] 24.292, 95% confidence interval [CI] 2.802–210.621, P = 0.004) and BTR < 5.0 (HR 5.462, 95% CI 1.095–27.253, P = 0.038) for HCC, and serum Zn level <70 μg/dL (HR 3.504, 95% CI 1.010–12.157, P = 0.048) and liver inflammation (A2–3) (HR 3.445, 95% CI 0.886–13.395, P = 0.074) for extra-hepatic malignancies. In conclusion, serum BTR and Zn levels were useful for predicting HCC and extrahepatic malignancies in NAFLD, respectively.

    DOI: 10.1080/01635581.2019.1653474

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  56. Sarcopenia impairs health-related quality of life in cirrhotic patients.

    Ando Y, Ishigami M, Ito T, Ishizu Y, Kuzuya T, Honda T, Ishikawa T, Fujishiro M

    European journal of gastroenterology & hepatology   31 巻 ( 12 ) 頁: 1550 - 1556   2019年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:European Journal of Gastroenterology and Hepatology  

    DOI: 10.1097/MEG.0000000000001472

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  57. Successful Treatment of Hepatocellular Carcinoma with Regorafenib after Sorafenib-induced Hypersensitivity.

    Yoshioka N, Kuzuya T, Ito T, Ishizu Y, Honda T, Ishikawa T, Ishigami M, Fujishiro M

    Internal medicine (Tokyo, Japan)   58 巻 ( 19 ) 頁: 2803 - 2808   2019年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:一般社団法人 日本内科学会  

    <p>Sorafenib and regorafenib are tyrosine kinase inhibitors that are used in the treatment of hepatocellular carcinoma and which have similar chemical structures and toxicity profiles. We herein report a case in which regorafenib treatment could be continued for 10 months and stable disease could be maintained for a long period despite the discontinuation of sorafenib due to grade 4 liver injury and grade 3 fever. The severe adverse events could be attributed to drug hypersensitivity, since a drug-induced lymphocyte stimulation test (DLST) indicated sensitivity to sorafenib. A DLST for regorafenib was negative. This is the first report showing that regorafenib could be safely administered after the discontinuation of sorafenib due to hypersensitivity. </p>

    DOI: 10.2169/internalmedicine.2812-19

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  58. CHANGES OF MICROBIOTA AFTER HEPATITIS C VIRUS ERADICATION

    Honda Takashi, Ishigami Masatoshi, Yamamoto Kenta, Ito Takanori, Ishizu Yoji, Kuzuya Teiji, Fujishiro Mitsuhiro

    HEPATOLOGY   70 巻   頁: 1160A - 1161A   2019年10月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  59. 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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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  60. INDICATION FOR HCC TREATMENT IN RECENT ERA-PROPOSAL OF THE NEW PRIORITY FOR LIVER TRANSPLANTATION IN PATIENTS WITH HCC

    Ishigami Masatoshi, Honda Takashi, Kuzuya Teiji, Ishizu Yoji, Ito Takanori, Fujishiro Mitsuhiro

    HEPATOLOGY   70 巻   頁: 543A - 544A   2019年10月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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

    Yokoyama S, Ishigami M, Honda T, Kuzuya T, Ishizu Y, Ito T, Hirooka Y, Tanaka Y, Tainaka T, Shirota C, Chiba K, Uchida H, Fujishiro M

    Hepatology research : the official journal of the Japan Society of Hepatology   49 巻 ( 10 ) 頁: 1162 - 1168   2019年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Hepatology Research  

    DOI: 10.1111/hepr.13381

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  62. UTILITY OF THE ALBUMIN-BILIRUBIN SCORE FOR PREDICTING PROGNOSIS IN JAPANESE PATIENTS WITH PRIMARY BILIARY CHOLANGITIS: AN ANALYSIS USING TIME-DEPENDENT RECEIVER OPERATING CHARACTERISTICS

    Ito Takanori, Ishigami Masatoshi, Ishizu Yoji, Kuzuya Teiji, Honda Takashi, Yasuda Satoshi, Toyoda Hidenori, Kumada Takashi, Fujishiro Mitsuhiro

    HEPATOLOGY   70 巻   頁: 789A - 790A   2019年10月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  63. Clinical characteristics and outcomes of candidates for second-line therapy, including regorafenib and ramucirumab, for advanced hepatocellular carcinoma after sorafenib treatment.

