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| 1 | Liver fibrosis markers of nonalcoholic steatohepatitis显示文摘Nonalcoholic fatty liver disease(NAFLD) is one of themajor causes of chronic liver injury. NAFLD includes a wide range of clinical conditions from simple steatosis to nonalcoholic steatohepatitis(NASH), advanced fibrosis, and liver cirrhosis. The histological findings of NASH indicate hepatic steatosis and inflammation with characteristic hepatocyte injury(e.g., ballooning degeneration), as is observed in the patients with alcoholic liver disease. NASH is considered to be a potentially health-threatening disease that can progress to cirrhosis. A liver biopsy remains the most reliable diagnostic method to appropriately diagnose NASH, evaluate the severity of liver fibrosis, and determine the prognosis and optimal treatment. However, this invasive technique is associated with several limitations in routine use, and a number of biomarkers have been developed in order to predict the degree of liver fibrosis. In the present article, we review the current status of noninvasive biomarkers available to estimate liver fibrosis in the patients with NASH. We also discuss our recent findings on the use of the glycated albuminto-glycated hemoglobin ratio, which is a new index that correlates to various chronic liver diseases, including NASH. | Hirayuki Enomoto Yukihiro Bando Hideji Nakamura Shuhei Nishiguchi Masafumi Koga | 2015 | World Journal of Gastroenterology2015，21，24： | 12 |
| 2 | Elevation of the glycated albumin to glycated hemoglobin ratio during the progression of hepatitis C virus related liver fibrosis显示文摘AIM: To analyze the relationship between the glycated albumin (GA) to glycated hemoglobin (HbA1c) ratio and the histological grading of liver fibrosis.METHODS: The study retrospectively included consecutive hepatitis C virus positive chronic liver disease patients (n = 142) who had undergone percutaneous liver biopsy between January 2008 and March 2010 at our institution. The ratios of GA/HbA1c were calculated in all patients to investigate the relationship with the degree of the liver fibrosis. The values of the aspartate aminotransferase-to-platelet ratio index (APRI), an excellent marker for the evaluation of liver fibrosis, were also calculated. In addition, we combined the ratio of GA/HbA1c and the APRI in order to improve our ability to detect the presence of significant liver fibrosis. RESULTS: Sixty-one (43%) patients had either no fibrosis or minimal fibrosis (METAVIR score: F0-F1), while 25 (17%) had intermediate fibrosis (F2). Fifty-six (39%) patients had severe fibrosis (F3-F4) and 27 of them had cirrhosis (F4). The mean values of the GA/HbA1c increased with the progression of the fibrosis (F0-1: 2.83 ± 0.24, F2: 2.85 ± 0.24, F3: 2.92 ± 0.35, F4: 3.14 ± 0.54). There was a significant dif- ference between the F0-F1 vs F4, F2 vs F4, and F3 vs F4 groups (P < 0.01, P < 0.01, P < 0.01 and P < 0.05, respectively). The GA/HbA1c ratio was significantly higher in the patients with cirrhosis (F4) than in those without cirrhosis (F0-F3) (3.14 ± 0.54 vs 2.85 ± 0.28, P < 0.0001). The GA/HbA1c ratio was also significantly higher in the patients with severe fibrosis (F3-F4) than in those without severe liver fibrosis (F0-F2) (3.03 ± 0.41 vs 2.84 ± 0.24, P < 0.001). Furthermore, the GA/ HbA1c ratio was also significantly higher in the patients with significant fibrosis (F2-F4) than in those without significant liver fibrosis (F0-F1) (2.98 ± 0.41 vs 2.83 ± 0.24, P < 0.001). The diagnostic performance of the increased GA/HbA1c ratio (> 3.0) was as follows: its sensitivity and specificity for the detection of liver cirrhosis (F4) were 59.3% and 70.4%, respectively and its sensitivity and specificity for the detection of severe liver fibrosis (F3-F4) were 50.0% and 74.4%,respectively. With regard to the detection of significant fibrosis (F2-F4), its sensitivity was 44.4% and its specificity was 77.0%. Although even the excellent marker APRI shows low sensitivity (25.9%) for distinguishing patients with or without significant fibrosis, the combination of the APRI and GA/HbA1c ratio increased the sensitivity up to 42.0%, with only a modest decrease in the specificity (from 90.2% to 83.6%). CONCLUSION: The GA/HbA1c ratio increased in line with the histological severity of liver fibrosis, thus suggesting that this ratio is useful as a supportive index of liver fibrosis. | Nobuhiro Aizawa Hirayuki Enomoto Hiroyasu Imanishi Masaki Saito Yoshinori Iwata Hironori Tanaka Naoto Ikeda Yoshiyuki Sakai Tomoyuki Takashima Takashi Iwai Ei-ichiro Moriwaki Soji Shimomura Hiroko Iijima Hideji Nakamura Shuhei Nishiguchi | 2012 | World Journal of Hepatology2012，4，1： | 10 |
