Updated on 2024/03/11

写真a

 
IMAI Norihiro
 
Organization
Graduate School of Medicine Program in Integrated Medicine Internal Medicine Assistant Professor
Graduate School
Graduate School of Medicine
Undergraduate School
School of Medicine Department of Medicine
Title
Assistant Professor
External link

Degree 1

  1. Doctor of Philosophy (Medical Science) ( 2016.3   Nagoya University ) 

Professional Memberships 5

  1. 日本内科学会

  2. 日本消化器病学会

  3. 日本消化器内視鏡学会

  4. 日本肝臓学会

  5. American Association for the Study of Liver Diseases

Awards 7

  1. American Heart Association Postdoctoral Fellowship

    2019   American Heart Association  

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  2. Best Poster Award, Postdoc Research Day

    2019   Weill Cornell Medicine, The Postdoctoral Association  

  3. Irwin M. Arias, MD Postdoctoral Research Fellowship Award

    2018   American Liver Foundation  

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    Country:United States

  4. 2015 Best Poster Award, the 120th annual meeting of the Japanese Association of Anatomists

    2015   the 120th Annual Meeting of The Japanese Association of Anatomists, the 92nd Annual Meeting of The Physiological Society of Japan   UBXD8 deletion in hepatocytes induced more evident abnormalities in female than in male mice

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    Award type:Award from Japanese society, conference, symposium, etc.  Country:Japan

  5. Presidential Poster of Distinction

    2015   American Association for the Study of Liver Disease  

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    Award type:Award from international society, conference, symposium, etc.  Country:United States

  6. International Young Investigator Travel Award

    2015   American Association for the Study of Liver Disease  

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    Award type:Award from international society, conference, symposium, etc.  Country:United States

  7. Young Investigator Award of Nagoya University Internal Medicine

    2015  

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    Country:Japan

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Papers 87

  1. A 70-year-old Woman with Asymptomatic Ferroportin Disease

    Ishikawa Tetsuya, Tatsumi Yasuaki, Kato Koichi, Hayashi Yumi, Imai Norihiro, Ito Takanori, Ishizu Youji, Ishigami Masatoshi, Nihei Wataru, Kato Ayako, Hayashi Hisao

    Internal Medicine   Vol. advpub ( 0 )   2024.2

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:The Japanese Society of Internal Medicine  

    <p>A 59-year-old Japanese woman presented with hyperferritinemia. We decided against iron removal treatment because there were no symptoms or signs of iron-induced organ damage. A follow-up study revealed a gradual increase in transferrin saturation. The patient underwent a second examination at 66 years old. A liver biopsy showed substantial iron deposits in hepatocytes and Kupffer cells but no inflammation or fibrosis. Serum hepcidin-25 levels were highly parallel with hyperferritinemia. A genetic analysis revealed a <i>G80S</i> mutation in <i>SLC40A1</i>. These features are compatible with those of ferroportin disease. The patient remained asymptomatic at 70 years old, suggesting that the iron-loading condition may have been benign. </p>

    DOI: 10.2169/internalmedicine.2392-23

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

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

    HEPATOLOGY INTERNATIONAL   Vol. 17 ( 6 ) page: 1378 - 1392   2023.12

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Hepatology International  

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

    DOI: 10.1007/s12072-023-10581-2

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

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

    HEPATOLOGY RESEARCH     2023.10

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Hepatology Research  

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

    DOI: 10.1111/hepr.13976

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  4. CHARACTERISTICS OF GUT MICROBIOTA ASSOCIATED WITH FUNCTIONAL CURE IN CHRONIC HEPATITIS B PATIENTS WITH HBEAG- NEGATIVE; POSSIBLE INHIBITION OF HEPATITIS B VIRUS BY BUTYRATE- PRODUCING BACTERIA

    Honda, T; Murayama, A; Inukai, Y; Muto, H; Yokoyama, S; Yamamoto, K; Ito, T; Imai, N; Ishizu, Y; Ishigami, M; Yoshio, S; Ishikawa, T; Kawashima, H; Kato, T

    HEPATOLOGY   Vol. 78   page: S594 - S594   2023.10

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  5. PREVALENCE OF INTRANUCLEAR LIPID DROPLETS IN NONALCOHOLIC FATTY LIVER DISEASE

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

    HEPATOLOGY   Vol. 78   page: S1125 - S1126   2023.10

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  6. INTESTINAL MICROBIOME ASSOCIATED WITH EFFICACY OF ATEZOLIZUMAB AND BEVACIZUMAB THERAPY FOR HEPATOCELLULAR CARCINOMA

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

    HEPATOLOGY   Vol. 78   page: S1273 - S1273   2023.10

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  7. CLINICAL OUTCOMES OF POROUS GLASS MEMBRANE PUMPING EMULSIFICATION DEVICE IN TRANSARTERIAL CHEMOEMBOLIZATION FOR HEPATOCELLULAR CARCINOMA

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

    HEPATOLOGY   Vol. 78   page: S1814 - S1814   2023.10

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  8. CLINICAL FEATURES AND OUTCOME OF LIVER INJURY INDUCED BY IMMUNE CHECKPOINT INHIBITORS IN PATIENTS WITH ADVANCED MALIGNANCIES

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

    HEPATOLOGY   Vol. 78   page: S636 - S636   2023.10

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

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

    EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY   Vol. 35 ( 10 ) page: 1211 - 1215   2023.10

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:European Journal of Gastroenterology and Hepatology  

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

    DOI: 10.1097/MEG.0000000000002628

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

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

    INVESTIGATIONAL NEW DRUGS   Vol. 41 ( 3 ) page: 512 - 521   2023.6

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Investigational New Drugs  

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

    DOI: 10.1007/s10637-023-01366-3

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  11. Significance of pretreatment alpha-fetoprotein in patients with compensated severe fibrosis after hepatitis C viral eradication

    Ishigami, M; Honda, T; Ishizu, Y; Imai, N; Ito, T; Yamamoto, K; Kawashima, H

    JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES   Vol. 30 ( 6 ) page: 834 - 842   2023.6

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Journal of Hepato-Biliary-Pancreatic Sciences  

    Background: We aimed to investigate the factors associated with improvement of liver functional reserve after sustained virological response using interferon-free, direct-acting antiviral combination treatment in patients with compensated, severe fibrosis. Methods: Between September 2014 and April 2020, 492 patients received direct-acting antiviral combination treatment in our hospital. Among them, 173 patients who had severe fibrosis based on a fibrosis-4 index ≥3.25, showed sustained virological response after treatment. We investigated the dynamic change in albumin-bilirubin score and the baseline factors associated with its improvement, 48 weeks after treatment. Results: The baseline significant factors associated with albumin-bilirubin ≦ −0.5 were lower albumin (HR: 15.625, 95% CI: 4.273–58.824, P <.001), higher hepatitis C virus RNA (HR: 4.995, 95% CI: 1.882–13.260, P =.001), and higher alpha-fetoprotein (HR: 1.033, 95% CI: 1.011–1.055, P =.003). Patients with alpha-fetoprotein ≧10 ng/mL showed significant improvement of albumin-bilirubin score from baseline to 48 weeks after treatment compared to those with alpha-fetoprotein <10 ng/mL (P <.001). Conclusions: Baseline serum alpha-fetoprotein might be a predictive factor for improvement of liver function after sustained virological response in patients with severe fibrosis.

    DOI: 10.1002/jhbp.1309

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

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

    SCIENTIFIC REPORTS   Vol. 13 ( 1 ) page: 6851   2023.4

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Scientific Reports  

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

    DOI: 10.1038/s41598-023-33977-4

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  13. A beta cell subset with enhanced insulin secretion and glucose metabolism is reduced in type 2 diabetes

    Rubio-Navarro, A; Gómez-Banoy, N; Stoll, L; Dündar, F; Mawla, AM; Ma, LK; Cortada, E; Zumbo, P; Li, A; Reiterer, M; Montoya-Oviedo, N; Homan, EA; Imai, N; Gilani, A; Liu, CY; Naji, A; Yang, B; Chong, ACN; Cohen, DE; Chen, SB; Cao, JL; Pitt, GS; Huising, MO; Betel, D; Lo, JC

    NATURE CELL BIOLOGY   Vol. 25 ( 4 ) page: 565 - +   2023.4

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Nature Cell Biology  

    The pancreatic islets are composed of discrete hormone-producing cells that orchestrate systemic glucose homeostasis. Here we identify subsets of beta cells using a single-cell transcriptomic approach. One subset of beta cells marked by high CD63 expression is enriched for the expression of mitochondrial metabolism genes and exhibits higher mitochondrial respiration compared with CD63lo beta cells. Human and murine pseudo-islets derived from CD63hi beta cells demonstrate enhanced glucose-stimulated insulin secretion compared with pseudo-islets from CD63lo beta cells. We show that CD63hi beta cells are diminished in mouse models of and in humans with type 2 diabetes. Finally, transplantation of pseudo-islets generated from CD63hi but not CD63lo beta cells into diabetic mice restores glucose homeostasis. These findings suggest that loss of a specific subset of beta cells may lead to diabetes. Strategies to reconstitute or maintain CD63hi beta cells may represent a potential anti-diabetic therapy.