    Kuzuya T, Ishigami M, Ito T, Ishizu Y, Honda T, Ishikawa T, Hirooka Y, Fujishiro M

    Hepatology research : the official journal of the Japan Society of Hepatology   49 巻 ( 9 ) 頁: 1054 - 1065   2019年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Hepatology Research  

    DOI: 10.1111/hepr.13358

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  64. The relationship between portal hypertension and the microbiome

    Yamamoto K., Honda T., Hattori S., Pu L. Zorron Cheng Tao, Ito T., Yamamura T., Ishizu Y., Kuzuya T., Ishigami M., Fujishiro M.

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY   34 巻   頁: 106 - 107   2019年9月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  65. Association between core mutations and annual decline rate of HBVDNA and HBsAg in chronic hepatitis B patients treated with nucleoside analogue

    Honda Takashi, Ishigami Masatoshi, Ito Takanori, Ishizu Yoji, Kuzuya Teiji, Fujishiro Mitsuhiro

    JOURNAL OF HEPATOLOGY   70 巻 ( 1 ) 頁: E258 - E258   2019年4月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  66. Association between gut microbiota and hepatocellular carcinoma in patients with chronic liver disease

    Honda Takashi, Ishigami Masatoshi, Yamamoto Kenta, Ito Takanori, Ishizu Yoji, Kuzuya Teiji, Fujishiro Mitsuhiro

    JOURNAL OF HEPATOLOGY   70 巻 ( 1 ) 頁: E512 - E513   2019年4月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  67. Serum Zinc levels as a prognostic factor for extra-hepatic carcinogenesis in Japanese patients with non-alcoholic liver disease

    Ito Takanori, Ishigami Masatoshi, Ishizu Yoji, Kuzuya Teiji, Honda Takashi, Fujishiro Mitsuhiro

    JOURNAL OF HEPATOLOGY   70 巻 ( 1 ) 頁: E298 - E298   2019年4月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  68. The optimal cut-off points of FIB-4 index for predicting the incidences of HCC and extra-hepatic malignancies in biopsyproven Japanese NAFLD patients

    Ito Takanori, Ishigami Masatoshi, Ishizu Yoji, Kuzuya Teiji, Honda Takashi, Fujishiro Mitsuhiro

    JOURNAL OF HEPATOLOGY   70 巻 ( 1 ) 頁: E775 - E775   2019年4月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  69. The early clinical response at 2 weeks of lenvatinib therapy for patients with advanced HCC

    Kuzuya Teiji, Ishigami Masatoshi, Ito Takanori, Ishizu Yoji, Honda Takashi, Fujishiro Mitsuhiro

    JOURNAL OF HEPATOLOGY   70 巻 ( 1 ) 頁: E611 - E611   2019年4月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  70. Influence of proton pump inhibitors on microbiota in chronic liver disease patients.

    Yamamoto K, Ishigami M, Honda T, Takeyama T, Ito T, Ishizu Y, Kuzuya T, Hayashi K, Goto H, Hirooka Y

    Hepatology international   13 巻 ( 2 ) 頁: 234 - 244   2019年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/s12072-019-09932-9

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  71. Utility and limitations of noninvasive fibrosis markers for predicting prognosis in biopsy-proven Japanese non-alcoholic fatty liver disease patients.

    Ito T, Ishigami M, Ishizu Y, Kuzuya T, Honda T, Hayashi K, Nishimura D, Toyoda H, Kumada T, Goto H, Hirooka Y

    Journal of gastroenterology and hepatology   34 巻 ( 1 ) 頁: 207 - 214   2019年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Journal of Gastroenterology and Hepatology (Australia)  

    DOI: 10.1111/jgh.14448

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  72. Association between Core Mutations Induced By Interferon Therapy and Annual Decline Rate of Hbvdna in Chronic Hepatitis B Patients

    Honda Takashi, Ishigami Masatoshi, Ito Takanori, Ishizu Yoji, Kuzuya Teiji, Hirooka Yoshiki