    DOI: 10.1038/s41556-023-01103-1

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

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

    NUTRIENTS   Vol. 15 ( 6 )   2023.3

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Nutrients  

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

    DOI: 10.3390/nu15061473

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

    Yamamoto, T; Morooka, H; Ito, T; Ishigami, M; Mizuno, K; Yokoyama, S; Yamamoto, K; Imai, N; Ishizu, Y; Honda, T; Yokota, K; Hase, T; Maeda, O; Hashimoto, N; Ando, Y; Akiyama, M; Kawashima, H

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY   Vol. 38 ( 2 ) page: 251 - 258   2023.2

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Journal of Gastroenterology and Hepatology (Australia)  

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

    DOI: 10.1111/jgh.16038

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

    Zhao, M; Ma, LY; Honda, T; Kato, A; Ohshiro, T; Yokoyama, S; Yamamoto, K; Ito, T; Imai, N; Ishizu, Y; Nakamura, M; Kawashima, H; Tsuji, NM; Ishigami, M; Fujishiro, M

    DIGESTIVE DISEASES AND SCIENCES   Vol. 68 ( 1 ) page: 155 - 163   2023.1

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Digestive Diseases and Sciences  

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

    DOI: 10.1007/s10620-022-07489-6

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

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

    PEDIATRICS INTERNATIONAL   Vol. 65 ( 1 ) page: e15454   2023.1

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Pediatrics International  

    Background: Esophagogastric varices (EGVs) may develop as a result of portal hypertension in children with biliary atresia (BA). Although endoscopic injection sclerotherapy (EIS) with ethanolamine oleate (EO) is reported useful for children, risk factors associated with the presence of high-risk EGVs after treatment remain unknown. Methods: The subjects were BA patients under 15 years of age who underwent EO-EIS. We retrospectively reviewed a total of 28 treatment sessions of EGVs with red signs and those larger than F2, which were considered to be at high risk of bleeding. Survival analysis was performed for the presence of high-risk EGVs at the time of follow-up endoscopy as the occurrence of an event. Results: Univariate analysis showed a significantly increased risk of the presence of high-risk EGVs post-EO-EIS in patients with increased liver stiffness (LS) and Mac-2 binding protein glycan isomer (M2BPGi), with hazard ratios of 1.48 and 1.15, respectively. The median presence-free period was significantly shorter in the LS ≥ 2.8 m/s patients than in those with LS <2.8 m/s (189 vs. 266 days). Similarly, the median presence-free period was significantly shorter in patients with M2BPGi ≥ 4.0 than in those with M2BPGi < 4.0 (182 vs. 203 days). The results of multivariate analysis revealed that the risk of the presence of high-risk EGVs was significantly higher only in the high-LS group, with a hazard ratio of 2.76. Conclusions: Increased LS is associated with risk of the presence of high-risk EGVs following EO-EIS in children with BA.

    DOI: 10.1111/ped.15454

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  18. Differences in the Intestinal Microbiome Associated with Diarrhea during Lenvatinib Treatment for Hepatocellular Carcinoma

    Inukai, Y; Yamamoto, K; Honda, T; Ito, T; Imai, N; Ishizu, Y; Nakamura, M; Kawashima, H; Ishigami, M

    DIGESTIVE DISEASES   Vol. 41 ( 1 ) page: 138 - 147   2023.1

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    Introduction: Lenvatinib has been widely used for the treatment of advanced hepatocellular carcinoma (HCC). Some adverse events, including diarrhea, have been reported for lenvatinib. Diarrhea may be associated with the changes in the intestinal microbiome; however, the underlying mechanism has not been elucidated. Aim: In this study, we aimed to investigate the relationship between the intestinal microbiome and diarrhea caused by lenvatinib via analysis of fecal samples collected before treatment. Methods: A total of 21 patients with advanced HCC who were treated with lenvatinib were enrolled. Fecal samples were collected from patients. The patients were divided into diarrhea (n = 8) and nondiarrhea groups (n = 12). We compared the characteristics of patients, incidence of adverse events, composition of the intestinal microbiome, and enrichment of functional pathways between both groups using QIIME2 and PICRUSt2. Results: The median age of the two groups was 73 years. The nondiarrhea group comprised a relatively higher number of male patients than the diarrhea group; however, there were no significant differences in patient characteristics between both groups. The proportion of the microbiome was similar, and alpha and beta diversities were not significantly different between both groups. The relative abundance of order Bacteroidales, including Parabacteroides and Prevotella, was higher in the diarrhea group than in the nondiarrhea group. PICRUSt2 analysis showed some metabolic pathways, including butanoate (butyrate) metabolism, were enriched in the nondiarrhea group when compared with those in the diarrhea group. Conclusion: Differences in the intestinal microbiomes and their functions may influence the incidence of diarrhea during lenvatinib treatment.

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

    Sugiyama, Y; Ishizu, Y; Ando, Y; Yokoyama, S; Yamamoto, K; Ito, T; Imai, N; Nakamura, M; Honda, T; Kawashima, H; Ishikawa, T; Ishigami, M

    HEPATOLOGY RESEARCH   Vol. 52 ( 11 ) page: 937 - 946   2022.11

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    Aim: Conventionally, the skeletal muscle area with computed tomography (CT) attenuation ranging from −29 to +150 Hounsfield unit (HU) divided by height squared (the conventional skeletal muscle index [SMI]) was used as an index of skeletal muscle mass. However, it includes fat-infiltrated skeletal muscle, which is known to have poor function. This study aims to determine whether the low-fat SMI, which uses skeletal muscle mass with CT attenuation ranging from +30 to +150 HU, or conventional SMI appropriately reflects the function of skeletal muscle. Methods: We retrospectively analyzed 120 patients with cirrhosis whose handgrip strength was measured. Among them, 48 patients underwent a physical performance assessment such as liver frailty index (LFI) and short physical performance battery (SPPB), and 80 underwent quality of life (QOL) assessment. The relationships between each SMI and handgrip strength, LFI, SPPB, and QOL were evaluated. Results: Low-fat SMI was significantly correlated with handgrip strength (males, R = 0.393, p = 0.002; females, R = 0.423, p < 0.001) and LFI (males, R = −0.535, p = 0.035; females, R = −0.368, p = 0.039), whereas conventional SMI was not. When using low-fat SMI, patients with low skeletal muscle mass had significantly low handgrip strength, LFI, SPPB, and physical and social-related QOL score than those without. By contrast, no significant differences were found for any items when using conventional SMI. Conclusions: Low-fat SMI is a good index of skeletal muscle mass that appropriately reflects skeletal muscle function.

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

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

    HEPATOLOGY   Vol. 76   page: S1181 - S1181   2022.10

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

    Honda, TH; Ishigami, M; Kato, A; Yokoyama, S; Yamamoto, K; Ito, T; Imai, N; Ishizu, Y; Yasuda, S; Toyoda, H; Kumada, T; Ishikawa, T; Kawashima, H

    HEPATOLOGY   Vol. 76   page: S262 - S263   2022.10

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

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

    HEPATOLOGY   Vol. 76   page: S1330 - S1330   2022.10

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  23. 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     page: 1 - 10   2022.3

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  24. 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   Vol. 12 ( 1 ) page: 3674   2022.3

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

    Sugiyama Y, Ishizu Y, Ando Y, Yokoyama S, Yamamoto K, Ito T, Imai N, Nakamura M, Honda T, Kawashima H, Ishikawa T, Ishigami M

    European journal of gastroenterology & hepatology   Vol. 33 ( 1S Suppl 1 ) page: e916 - e921   2021.12

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

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  26. Nuclear Receptor CoRepressors, NCOR1 and SMRT, are required for maintaining systemic metabolic homeostasis

    Ritter Megan J., Amano Izuki, Imai Norihiro, De Oliveira Lorraine Soares, Vella Kristen R., Hollenberg Anthony N.

    MOLECULAR METABOLISM   Vol. 53   page: 101315   2021.11

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    Objective: The nuclear receptor corepressor 1 (NCOR1) and the silencing mediator of retinoic acid and thyroid hormone (SMRT, also known as NCOR2) play critical and specific roles in nuclear receptor action. NCOR1, both in vitro and in vivo specifically regulates thyroid hormone (TH) action in the context of individual organs such as the liver, and systemically in the context of the hypothalamic-pituitary-thyroid (HPT) axis. In contrast, selective deletion of SMRT in the liver or globally has shown that it plays very little role in TH signaling. However, both NCOR1 and SMRT have some overlapping roles in hepatic metabolism and lipogenesis. Here, we determine the roles of NCOR1 and SMRT in global physiologic function and find if SMRT could play a compensatory role in the regulation of TH action, globally. Methods: We used a postnatal deletion strategy to disrupt both NCOR1 and SMRT together in all tissues at 8–9 weeks of age in male and female mice. This was performed using a tamoxifen-inducible Cre recombinase (UBC-Cre-ERT2) to KO (knockout) NCOR1, SMRT, or NCOR1 and SMRT together. We used the same strategy to KO HDAC3 in male and female mice of the same age. Metabolic parameters, gene expression, and thyroid function tests were analyzed. Results: Surprisingly, adult mice that acquired NCOR1 and SMRT deletion rapidly became hypoglycemic and hypothermic and perished within ten days of deletion of both corepressors. Postnatal deletion of either NCOR1 or SMRT had no impact on mortality. NCOR1/SMRT KO mice rapidly developed hepatosteatosis and mild elevations in liver function tests. Additionally, alterations in lipogenesis, beta oxidation, along with hepatic triglyceride and glycogen levels suggested defects in hepatic metabolism. The intestinal function was intact in the NCOR1/SMRT knockout (KO) mice. The KO of HDAC3 resulted in a distinct phenotype from the NCOR1/SMRT KO mice, whereas none of the HDAC3 KO mice succumbed after tamoxifen injection. Conclusions: The KO of NCOR1 and SMRT rapidly leads to significant metabolic abnormalities that do not survive – including hypoglycemia, hypothermia, and weight loss. Hepatosteatosis rapidly developed along with alterations in hepatic metabolism suggesting a contribution to the dramatic phenotype from liver injury. Glucose production and absorption were intact in NCOR1/SMRT KO mice, demonstrating a multifactorial process leading to their demise. HDAC3 KO mice have a distinct phenotype from the NCOR1/SMRT KO mice—which implies that NCOR1/SMRT together regulate a critical pathway that is required for survival in adulthood and is separate from HDAC3.

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

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

    ANTICANCER RESEARCH   Vol. 41 ( 11 ) page: 5817 - 5820   2021.11

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    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.

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  28. The absence of large portal collateral vessels is concerned with spontaneous improvement of cirrhotic portal vein thrombosis.

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

    Hepatology research : the official journal of the Japan Society of Hepatology     2021.10

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  29. Immune-related liver injury is a poor prognostic factor in patients with non-small 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     page: 1 - 31   2021.10

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

    Ito Takanori, Ishigami Masatoshi, Yamamoto Takafumi, Mizuno Kazuyuki, Yamamoto Kenta, Imai Norihiro, Ishizu Yoji, Honda Takashi, Kawashima Hiroki, Yasuda Satoshi, Toyoda Hidenori, Yokota Kenji, Hase Tetsunari, Nishio Naoki, Maeda Osamu, Kato Masashi, Hashimoto Naozumi, Hibi Hideharu, Kodera Yasuhiro, Sone Michihiko, Ando Yuichi, Akiyama Masashi, Shimoyama Yoshie, Fujishiro Mitsuhiro

    HEPATOLOGY INTERNATIONAL   Vol. 15 ( 5 ) page: 1278 - 1287   2021.10

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    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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  31. 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   Vol. 74   page: 468A - 469A   2021.10

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  32. The influence of hepatitis C virus eradication on hepatocarcinogenesis in patients with hemophiliaHCC after HCV eradication in 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   Vol. 27 ( 1 ) page: 100545   2021.9

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    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.

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

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

    SCIENTIFIC REPORTS   Vol. 11 ( 1 ) page: 18778   2021.9

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

    Ishigami Masatoshi, Honda Takashi, Ishizu Yoji, Imai Norihiro, Ito Takanori, Yamamoto Kenta, Kamei Hideya, Ogura Yasuhiro, Fujishiro Mitsuhiro

    EXPERIMENTAL AND CLINICAL TRANSPLANTATION   Vol. 19 ( 9 ) page: 935 - 942   2021.9

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    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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  35. Upregulation of Thioesterase Superfamily Member 2 in Skeletal Muscle Promotes Hepatic Steatosis and Insulin Resistance.

    Imai N, Nicholls HT, Alves-Bezerra M, Li Y, Ivanova AA, Ortlund EA, Cohen DE

    Hepatology (Baltimore, Md.)     2021.8

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  36. 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   Vol. 75   page: S787 - S788   2021.7

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  37. Thioesterase superfamily member 1 undergoes stimulus-coupled conformational reorganization to regulate metabolism in mice

    Li Yue, Imai Norihiro, Nicholls Hayley T., Roberts Blaine R., Goyal Samaksh, Krisko Tibor I., Ang Lay-Hong, Tillman Matthew C., Roberts Anne M., Baqai Mahnoor, Ortlund Eric A., Cohen David E., Hagen Susan J.

    NATURE COMMUNICATIONS   Vol. 12 ( 1 ) page: 3493   2021.6

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    In brown adipose tissue, thermogenesis is suppressed by thioesterase superfamily member 1 (Them1), a long chain fatty acyl-CoA thioesterase. Them1 is highly upregulated by cold ambient temperature, where it reduces fatty acid availability and limits thermogenesis. Here, we show that Them1 regulates metabolism by undergoing conformational changes in response to β-adrenergic stimulation that alter Them1 intracellular distribution. Them1 forms metabolically active puncta near lipid droplets and mitochondria. Upon stimulation, Them1 is phosphorylated at the N-terminus, inhibiting puncta formation and activity and resulting in a diffuse intracellular localization. We show by correlative light and electron microscopy that Them1 puncta are biomolecular condensates that are inhibited by phosphorylation. Thus, Them1 forms intracellular biomolecular condensates that limit fatty acid oxidation and suppress thermogenesis. During a period of energy demand, the condensates are disrupted by phosphorylation to allow for maximal thermogenesis. The stimulus-coupled reorganization of Them1 provides fine-tuning of thermogenesis and energy expenditure.

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  38. Prevalence and predictive factors of diabetes in hepatitis virus positive liver cirrhosis with fasting plasma glucose level of <126mg/dL

    MATSUMOTO Naoki, ARASE Yasuji, SEKO Yuya, IMAI Norihiro, KAWAMURA Yusuke, SEZAKI Hitomi, HOSAKA Tetsuya, AKUTA Norio, KOBAYASHI Mariko, KOBAYASHI Masahiro, SUZUKI Yoshiyuki, SAITO Satoshi, SUZUKI Fumitaka, IKEDA Kenji, KUMADA Hiromitsu, AIDA Kaoru, KOBAYASHI Tetsuro

      Vol. 42 ( 6 ) page: 558 - 563   2012.6

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  39. PROLONGED NEW ONSET OF HEPATOCELLULAR CARCINOMA FROM NON-ALCOHOLIC FATTY LIVER DISEASE IN JAPANESE LARGE POPULATION

    Kawamura, Y; Arase, Y; Ikeda, K; Seko, Y; Imai, N; Hosaka, T; Kobayashi, M; Saitoh, S; Sezaki, H; Akuta, N; Suzuki, F; Suzuki, Y; Ohmoto, Y; Amakawa, K; Tsuji, H; Kumada, H

    HEPATOLOGY   Vol. 54   page: 1364A - 1364A   2011.10

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  40. STAGE PROGRESSION OF SMALL HEPATOCELLULAR CARCINOMA AFTER POTENTIALLY RADICAL THERAPY - COMPARISONS OF RADIOFREQUENCY ABLATION AND SURGERY USING MARKOV MODEL

    Ikeda, K; Seko, Y; Imai, N; Hirakawa, M; Kawamura, Y; Sezaki, H; Hosaka, T; Akuta, N; Kobayashi, M; Saitoh, S; Suzuki, F; Suzuki, Y; Arase, Y; Kumada, H