    HEPATOLOGY   68 巻   頁: 1233A-1234A   2018年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  73. Interferon-Free Antiviral Therapy Rapidly Improves Thrombocytopenia in Patients with Advanced Chronic Hepatitis C

    Ishizu Yoji, Ishigami Masatoshi, Ito Takanori, Kuzuya Teiji, Honda Takashi, Hirooka Yoshiki

    HEPATOLOGY   68 巻   頁: 1157A-1158A   2018年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  74. Comparison of Gut Microbiota and Predicted Functional Metagenome in Hepatitis C Patients with and without Advanced Fibrosis Categorized By FIB4-Index

    Yamamoto Kenta, Ishigami Masatoshi, Ito Takanori, Ishizu Yoji, Kuzuya Teiji, Honda Takashi, Hirooka Yoshiki

    HEPATOLOGY   68 巻   頁: 590A-590A   2018年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  75. Successful treatment of esophageal bleeding due to rupture of major aortopulmonary collateral arteries by transcatheter arterial embolization. 査読有り

    Ito T, Ishigami M, Ishizu Y, Kuzuya T, Honda T, Matsushima M, Kato T, Hirooka Y

    Clinical journal of gastroenterology     2018年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/s12328-018-0895-8

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  76. Secreted ectodomain of SIGLEC-9 and MCP-1 ameliorate acute liver failure in rats by altering bone marrow macrophage polarity

    Ito T., Ishigami M., Yamamoto A., Ishizu Y., Kazuya T., Honda T., Hayashi K., Ishikawa T., Hirooka Y., Goto H.

    JOURNAL OF HEPATOLOGY   68 巻   頁: S614-S614   2018年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  77. Utility and limitation of non-invasive fibrosis markers for predicting the prognosis in biopsy-proven Japanese NAFLD patients

    Ito T., Ishigami M., Ishizu Y., Kazuya T., Honda T., Hayashi K., Ishikawa T., Hirooka Y., Goto H.

    JOURNAL OF HEPATOLOGY   68 巻   頁: S561-S561   2018年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  78. Secreted Ectodomain of SIGLEC-9 and MCP-1 Synergistically Improve Acute Liver Failure in Rats by Altering Macrophage Polarity.

    Ito T, Ishigami M, Matsushita Y, Hirata M, Matsubara K, Ishikawa T, Hibi H, Ueda M, Hirooka Y, Goto H, Yamamoto A

    Scientific reports   7 巻   頁: 44043   2017年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/srep44043

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  79. Ability of Cytokeratin-18 Fragments and FIB-4 Index to Diagnose Overall and Mild Fibrosis Nonalcoholic Steatohepatitis in Japanese Nonalcoholic Fatty Liver Disease Patients.

    Kobayashi N, Kumada T, Toyoda H, Tada T, Ito T, Kage M, Okanoue T, Kudo M

    Digestive diseases (Basel, Switzerland)   35 巻 ( 6 ) 頁: 521-530   2017年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1159/000480142

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  80. Multifaceted Therapeutic Benefits of Factors Derived From Dental Pulp Stem Cells for Mouse Liver Fibrosis. 査読有り

    Hirata M, Ishigami M, Matsushita Y, Ito T, Hattori H, Hibi H, Goto H, Ueda M, Yamamoto A

    Stem cells translational medicine   5 巻 ( 10 ) 頁: 1416-1424   2016年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.5966/sctm.2015-0353

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  81. Secreted Ectodomain of Sialic Acid-Binding Ig-Like Lectin-9 and Monocyte Chemoattractant Protein-1 identified from Dental Pulp Stem Cells Synergistically Resolve Acute Liver Failure in Rats by Altering Macrophage Polarity

    Ito Takanori, Yamamoto Akihito, Ishizu Yoji, Kuzuya Teiji, Honda Takashi, Ishikawa Tetsuya, Ishigami Masatoshi, Hirooka Yoshiki, Goto Hidemi

    HEPATOLOGY   64 巻   頁: 515A-515A   2016年10月

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  82. Extra-hepatic feeding arteries of hepatocellular carcinoma: An investigation based on intra-arterial CT aortography images using an angio-MDCT system. 査読有り