    HEPATOLOGY   Vol. 52 ( 4 ) page: 1184A - 1184A   2010.10

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  41. TUMOR SIZE OF HEPATOCELLULAR CARCINOMA AT DETECTION IS LARGER IN PATIENTS WITH HBV THAN THOSE WITH HCV

    Imai, N; Ikeda, K; Seko, Y; Hirakawa, M; Kawamura, Y; Kobayashi, M; Hosaka, T; Sezaki, H; Akuta, N; Saitoh, S; Suzuki, F; Suzuki, Y; Arose, Y; Kumada, H

    HEPATOLOGY   Vol. 52 ( 4 ) page: 1180A - 1180A   2010.10

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

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

    Internal medicine (Tokyo, Japan)   Vol. 63 ( 1 ) page: 57 - 61   2024

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

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  43. Endoscopic injection sclerotherapy with polidocanol for cardiac varices in children and adolescents. International journal

    Shinya Yokoyama, Yoji Ishizu, Takashi Honda, Norihiro Imai, Takanori Ito, Kenta Yamamoto, Akinari Hinoki, Wataru Sumida, Chiyoe Shirota, Takahisa Tainaka, Satoshi Makita, Kazuki Yokota, Hiroo Uchida, Masatoshi Ishigami

    Archives de pediatrie : organe officiel de la Societe francaise de pediatrie   Vol. 30 ( 2 ) page: 109 - 112   2023.2

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

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  44. Decreased appetite is associated with the presence of sarcopenia in patients with cirrhosis. International journal

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

    Nutrition (Burbank, Los Angeles County, Calif.)   Vol. 103   page: 111807 - 111807   2022.11

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

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  45. Factors associated with the progression of myosteatosis in patients with cirrhosis. International journal

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

    Nutrition (Burbank, Los Angeles County, Calif.)   Vol. 103   page: 111777 - 111777   2022.11

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    OBJECTIVES: The presence of myosteatosis is one factor associated with poor prognosis for patients with cirrhosis; however, the factors contributing to worsening myosteatosis are, to our knowledge, unknown. The aim of this study was to clarify the changes in myosteatosis, and the factors involved in these changes. METHODS: The present study enrolled 178 patients with cirrhosis who underwent computed tomography twice to measure changes in skeletal muscle attenuation (SMA) at the L3 level. Factors associated with SMA and those associated with changes in SMA were examined. RESULTS: Using linear multiple regression analysis, age (β = -0.22), skeletal muscle index (SMI; skeletal muscle area divided by height squared; β = 0.25), and visceral and subcutaneous fat indices (VFI and SFI; the visceral and subcutaneous fat areas at the umbilical level divided by height squared; β = -0.08, β = -0.06, respectively) were identified as associated with SMA. The 100-d change in SMA was -0.21 ± 1.29 Hounsfield units (HU). Changes in SMI and SMA were positively associated (R = 0.183, P = 0.014), whereas those in VFI and SMA were negatively associated (R = -0.172, P = 0.022). No association was noted between the 100-d changes in SFI and SMA. In patients whose SMI increased and VFI decreased, the 100-d change in SMA was 0.24 ± 1.82 HU, which was marginally different from that in patients whose SMI decreased and VFI increased (-0.44 ± 1.32 HU, P = 0.077). CONCLUSIONS: In patients with cirrhosis, myosteatosis progressed, and decreases in SMI and increases in VFI were correlated with its progression.

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

    Norihiro Imai, Masatoshi Ishigami, Yumi Oie, Motoki Kumagai, Yosuke Inukai, Shinya Yokoyama, Kenta Yamamoto, Takanori Ito, Yoji Ishizu, Takashi Honda, Hiroki Kawashima

    Anticancer research   Vol. 42 ( 8 ) page: 3947 - 3951   2022.8

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

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  47. A case of antiprogrammed death-ligand 1 antibody-induced multisystem immune-related adverse events with pancreatitis and steroid-resistant sclerosing cholangitis. International journal

    Takafumi Yamamoto, Takanori Ito, Kazuyuki Mizuno, Yokoyama Shinya, Kenta Yamamoto, Norihiro Imai, Yoji Ishizu, Takashi Honda, Hiroki Kawashima, Toshinori Matsui, Tetsunari Hase, Naozumi Hashimoto, Masatoshi Ishigami

    Journal of digestive diseases   Vol. 23 ( 7 ) page: 404 - 409   2022.7

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  48. Tolerability of Molecular-targeted Agents for Hepatocellular Carcinoma Treatment in Haemophiliacs.

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

    Anticancer research   Vol. 41 ( 5 ) page: 2569 - 2573   2021.5

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

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

    CLINICAL NUTRITION ESPEN   Vol. 42   page: 354 - 360   2021.4

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  50. Progression After Molecular Targeted Agents: Hepatic Arterial Changes and Transarterial Chemoembolization in Hepatocellular Carcinoma.

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

    In vivo (Athens, Greece)   Vol. 35 ( 2 ) page: 1185 - 1189   2021.3

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

    Yamamoto Takafumi, Imai Norihiro, Yamamoto Kenta, Ito Takanori, Ishizu Yoji, Honda Takashi, Okamoto Shuichi, Kanematsu Takeshi, Suzuki Nobuaki, Matsushita Tadashi, Ishigami Masatoshi, Fujishiro Mitsuhiro

    HAEMOPHILIA   Vol. 27 ( 1 ) page: 100 - 107   2021.1

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

    Ito Takanori, Ishigami Masatoshi, Morooka Hikaru, Yamamoto Kenta, Imai Norihiro, Ishizu Yoji, Honda Takashi, Nishimura Daisaku, Tada Toshifumi, Yasuda Satoshi, Toyoda Hidenori, Kumada Takashi, Fujishiro Mitsuhiro

    SCIENTIFIC REPORTS   Vol. 10 ( 1 ) page: 17812   2020.10

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  53. Allosteric regulation of thioesterase superfamily member 1 by lipid sensor domain binding fatty acids and lysophosphatidylcholine

    Tillman Matthew C., Imai Norihiro, Li Yue, Khadka Manoj, Okafor C. Denise, Juneja Puneet, Adhiyaman Akshitha, Hagen Susan J., Cohen David E., Ortlund Eric A.

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   Vol. 117 ( 36 ) page: 22080 - 22089   2020.9

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  54. Them1 Binds to Free Fatty Acids and is Allosterically Regulated by Lysophosphatidylcholine to Control Fatty Acyl-CoA Hydrolysis in Brown Adipose Tissue

    Tillman Matthew, Li Yue, Khadka Manoj, Imai Norihiro, Adhiyaman Akshitha, Juneja Puneet, Hagen Susan, Cohen David, Ortlund Eric

    FASEB JOURNAL   Vol. 34   2020.4

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  55. Thioesterase Superfamily Member 1 Undergoes Stimulus-coupled Reorganization to Regulate Metabolic Activity in Brown Adipose Tissue

    Li Yue, Imai Norihiro, Goyal Samaksh, Nicholls Hayley, Krisko Tibor, Baqai Mahnoor, Ang Lay-Hong, Tillman Matthew, Ortlund Eric, Cohen David, Hagen Susan

    FASEB JOURNAL   Vol. 34   2020.4

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  56. Hepatology Highlights.

    Shah PA, Lau DTY, Russo NW, Brown RS Jr, Maiers JL, Schwartz RE, Imai N, Krisko TI, Navarro-Corcuera A, Jalan-Sakrikar N, Pisa JF, Jesudian AB, Tafesh ZH, Fortune BE, Kostallari E

    Hepatology (Baltimore, Md.)   Vol. 71 ( 1 ) page: 1 - 3   2020.1

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  57. Trimming the Fat: Acetyl-CoA Carboxylase Inhibition for the Management of NAFLD.

    Imai N, Cohen DE

    Hepatology (Baltimore, Md.)   Vol. 68 ( 6 ) page: 2062 - 2065   2018.12

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  58. Hepatocyte-specific depletion of ubiquitin regulatory X domain containing protein 8 accelerates fibrosis in a mouse non-alcoholic steatohepatitis model

    Imai Norihiro, Suzuki Michitaka, Ishizu Yoji, Kuzuya Teiji, Honda Takashi, Hayashi Kazuhiko, Ishigami Masatoshi, Hirooka Yoshiki, Ishikawa Tetsuya, Goto Hidemi, Fujimoto Toyoshi

    HISTOCHEMISTRY AND CELL BIOLOGY   Vol. 148 ( 3 ) page: 219 - 227   2017.9

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  59. Hepatocyte-Specific Depletion of UBXD8 Induces Periportal Steatosis in Mice Fed a High-Fat Diet

    Imai Norihiro, Suzuki Michitaka, Hayashi Kazuhiko, Ishigami Masatoshi, Hirooka Yoshiki, Abe Takaya, Shioi Go, Goto Hidemi, Fujimoto Toyoshi

    PLOS ONE   Vol. 10 ( 5 ) page: e0127114   2015.5

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  60. Transarterial chemoembolization for hepatocellular carcinoma: A review of techniques.

    Imai N, Ishigami M, Ishizu Y, Kuzuya T, Honda T, Hayashi K, Hirooka Y, Goto H

    World journal of hepatology   Vol. 6 ( 12 ) page: 844 - 50   2014.12

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  61. 当院におけるHBV感染と肝発癌の検討

    荒川 恭宏, 加藤 幸一郎, 新家 卓郎, 今井 則博, 阿知波 宏一, 山田 恵一, 石津 洋二, 葛谷 貞二, 本多 隆, 林 和彦, 石上 雅敏, 後藤 秀実

    肝臓   Vol. 55 ( Suppl.2 ) page: A599 - A599   2014.9

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  62. The relationship between the fever and the disappearance or decrease of lesion contrast on contrast enhanced CT images after 2 weeks of sorafenib treatment for patients with advanced hepatocellular carcinoma

    KUZUYA Teiji, ISHIGAMI Masatoshi, NIINOMI Takurou, IMAI Norihiro, ACHIWA Kouichi, ARAKAWA Takahiro, YAMADA Keiichi, NAKANO Satoshi, ISHIZU Yoji, HONDA Takashi, HAYASHI Kazuhiko, ISHIKAWA Tetsuya, NAKANO Isao, KATANO Yoshiaki, ITOH Akihiro, HIROOKA Yoshiki, GOTO Hidemi

    Kanzo   Vol. 54 ( 7 ) page: 505 - 506   2013.5

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    We investigated the relationship between the fever and the disappearance or decrease of lesion contrast on contrast enhanced CT images after 2 weeks of sorafenib treatment for patients with advanced hepatocellular carcinoma (HCC). Subjects were 64 patients who began sorafenib therapy. Contrast enhanced CT images were taken at baseline and after 2 weeks of sorafenib treatment. In patients with fever, the ratio of patients demonstrating the disappearance or decrease of lesion contrast on contrast enhanced CT images was significantly higher than in those without fever (91.3% and 61.0%, respectively, p=0.010, Fisher's exact probability test). The results suggested the relationship between the fever and contrast change on contrast enhanced CT.<br>

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  63. Transcatheter arterial chemotherapy with miriplatin for hepatocellular carcinoma patients with chronic renal failure: report of three cases.

    Imai N, Ikeda K, Seko Y, Kawamura Y, Sezaki H, Hosaka T, Akuta N, Kobayashi M, Saitoh S, Suzuki F, Suzuki Y, Arase Y, Kumada H

    Gut and liver   Vol. 7 ( 2 ) page: 246 - 51   2013.3

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  64. Clinical trial of percutaneous radio frequency ablation therapy by two-step insertion method using VirtuTRAX<sup>TM</sup> instrument navigator

    Kuzuya Teiji, Hayashi Kazuhiko, Ishigami Masatoshi, Ishikawa Tetsuya, Nakano Isao, Katano Yoshiaki, Itoh Akihiro, Hirooka Yoshiki, Izumi Namiki, Goto Hidemi, Ishizu Yoji, Niinomi Takurou, Imai Norihiro, Achiwa Kouichi, Arakawa Takahiro, Yamada Keiichi, Nakano Satoshi, Honda Takashi

    Kanzo   Vol. 54 ( 12 ) page: 850 - 853   2013

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    We performed percutaneous radio frequency ablation (RFA) therapy by two-step insertion method using VirtuTRAX<sup>TM</sup> (GE Healthcare, USA) instrument navigator. Subjects were 16 patients (23 nodules) with hepatocellular carcinoma. VirtuTRAX<sup>TM</sup> position sensor was attached to the hilt of 14-gauge outer needle. In all cases, we could perform 17- gauge Cool-tip RFA without the positional gap between the virtual tract and the actual needle which was caused by the deflection of the needle. The reasons without causing the positional gap were that the outer needle was more rigid than Cool-tip needle, and that it was inserted using initial insertion of a 21-gauge guided needle. RFA by two-step insertion method using VirtuTRAX<sup>TM</sup> is suggested to be more safe and effective than conventional RFA.

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  65. An Increase in Lesion Density can Predict Lower Local Recurrence after Transarterial Chemoembolization in Patients with Hepatocellular Carcinoma

    Imai Norihiro, Katano Yoshiaki, Kuzuya Teiji, Honda Takashi, Hayashi Kazuhiko, Ishigami Masatoshi, Itoh Akihiro, Hirooka Yoshiki, Goto Hidemi

    HEPATO-GASTROENTEROLOGY   Vol. 60 ( 125 ) page: 965 - 970   2013

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  66. Efficacy of reduction therapy of natural human β-interferon and ribavirin in elderly patients with chronic hepatitis C, genotype 2 and high virus load

    ARASE Yasuji, SUZUKI Yoshiyuki, SUZUKI Fumitaka, AKUTA Norio, SEZAKI Hitomi, KAWAMURA Yusuke, KOBAYASHI Masahiro, IMAI Norihiro, SEKO Yuya, HOSAKA Tetsuya, MATSUMOTO Naoki, SAITO Satoshi, IKEDA Kenji, KOBAYASHI Mariko, KUMADA Hiromitsu

    Hepatology research : the official journal of the Japan Society of Hepatology   Vol. 42 ( 8 ) page: 750 - 756   2012.8

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  67. Combination therapy with transcatheter arterial infusion chemotherapy using miriplatin and percutaneous radiofrequency ablation for hepatocellular carcinoma

    IMAI Norihiro, IKEDA Kenji, SEKO Yuya, HARA Tasuku, OHNO Atsushi, MATSUMOTO Naoki, KAWAMURA Yusuke, HOSAKA Tetsuya, KOBAYASHI Masahiro, SAITOH Satoshi, SEZAKI Hitomi, AKUTA Norio, SUZUKI Fumitaka, SUZUKI Yoshiyuki, ARASE Yasuji, KUMADA Hiromitsu

    Kanzo   Vol. 53 ( 6 ) page: 351-354 - 354   2012.6

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    Miriplatin is a platinum complex developed to treat hepatocellular carcinoma (HCC) via administration into the hepatic artery as a sustained-release suspension in iodized oil. We retrospectively evaluated the efficacy of combination therapy with transcatheter arterial infusion chemotherapy using miriplatin and percutaneous radiofrequency ablation for HCC in 11 patients. Immediately after transcatheter arterial infusion chemotherapy using miriplatin, we performed radiofrequency ablation. The greatest long-axis and short-axis dimensions of the area coagulated after combination therapy were 42 mm (35-80 mm) and 34 mm (32-60 mm), respectively. During follow-up (median 12 months), there was no recurrence from the same subsegment. No serious adverse events were observed. These results suggested that using the combination therapy, it is possible to finish one treatment session for patient with HCC.<br>

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  68. Prevalence and predictive factors of diabetes in hepatitis virus positive liver cirrhosis with fasting plasma glucose level of &lt;126 mg/dL

    Matsumoto, N; Arase, Y; Seko, Y; Imai, N; Kawamura, Y; Sezaki, H; Hosaka, T; Akuta, N; Kobayashi, M; Kobayashi, M; Suzuki, Y; Saito, S; Suzuki, F; Ikeda, K; Kumada, H; Aida, K; Kobayashi, T

    HEPATOLOGY RESEARCH   Vol. 42 ( 6 ) page: 558 - 563   2012.6

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    Aim: The aim of this study was to evaluate the prevalence and predictive factors of diabetes in hepatitis virus positive liver cirrhotic patients with fasting plasma glucose (FPG) level of <126mg/dL. Methods: A total of 263 patients with hepatitis C virus (HCV) or hepatitis B virus (HBV) positive liver cirrhosis, FPG level of <126mg/dL, and had diabetes status evaluated by the use of 75-g oral glucose tolerance test (OGTT), were enrolled in this study. Plasma glucose and insulin levels were analyzed periodically for 3h after oral glucose loading. Diabetes was defined as a 2-h post-load glucose on the OGTT of ≥200mg/dL. The prevalence of diabetes by use of OGTT and predictive factors for diabetes were evaluated by the use of the Mann-Whitney U-test, Fisher's exact probability test or multivariate analysis by logistic regression. Hypoalbuminemia was defined as serum albumin level of <3.9g/dL. Elevated indocyanine green retention rate at 15min (ICG R15) was regarded as ≥ 25%. Results: Out of 263 patients, 44 (16.7%) were diagnosed as having diabetes. Multivariate analysis showed that diabetes occurred when patients had hypoalbuminemia of <3.9g/dL (odds ratio [OR] 2.33; 95% confidential interval [CI]=1.04-5.24; P=0.040) and ICG R15 of <25% (OR 2.36; 95%CI=1.01-5.58). Conclusions: Hypoalbuminemia and elevated ICG R15 in hepatitis virus related cirrhotic patients with FPG level of <126mg/day enhance diabetes pattern after OGTT with significant difference. © 2012 The Japan Society of Hepatology.