    Takada K, Ito T, Kumada T, Toyoda H, Tada T, Sone Y, Endo T, Tanaka K, Kitagawa H, Ichikawa K

    European journal of radiology   85 巻 ( 8 ) 頁: 1400-6   2016年8月

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    DOI: 10.1016/j.ejrad.2016.05.007

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  83. Accurate and rapid identification of feeding arteries with multidetector-row angiography-assisted computed tomography for transarterial chemoembolization for hepatocellular carcinoma. 査読有り

    Takada K, Toyoda H, Tada T, Ito T, Hasegawa R, Gotoh T, Ichikawa H, Sone Y, Kumada T

    Journal of gastroenterology   50 巻 ( 12 ) 頁: 1190-6   2015年12月

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    DOI: 10.1007/s00535-015-1065-0

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  84. Utility of Contrast-enhanced Ultrasonography with Perflubutane for Determining Histologic Grade in Hepatocellular Carcinoma. 査読有り

    Tada T, Kumada T, Toyoda H, Ito T, Sone Y, Kaneoka Y, Maeda A, Okuda S, Otobe K, Takahashi K

    Ultrasound in medicine & biology   41 巻 ( 12 ) 頁: 3070-8   2015年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.ultrasmedbio.2015.07.023

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  85. Utility of the FIB-4 Index for hepatocarcinogenesis in hepatitis C virus carriers with normal alanine aminotransferase levels. 査読有り

    Ito T, Kumada T, Toyoda H, Tada T, Kiriyama S, Tanikawa M, Hisanaga Y, Kanamori A, Kitabatake S

    Journal of viral hepatitis   22 巻 ( 10 ) 頁: 777-83   2015年10月

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    DOI: 10.1111/jvh.12389

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  86. Utility of real-time shear wave elastography for assessing liver fibrosis in patients with chronic hepatitis C infection without cirrhosis: Comparison of liver fibrosis indices. 査読有り

    Tada T, Kumada T, Toyoda H, Ito T, Sone Y, Okuda S, Tsuji N, Imayoshi Y, Yasuda E

    Hepatology research : the official journal of the Japan Society of Hepatology   45 巻 ( 10 ) 頁: E122-9   2015年10月

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    DOI: 10.1111/hepr.12476

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  87. Long-term prognosis of patients with hepatitis B infection: causes of death and utility of nucleos(t)ide analogue therapy. 査読有り

    Tada T, Kumada T, Toyoda H, Kiriyama S, Tanikawa M, Hisanaga Y, Kanamori A, Kitabtake S, Ito T

    Journal of gastroenterology   50 巻 ( 7 ) 頁: 795-804   2015年7月

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    DOI: 10.1007/s00535-014-1011-6

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  88. Risk factors of hepatocellular carcinoma development in non-cirrhotic patients with sustained virologic response for chronic hepatitis C virus infection. 査読有り

    Toyoda H, Kumada T, Tada T, Kiriyama S, Tanikawa M, Hisanaga Y, Kanamori A, Kitabatake S, Ito T

    Journal of gastroenterology and hepatology   30 巻 ( 7 ) 頁: 1183-9   2015年7月

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    DOI: 10.1111/jgh.12915

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  89. FIB-4 index for assessing the prognosis of hepatocellular carcinoma in patients with Child-Pugh class A liver function. 査読有り

    Ito T, Kumada T, Toyoda H, Tada T

    Journal of cancer research and clinical oncology   141 巻 ( 7 ) 頁: 1311-9   2015年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/s00432-015-1922-5

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  90. Diagnostic accuracy for macroscopic classification of nodular hepatocellular carcinoma: comparison of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging and angiography-assisted computed tomography. 査読有り

    Tada T, Kumada T, Toyoda H, Ito T, Sone Y, Okuda S, Ogawa S, Igura T, Imai Y

    Journal of gastroenterology   50 巻 ( 1 ) 頁: 85-94   2015年1月

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    DOI: 10.1007/s00535-014-0947-x

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  91. Utility of contrast-enhanced ultrasound with perflubutane for diagnosing the macroscopic type of small nodular hepatocellular carcinomas. 査読有り

    Tada T, Kumada T, Toyoda H, Ito T, Sone Y, Kaneoka Y, Maeda A, Okuda S, Otobe K, Takahashi K