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  69. Difference in malignancies of chronic liver disease due to non-alcoholic fatty liver disease or hepatitis C in Japanese elderlv patients

    ARASE Yasuji, KOBAYASHI Mariko, SUZUKI Fumitaka, SUZUKI Yoshiyuki, KAWAMURA Yusuke, AKUTA Norio, IMAI Norihiro, KOBAYASHI Masahiro, SEZAKI Hitomi, MATSUMOTO Naoki, SAITO Satoshi, HOSAKA Tetsuya, IKEDA Kenji, KUMADA Hiromitsu, OHMOTO Yuki, AMAKAWA Kazuhisa, HSIEH Shiun Dong, OGAWA Kyoko, TANABE Maho, TSUJI Hiroshi, KOBAYASHI Tetsuro

    Hepatology research : the official journal of the Japan Society of Hepatology   Vol. 42 ( 3 ) page: 264 - 272   2012.3

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  70. Transcatheter arterial chemotherapy using miriplatin-lipiodol suspension with or without embolization for unresectable hepatocellular carcinoma.

    Imai N, Ikeda K, Kawamura Y, Sezaki H, Hosaka T, Akuta N, Kobayashi M, Saitoh S, Suzuki F, Suzuki Y, Arase Y, Kumada H

    Japanese journal of clinical oncology   Vol. 42 ( 3 ) page: 175 - 82   2012.3

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  71. Difference in malignancies of chronic liver disease due to non-alcoholic fatty liver disease or hepatitis C in Japanese elderly patients.

    Arase Y, Kobayashi M, Suzuki F, Suzuki Y, Kawamura Y, Akuta N, Imai N, Kobayashi M, Sezaki H, Matsumoto N, Saito S, Hosaka T, Ikeda K, Kumada H, Ohmoto Y, Amakawa K, Hsieh SD, Ogawa K, Tanabe M, Tsuji H, Kobayashi T

    Hepatology research : the official journal of the Japan Society of Hepatology   Vol. 42 ( 3 ) page: 264 - 272   2012.3

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  72. Large-scale long-term follow-up study of Japanese patients with non-alcoholic Fatty liver disease for the onset of hepatocellular carcinoma.

    Kawamura Y, Arase Y, Ikeda K, Seko Y, Imai N, Hosaka T, Kobayashi M, Saitoh S, Sezaki H, Akuta N, Suzuki F, Suzuki Y, Ohmoto Y, Amakawa K, Tsuji H, Kumada H

    The American journal of gastroenterology   Vol. 107 ( 2 ) page: 253 - 61   2012.2

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  73. Transcatheter arterial chemotherapy with miriplatin for patients with hepatocellular carcinoma and chronic renal failure

    IMAI Norihiro, IKEDA Kenji, SEKO Yuya, MATSUMOTO Naoki, KAWAMURA Yusuke, HOSAKA Tetsuya, KOBAYASHI Masahiro, SAITOH Satoshi, SEZAKI Hitomi, AKUTA Norio, SUZUKI Fumitaka, SUZUKI Yoshiyuki, ARASE Yasuji, KUMADA Hiromitsu

    Nippon Shokakibyo Gakkai Zasshi   Vol. 108 ( 11 ) page: 1872-1878 - 1878   2011.11

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    Miriplatin is a novel lipophilic platinum complex developed to treat hepatocellular carcinoma (HCC). Although HCC patients frequently have coexisting chronic renal failure, there is no reliable data regarding clinical toxicity of miriplatin in HCC patients with chronic renal failure. We retrospectively evaluated the safety and efficacy of transcatheter arterial chemotherapy with miriplatin in 67 HCC patients with chronic renal failure (estimated glomerular filtration rate [GFR] by the Cockcroft-Gault equation <60m<i>l</i>/min). Estimated GFR within 2 months after miriplatin administration did not decrease significantly by the Wilcoxon signed rank test (pretreatment;46m<i>l</i>/min, 1 month;48m<i>l</i>/min;<i>P</i>=0.019, 2 months;45m<i>l</i>/min;<i>P</i>=0.619 [<i>P</i><0.003 was significant by the Bonferroni correction]). Complete response in terms of tumor necrosis was achieved in 14 of 67 patients and no serious adverse events were observed. These results suggested that transcatheter arterial chemotherapy with miriplatin can be used safely for HCC patients with chronic renal failure.<br>

    DOI: 10.11405/nisshoshi.108.1872

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  74. Transcatheter arterial chemotherapy with miriplatin for patients with hepatocellular carcinoma and chronic renal failure

    Imai N.

    Journal of Japanese Society of Gastroenterology   Vol. 108 ( 11 ) page: 1872-1878   2011.11

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  75. Development rate of chronic kidney disease in hepatitis C virus patients with advanced fibrosis after interferon therapy

    ARASE Yasuji, SUZUKI Fumitaka, KAWAMURA Yusuke, SUZUKI Yoshiyuki, KOBAYASHI Masahiro, MATSUMOTO Naoki, AKUTA Norio, SEZAKI Hitomi, HOSAKA Tetsuya, OGAWA Kyoko, IMAI Norihiro, SEKO Yuya, SAITO Satoshi, IKEDA Kenji, KOBAYASHI Mariko, KUMADA Hiromitsu

    Hepatology research : the official journal of the Japan Society of Hepatology   Vol. 41 ( 10 ) page: 946 - 954   2011.10

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  76. A case of intractable hepatic encephalopathy successfully treated by oral administration of vancomycin hydrochloride, with subsequent improvement of hepatic function reserve enabling transcatheter arterial chemoembolization against hepatocellular carcinoma

    Kuzuya T.

    Japanese Journal of Cancer and Chemotherapy   Vol. 38 ( 6 ) page: 995 - 997   2011.6

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  77. Clearance of hepatitis B surface antigen during long-term nucleot(s)ide analogues treatment in chronic hepatitis B

    HOSAKA Tetsuya, SUZUKI Fumitaka, KOBAYASHI Masahiro, SEKO Yuya, IMAI Norihiro, HIRAKAWA Miharu, KAWAMURA Yusuke, SEZAKI Hitomi, AKUTA Norio, SUZUKI Yoshiyuki, SAITOH Satoshi, ARASE Yasuji, IKEDA Kenji, KOBAYASHI Mariko, KUMADA Hiromitsu

    Kanzo   Vol. 52 ( 4 ) page: 255 - 257   2011.6

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    Clearance of HBsAg is considered the ultimate goal in the treatment for chronic hepatitis B. We analyzed clinical factors associated with HBsAg clearance during long-term nucleot(s)ide analogue treatment. By univariate analysis, HBV genotype, family history of HBV infection, previous IFN therapy, HBeAg clearance at 6 months, and undetectable HBV DNA at 6 months were significant predictive factors. By multivariate analysis, HBV genotype, previous IFN therapy, HBeAg clearance at 6 months, and undetectable HBV DNA at 6 months were independent and significant predictive factors of HBsAg clearance. We conclude that patients with genotype A have high probability of HBsAg clearance, and it seems that not only the antiviral potential of nucleot(s)ide analogue but host immune response is needed to achieve HBsAg clearance.<br>

    DOI: 10.2957/kanzo.52.255

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  78. Efficacy and safety in sitagliptin therapy for diabetes complicated by chronic liver disease caused by hepatitis C virus

    Arase Y

    Hepatology Research   Vol. 41 ( 6 ) page: 524 - 529   2011.6

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    DOI: 10.1111/j.1872-034X.2011.00798.x

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  79. Stage progression of small hepatocellular carcinoma after radical therapy: comparisons of radiofrequency ablation and surgery using the Markov model.

    Ikeda K, Kobayashi M, Kawamura Y, Imai N, Seko Y, Hirakawa M, Hosaka T, Sezaki H, Akuta N, Saitoh S, Suzuki F, Suzuki Y, Arase Y, Kumada H

    Liver international : official journal of the International Association for the Study of the Liver   Vol. 31 ( 5 ) page: 692 - 9   2011.5

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    DOI: 10.1111/j.1478-3231.2011.02480.x

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  80. Effect of early antiviral agent therapy (NS3 and NS5A inhibitors) in chronic hepatitis C null responders

    SUZUKI Yoshiyuki, SEZAKI Hitomi, AKUTA Norio, SUZUKI Fumitaka, SEKO Hiroya, IMAI Norihiro, HIRAKAWA Miharu, KAWAMURA Yuusuke, HOSAKA Tetsuya, KOBAYASHI Masahiro, SAITOH Satoshi, ARASE Yasuji, IKEDA Kenji, KOBAYASHI Mariko, KUMADA Hiromitsu

    Kanzo   Vol. 52 ( 2 ) page: 147 - 149   2011.4

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    To further improve therapeutic effect on chronic hepatitis C, we have administered NS3 inhibitor and NS5A inhibitor together, and examined effects of early antiviral agent therapy. The subjects were five cases where interferon is ineffective (null responders). The NS5A and NS3 inhibitors are oral drugs and were daily administered for 24 weeks. Figure 1 shows time-dependent change of the number of viruses after the therapy started, and rapid decrease of viruses is recognized. Within 12 hours, HCV-RNA decreased by more than 2 log IU/m<i>l</i> in every patient. Two patients became negative for the virus by the 15th day after the therapy started. Furthermore, 80% of cases by the 28th day and all the cases by the 56th day became negative. The new therapy has manifested excellent early antiviral effect.<br>

    DOI: 10.2957/kanzo.52.147

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  81. Efficacy and safety of combination therapy of natural human interferon beta and ribavirin in chronic hepatitis C patients.

    Arase Y, Suzuki Y, Suzuki F, Matsumoto N, Akuta N, Imai N, Seko Y, Sezaki H, Kawamura Y, Kobayashi M, Hosaka T, Saito S, Ikeda K, Kobayashi M, Kumada H

    Internal medicine (Tokyo, Japan)   Vol. 50 ( 19 ) page: 2083 - 8   2011

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    DOI: 10.2169/internalmedicine.50.5767

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  82. Previous chemoembolization response after transcatheter arterial chemoembolization (TACE) can predict the anti-tumor effect of subsequent TACE with miriplatin in patients with recurrent hepatocellular carcinoma.

    Imai N, Ikeda K, Seko Y, Kawamura Y, Sezaki H, Hosaka T, Akuta N, Kobayashi M, Saitoh S, Suzuki F, Suzuki Y, Arase Y, Kumada H

    Oncology   Vol. 80 ( 3-4 ) page: 188 - 94   2011

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    DOI: 10.1159/000328749

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  83. Administration of interferon for two or more years decreases early stage hepatocellular carcinoma recurrence rate after radical ablation : A retrospective study of hepatitis C virus-related liver cancer

    IKEDA Kenji, KOBAYASHI Masahiro, SEKO Yuya, IMAI Norihiro, HIRAKAWA Miharu, KAWAMURA Yusuke, SEZAKI Hitomi, HOSAKA Tetsuya, AKUTA Norio, SAITOH Satoshi, SUZUKI Fumitaka, SUZUKI Yoshiyuki, ARASE Yasuji, KUMADA Hiromitsu

    Hepatology research : the official journal of the Japan Society of Hepatology   Vol. 40 ( 12 ) page: 1168-1175   2010.12

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  84. Transcatheter arterial chemotherapy with miriplatin for patients with hepatocellular carcinoma and Child-Pugh B liver cirrhosis

    IMAI Norihiro, IKEDA Kenji, SEKO Yuya, HIRAKAWA Miharu, KAWAMURA Yusuke, HOSAKA Tetsuya, KOBAYASHI Masahiro, SAITOH Satoshi, SEZAKI Hitomi, AKUTA Norio, SUZUKI Fumitaka, SUZUKI Yoshiyuki, ARASE Yasuji, KUMADA Hiromitsu

    Kanzo   Vol. 51 ( 12 ) page: 758 - 760   2010.12

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    Miriplatin is a novel lipophilic platinum complex developed to treat hepatocellular carcinoma (HCC). Although HCC patients frequently have coexisting severe liver cirrhosis, there is no prospective data regarding clinical toxicity of miriplatin in HCC patients with severe cirrhosis. We retrospectively evaluated the safety and efficacy of transcatheter arterial chemotherapy with miriplatin in 34 HCC patients with severe liver cirrhosis (Child-Pugh grade B). An anti-tumor effect of complete response was achieved in 8 of 34 patients and no serious adverse events were observed. These results suggested that transcatheter arterial chemotherapy with miriplatin can be used safety for HCC patients with Child-Pugh B liver cirrhosis.<br>

    DOI: 10.2957/kanzo.51.758

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  85. A case of metastatic pancreatic cancer with a remarkable response to combination therapy of gemcitabine and adoptive immune cell therapy

    Imai N.

    Japanese Journal of Cancer and Chemotherapy   Vol. 37 ( 3 ) page: 527 - 529   2010.3

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  86. High Incidence of Colonic Perforation During Colonoscopy in Hemodialysis Patients With End-Stage Renal Disease

    Imai Norihiro, Takeda Kinichi, Kuzuya Teiji, Utsunomiya Setsuo, Takahashi Hiroshi, Kasuga Hirotake, Asai Masami, Yamada Michiko, Tanikawa Yutaka, Goto Hidemi

    CLINICAL GASTROENTEROLOGY AND HEPATOLOGY   Vol. 8 ( 1 ) page: 55 - 59   2010.1

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    Publishing type:Research paper (scientific journal)   Publisher:Clinical Gastroenterology and Hepatology  

    DOI: 10.1016/j.cgh.2009.09.029

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  87. A case of hepatitis b-related multiple hepatocellular carcinomas, most of which lead to necrosis possibly due to the implantation of an arterial infusion catheter

    Kuzuya T.

    Japanese Journal of Cancer and Chemotherapy   Vol. 36 ( 12 ) page: 2377 - 2379   2009.11

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Books 3

  1. Japanese Cost Management Based on Respect for the Humanity of Employees: The Case of Toyota

    Imai N.( Role: Sole author)

    Japanese Management and International Studies - Vol. 20: Sustainability Management and Network Management  2023.1  ( ISBN:9789811272257

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    DOI: 10.1142/9789811272264_0006

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  2. 肝癌診療ハンドブック ケースで学ぶ集学的治療のコツとセンス

    今井則博, 池田健次( Role: Joint author ,  ケースカンファレンス, 肝癌スクリーニングフローチャート, 各種モダリティの長所と短所, EOB-MRI肝細胞相でのみ低信号結節として指摘できる病変の診断, 肝動脈化学塞栓療法(TACE) 他)

    南江堂  2012 

  3. 劇症肝炎, 病気がみえる vol. 1 消化器 第4版

    今井則博, 荒瀬康司( Role: Joint author ,  劇症肝炎)

    メディックメディア  2010 

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MISC 7

  1. Intermediate stageの進行肝細胞癌に対するソラフェニブの治療成績

    葛谷 貞二, 石上 雅敏, 安藤 祐資, 伊藤 隆徳, 安田 諭, 川口 彩, 加藤 幸一郎, 新家 卓郎, 今井 則博, 石津 洋二, 本多 隆, 林 和彦, 後藤 秀実

    日本消化器病学会雑誌   Vol. 113 ( 臨増総会 ) page: A352 - A352   2016.3

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  2. 当院における肝細胞癌に対するマイクロバルーン閉塞下肝動脈化学塞栓療法(B-TACE)とConventional-TACEとの治療成績の比較

    新家 卓郎, 葛谷 貞二, 安田 諭, 川口 彩, 加藤 幸一郎, 今井 則博, 阿知波 宏一, 山田 恵一, 石津 洋二, 本多 隆, 林 和彦, 石上 雅敏, 後藤 秀実

    肝臓   Vol. 56 ( Suppl.1 ) page: A528 - A528   2015.4

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  3. CA19-9高値で見つかった進行肝細胞癌に対しソラフェニブが奏功した一例

    安田諭, 葛谷貞二, 安藤祐資, 伊藤隆徳, 川口彩, 加藤幸一郎, 新家卓郎, 今井則博, 阿知波宏一, 石津洋二, 本多隆, 林和彦, 石上雅敏, 廣岡芳樹, 石川哲也, 後藤秀実

    肝臓   Vol. 56 ( Supplement 3 ) page: A1051 - A1051   2015

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  4. 高齢者C型慢性肝炎におけるDaclatasvir/Asunaprevir併用療法の早期反応と治療効果