    European radiology   24 巻 ( 9 ) 頁: 2157-66   2014年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/s00330-014-3254-2

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  92. Changes in highly sensitive alpha-fetoprotein for the prediction of the outcome in patients with hepatocellular carcinoma after hepatectomy. 査読有り

    Toyoda H, Kumada T, Tada T, Ito T, Maeda A, Kaneoka Y, Kagebayashi C, Satomura S

    Cancer medicine   3 巻 ( 3 ) 頁: 643-51   2014年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1002/cam4.218

    PubMed

  93. Oral supplementation with branched-chain amino acid granules prevents hepatocarcinogenesis in patients with hepatitis C-related cirrhosis: A propensity score analysis.

    Tada T, Kumada T, Toyoda H, Kiriyama S, Tanikawa M, Hisanaga Y, Kanamori A, Kitabatake S, Niinomi T, Ito T, Hasegawa R, Ando Y, Yamamoto K, Tanaka T

    Hepatology research : the official journal of the Japan Society of Hepatology   44 巻 ( 3 ) 頁: 288-95   2014年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/hepr.12120

    PubMed

  94. [An autopsy of G-CSF-producing anaplastic carcinoma of the pancreas with impaired accumulation on FDG-PET after S-1 chemotherapy].

    Ikeda S, Okubo K, Shibahara H, Narita M, Morita K, Takeuchi A, Kanazawa H, Ito T, Nishimura D, Katada N

    Gan to kagaku ryoho. Cancer & chemotherapy   40 巻 ( 6 ) 頁: 789-92   2013年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    PubMed

  95. Non-hypervascular hypointense nodules detected by Gd-EOB-DTPA-enhanced MRI are a risk factor for recurrence of HCC after hepatectomy.

    Toyoda H, Kumada T, Tada T, Niinomi T, Ito T, Sone Y, Kaneoka Y, Maeda A

    Journal of hepatology   58 巻 ( 6 ) 頁: 1174-80   2013年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.jhep.2013.01.030

    PubMed

  96. テガフール・ウラシル配合剤が著効したB型肝炎合併 granulocyte colony-stimulating factor 産生肝細胞癌の1例

    伊藤 隆徳, 大久保 賢治, 塩見 正哉, 成田 道彦, 森田 清, 竹内 淳史, 金沢 宏信, 清水 潤一, 竹山 友章, 橋詰 清孝, 柴原 弘明, 西村 大作, 片田 直幸, 片野 義明, 後藤 秀実

    日本消化器病學會雜誌 = The Japanese journal of gastro-enterology   109 巻 ( 12 ) 頁: 2088-2096   2012年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    症例は37歳,男性.B型肝炎に合併したG-CSF産生肝細胞癌に対して右葉切除術を行った.しかし術後2カ月で肺転移を認め,ソラフェニブ内服を開始したが更に肺転移増大を認めた.UFT内服に変更としたところ肺転移の著明な縮小を認めた.診断後2年経過した現在も外来加療継続中である.G-CSF産生肝細胞癌は極めてまれで,テガフール・ウラシル配合剤が著効した報告はなく貴重な症例と考えられた.<br>

    DOI: 10.11405/nisshoshi.109.2088

  97. [A case of successful treatment of granulocyte colony-stimulating factor producing hepatocellular carcinoma accompanying type B hepatitis with tegafur-uracil].

    Ito T, Okubo K, Shiomi M, Narita M, Morita K, Takeuchi A, Kanazawa H, Shimizu J, Takeyama T, Hashizume K, Shibahara H, Nishimura D, Katada N, Katano Y, Goto H

    Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology   109 巻 ( 12 ) 頁: 2088-96   2012年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    PubMed

  98. A case of successful treatment of granulocyte colony-stimulating factor producing hepatocellular carcinoma accompanying type B hepatitis with tegafur-uracil

    Ito T.

    Journal of Japanese Society of Gastroenterology   109 巻 ( 12 ) 頁: 2088-2096   2012年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Scopus

  99. Prognostic significance of a combination of pre- and post-treatment tumor markers for hepatocellular carcinoma curatively treated with hepatectomy.

    Toyoda H, Kumada T, Tada T, Niinomi T, Ito T, Kaneoka Y, Maeda A

    Journal of hepatology   57 巻 ( 6 ) 頁: 1251-7   2012年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.jhep.2012.07.018

    PubMed

  100. [Low-dose mirtazapine improved nausea and appetite loss during S-1 therapy].

    Shibahara H, Ito T, Uematsu N, Imai E, Nishimura D

    Gan to kagaku ryoho. Cancer & chemotherapy   39 巻 ( 1 ) 頁: 143-5   2012年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    PubMed

▼全件表示

科研費 1

  1. 歯髄幹細胞産生因子による腸肝臓器相関に着目した新規NASH治療法の開発

    研究課題/研究課題番号:19K17457  2019年4月 - 2022年3月

    科学研究費助成事業  若手研究

    伊藤 隆徳

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    担当区分:研究代表者 

    配分額:4160000円 ( 直接経費:3200000円 、 間接経費:960000円 )

    現在、非アルコール性脂肪性肝炎(NASH)に対しての基礎研究や治験薬の開発が国内外を問わず行われているが、肝硬変に至った場合、その治療法は確立されていない。われわれはヒト乳歯歯髄幹細胞が産生する抗炎症・再生因子をNASHモデルに投与し、重要な免疫細胞の一つであるマクロファージを調節することで、脂肪・炎症・線維化を抑制しNASH進展を抑制することができるかどうかの検討を行う。さらにNASHの原因のひとつとされる腸内環境にも注目し、詳細なメカニズム解析を行うことで、将来の治療応用を見据えた基礎データを取得したいと考える。
    本年度は、本研究2年目に当たり、申請書記載の「研究実施予定」に従って、1) in vitro系におけるSHED-CMの治療効果、2) 非アルコール性脂肪肝炎(NASH)モデルのin vivoにおける腸管循環に着目したメカニズム解析を中心に検討・解析した。
    初年度にウェスタンダイエット食と高濃度糖水、週1の少量四塩化炭素腹腔内投与を用いたヒトNASH類似肝線維化マウスモデルに対して、SHED-CMが抗炎症・線維化抑制効果を示すことがわかっていた。具体的にはSHED-CM治療群における血清トランスアミナーゼの改善、中性脂肪・遊離脂肪酸の低下、また肝組織におけるα-SMA陽性線維化面積の有意な減少を認めた。しかしながら今回追加検討にて、NAFLD Activity Score(NAS)における炎症因子は改善あるものの、脂肪沈着の程度には変化を認めなかった。つまり、SHED-CM治療は肝内脂肪代謝には関与せずに抗炎症・線維化抑制効果を示していると考えられた。
    続いてNASH発症の原因の一つと考えられている腸肝相関を検討するために、肝組織におけるLPS受容体TLR4発現、また腸管透過性に関与する遺伝子であるZo-1の回腸末端における発現を解析するとqPCRにおいてSHED-CM群におけるTLR4の有意な発現低下、また蛍光免疫染色においてZo-1陽性細胞の有意な増加を認めた。
    最後にin vitroにおいて腸管透過性へのSHED-CMの効果を検討するために、IFNγ・TNFαを用いてCaco-2細胞のtight junctionを破壊したのちにSHED-CM置換を行い、その影響を検討した。SHED-CM治療群では、Zo-1陽性細胞の増加、ならびにFITC-デキストランを用いた腸管透過性確認試験においても、SHED-CMの透過性維持効果が確認された。
    概ね研究実施予定通りに進んでいる。一部、in vitroにおいて星細胞(Lx-2)のviabilityやTGF-βによる活性化が安定しないため、SHED-CMによる星細胞への影響は検討しきれていない。しかし、SHED-CMのマクロファージを介した肝内炎症・線維化抑制や腸管透過性への影響など、これまでに予定した主なメカニズム解析は完了しており、これまでのデータをまとめて論文化を進めている。
    次年度は、SHED-CM内のどの因子が治療効果発現メカニズムに直接的に関与しているか、特に腸肝相関に焦点を当てて、検討したいと考えている。また腸管透過性に直接的に影響しうる、腸内細菌叢に関してもSHED-CMとコントロール群において、次世代シークエンサーを用いて解析を行う予定である。