    本多隆, 石上雅敏, 安藤祐資, 安田諭, 伊藤隆徳, 川口彩, 加藤幸一郎, 新家卓郎, 今井則博, 阿知波宏一, 石津洋二, 葛谷貞二, 林和彦, 石川哲也, 中野功, 後藤秀実

    肝臓   Vol. 56 ( Supplement 3 ) page: A1046 - A1046   2015

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  5. 進行肝細胞癌に対するソラフェニブ不応後TACEを組み合わせた症例の治療成績

    葛谷貞二, 石上雅敏, 伊藤隆徳, 安田諭, 川口彩, 加藤幸一郎, 新家卓郎, 今井則博, 阿知波宏一, 石津洋二, 本多隆, 林和彦, 石川哲也, 後藤秀実

    日本消化器病学会大会(Web)   Vol. 57th ( 臨増大会 ) page: A871 - A871   2015

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  6. 治療困難症例におけるV-Naviを駆使した確実かつ安全なRFA治療の工夫 バブルが生じた後の針先端位置調節におけるVirtuTRAXの有用性に着目して

    葛谷 貞二, 新家 卓郎, 加藤 幸一郎, 今井 則博, 阿知波 宏一, 荒川 恭宏, 山田 恵一, 石津 洋二, 本多 隆, 林 和彦, 石上 雅敏, 後藤 秀実

    肝臓   Vol. 55 ( Suppl.1 ) page: A308 - A308   2014.4

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  7. コリン欠乏と閉経及びRaloxifeneによるNASH進展への影響

    LUO F., 加藤幸一郎, 新家卓郎, 今井則博, 阿知波宏一, 荒川恭宏, 山田恵一, 石津洋二, 葛谷貞二, 本多隆, 林和彦, 石上雅敏, 石川哲也, 後藤秀実

    肝臓   Vol. 55 ( Supplement 2 ) page: A623 - A623   2014

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Presentations 16

  1. SUPPRESSION OF FATTY ACID OXIDATION BY THIOESTERASE SUPERFAMILY MEMBER 2 IN SKELETAL MUSCLE PROMOTES HEPATIC STEATOSIS AND INSULIN RESISTANCE

    Imai Norihiro, Alves-Bezerra Michele, Li Yingxia, Cohen David E.

    HEPATOLOGY 

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    Event date: 2019.10

    Language:English   Presentation type:Oral presentation (general)  

  2. Muscle-Specific Metabolic Regulation By Thioesterase Superfamily Member 2 in the Pathogenesis of Nonalcoholic Fatty Liver Disease

    Imai Norihiro, Cohen David E.

    HEPATOLOGY 

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    Event date: 2018.10

    Language:English   Presentation type:Oral presentation (general)  

  3. Hepatocyte-Specific Depletion of Ubiquitin Regulatory X Domain-Containing 8 (UBXD8) Induces Marked Fibrosis in Mice Fed a Short-Term Non-Alcoholic Steatohepatitis (NASH) Model Diet

    Imai Norihiro, Ishizu Yoji, Kuzuya Teiji, Honda Takashi, Hayashi Kazuhiko, Ishigami Masatoshi, Hirooka Yoshiki, Fujimoto Toyoshi, Goto Hidemi

    HEPATOLOGY 

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    Event date: 2016.10

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  4. Hepatocyte-specific depletion of UBXD8 accelerates fibrosis in a mouse non-alcoholic steatohepatitis model

    Imai Norihiro, Ishizu Yoji, Kuzuya Teiji, Honda Takashi, Hayashi Kazuhiko, Ishigami Masatoshi, Hirooka Yoshiki, Fujimoto Toyoshi, Goto Hidemi

    HEPATOLOGY 

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    Event date: 2015.10

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  5. Hepatocyte-specific deletion of UBXD8 induces periportal steatosis after high-fat diet feeding

    Imai Norihiro, Suzuki Michitaka, Ishizu Yoji, Kuzuya Teiji, Honda Takashi, Hayashi Kazuhiko, Ishigami Masatoshi, Fujimoto Toyoshi, Goto Hidemi

    HEPATOLOGY 

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    Event date: 2014

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  6. Trimming the Fat: Acetyl-CoA Carboxylase Inhibition for the Management of NAFLD

    Imai Norihiro, Cohen David E

    HEPATOLOGY  2018.12  Hepatology

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  7. Thioesterase Superfamily Member 1 Undergoes Stimulus-coupled Reorganization to Regulate Metabolic Activity in Brown Adipose Tissue

    Li Yue, Imai Norihiro, Goyal Samaksh, Nicholls Hayley, Krisko Tibor, Baqai Mahnoor, Ang Lay-Hong, Tillman Matthew, Ortlund Eric, Cohen David, Hagen Susan

    FASEB JOURNAL  2020.4 

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  8. 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  2020.11 

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  9. 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  2020.11 

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  10. MODELING NAFLD IN HIGH FAT FED MICE: IDENTIFICATION OF A THRESHOLD VALUE FOR HEPATIC STEATOSIS AND METABOLIC DYSFUNCTION

    Imai Norihiro, Cohen David E

    HEPATOLOGY  2020.11 

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  11. 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  2020.11 

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  12. Them1 Binds to Free Fatty Acids and is Allosterically Regulated by Lysophosphatidylcholine to Control Fatty Acyl-CoA Hydrolysis in Brown Adipose Tissue

    Tillman Matthew, Li Yue, Khadka Manoj, Imai Norihiro, Adhiyaman Akshitha, Juneja Puneet, Hagen Susan, Cohen David, Ortlund Eric

    FASEB JOURNAL  2020.4 

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  13. 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  2020.11 

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  14. Thioesterase Superfamily Member 1 Undergoes Stimulus-coupled Reorganization to Regulate Metabolic Activity in Brown Adipose Tissue

    Li Yue, Imai Norihiro, Goyal Samaksh, Nicholls Hayley, Krisko Tibor, Baqai Mahnoor, Ang Lay-Hong, Tillman Matthew, Ortlund Eric, Cohen David, Hagen Susan

    FASEB JOURNAL  2020.4 

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  15. Them1 Binds to Free Fatty Acids and is Allosterically Regulated by Lysophosphatidylcholine to Control Fatty Acyl-CoA Hydrolysis in Brown Adipose Tissue

    Tillman Matthew, Li Yue, Khadka Manoj, Imai Norihiro, Adhiyaman Akshitha, Juneja Puneet, Hagen Susan, Cohen David, Ortlund Eric

    FASEB JOURNAL  2020.4 

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  16. 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  2020.11 

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KAKENHI (Grants-in-Aid for Scientific Research) 3

  1. 臓器特異的なUBXD8の機能を主軸としたアルコール性肝障害の病態形成メカニズム

    Grant number:21KK0277  2021

    科学研究費助成事業  国際共同研究加速基金(国際共同研究強化(A))

    今井 則博

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    Authorship:Principal investigator 

    Grant amount:\15600000 ( Direct Cost: \12000000 、 Indirect Cost:\3600000 )

  2. アルコール性肝障害におけるUBXD8機能の解明

    Grant number:21K15946  2021.4 - 2025.3

    若手研究

    今井 則博

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    Authorship:Principal investigator 

    Grant amount:\4680000 ( Direct Cost: \3600000 、 Indirect Cost:\1080000 )

  3. マイオカインによる臓器相関に着目した新規NAFLD治療ターゲットの探索

    Grant number:20K22898  2020.9 - 2022.3

    日本学術振興会  科学研究費助成事業 研究活動スタート支援  研究活動スタート支援

    今井 則博

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    Authorship:Principal investigator 

    Grant amount:\2860000 ( Direct Cost: \2200000 、 Indirect Cost:\660000 )

    骨格筋はマイオカインと総称されるペプチドの分泌を通じて、肝臓を含む全身の代謝臓器との臓器間コミュニケーションにおいて重要な役割を果たしている。近年、研究代表者はマウスモデルにおいて骨格筋における脂肪酸のβ酸化が臓器を超えて脂肪肝、インスリン抵抗性、肥満の発症に関与していること、また骨格筋が代謝状態に応じて複数のマイオカインを分泌し肝臓からの超低密度リポタンパク質(VLDL)分泌を調節していることを明らかにした。これらの知見は骨格筋の脂肪酸代謝が全身の糖代謝、脂質代謝において重要な役割を果たしていること、骨格筋がマイオカインを通じて過栄養時の脂肪肝、肥満の発症に寄与していることを示唆している。

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