| 3 | Proton pump inhibitor induced collagen expression in colonocytes is associated with collagenous colitis显示文摘AIM To elucidate the role of proton pump inhibitors(PPIs) in collagenous disease, direct effect of PPI on colonocytes was examined.METHODS Collagenous colitis is a common cause of non-bloody, watery diarrhea. Recently, there has been increasing focus on the use of proton PPIs as a risk factor for developing collagenous colitis. Mouse CT26 colonic cells were treated with PPI and/or PPI-induced alkaline media. Expression of fibrosis-associated genes was examined by RT-PCR. In human materials, collagen expression was examined by immunohistochemistry.RESULTS CT26 cells expressed a Na+-H+ exchanger gene(solute carrier family 9, member A2). Treatment with PPI and/or PPI-induced alkaline media caused growth inhibition and oxidative stress in CT26 cells. The treatment increased expression of fibrosis inducing factors, transforming growth factor β and fibroblast growth factor 2. The treatment also decreased expression of a negative regulator of collagen production, replication factor C1, resulting in increased expression of collagen types Ⅲ and Ⅳ in association with lipid peroxide. In biopsy specimens from patients with collagenous colitis, type Ⅲ and Ⅳ collagen were increased. Increase of type Ⅲ collagen was more pronounced in PPI-associated collagenous colitis than in non-PPI-associated disease. CONCLUSION From these findings, the reaction of colonocytes to PPI might participate in pathogenesis of collagenous colitis. | Shiori Mori Yui Kadochi Yi Luo Rina Fujiwara-Tani Yukiko Nishiguchi Shingo Kishi Kiyomu Fujii Hitoshi Ohmori Hiroki Kuniyasu | 2017 | World Journal of Gastroenterology2017，23，9： | 5 |
| 4 | Plasma brain natriuretic peptide level in older outpatients with heart failure is associated with physical frailty, especially with the slowness domain显示文摘ObjectiveTo 决定在血浆大脑 natriuretic 之间的协会在有心失败( HF )和物理脆弱以及与心血管的药的 106 个门诊病人变老的物理 frailty.MethodsTwo 的每个领域的病人的肽( BNP )水平60岁以上为 HF 被就医了或被给了一为 HF 的药方药被包括。物理脆弱用下列五个领域被估计:缓慢,软弱,疲劳,低活动,并且缩小,根据心血管的健康学习。病人们根据脆弱分数被划分成 nonfrailty 和脆弱组。血浆 BNP 水平被测量。6-min 散步测试被执行测量 endurance.ResultsPlasma BNP 在二个组之间是显著地不同的(脆弱组:158.0 ±214.7 pg/mL, nonfrailty 组:65.2 ±88.0 pg/mL, P <0.01 ) 。Multivariate 逻辑回归分析表明转变木头的血浆 BNP (木头 BNP ) 显著地与物理脆弱被联系(或:1.68, 95% CI:1.11-2.56 ) ,并且木头 BNP 显著地与缓慢领域被联系(走的速度 <1.0 m/s ) 物理脆弱(或:1.75, 95% CI:1.15-2.67 ) 。另外,木头 BNP 否定地被相关到 6 分钟的散步距离(6MWD )(ρ=− 0.37, P <0.01 ) ,当 6MWD 断然被相关到走速度时(ρ= 0.66, P <0.01 ).ConclusionsPlasma BNP 水平与物理脆弱有关,特别在缓慢领域。耐力可以在在血浆 BNP 水平和走的速度之间的协会干涉。 | Shu Nishiguchi Yuma Nozaki Masayuki Yamaji Kanako Oya Yuki Hikita Tomoki Aoyama Hiroshi Mabuchi | 2016 | Journal of Geriatric Cardiology2016，13，7： | 5 |
| 5 | Serial changes in expression of functionally clustered genes in progression of liver fibrosis in hepatitis C patients显示文摘AIM: To investigate the relationship of changes in expression of marker genes in functional categories or molecular networks comprising one functional category or multiple categories in progression of hepatic fibrosis in hepatitis C (HCV) patients. METHODS: Marker genes were initially identified using DNA microarray data from a rat liver fibrosis model. The expression level of each fibrosis associated marker gene was analyzed using reverse transcription-polymerase chain reaction (RT-PCR) in clinical biopsy specimens from HCV-positive patients (n = 61). Analysis of changes in expression patterns and interactions of marker genes in functional categories was used to assess the biological mechanism of fibrosis. RESULTS: The profile data showed several biological changes associated with progression of hepatic fibrosis. Clustered genes in functional categories showed sequential changes in expression. Several sets of clustered genes, including those related to the extracellular matrix (ECM), inflammation, lipid metabolism, steroid metabolism, and some transcription factors important for hepatic biology showed expression changes in the immediate early phase (F1/F2) of fibrosis. Genes associated with aromatic amino acid (AA) metabolism, sulfur-containing AA metabolism and insulin/ Wnt signaling showed expression changes in the middle phase (F2/F3), and some genes related to glucose metabolism showed altered expression in the late phase of fibrosis (F3/F4). Therefore, molecular networks showing serial changes in gene expression are present in liver fibrosis progression in hepatitis C patients. CONCLUSION: Analysis of gene expression profiles from a perspective of functional categories or molecular networks provides an understanding of disease and suggests new diagnostic methods. Selected marker genes have potential utility for biological identification of advanced fibrosis. | Yoshiyuki Takahara Mitsuo Takahashi Qing-Wei Zhang Hirotaka Wagatsuma Maiko Mori Akihiro Tamori Susumu Shiomi Shuhei Nishiguchi | 2008 | World Journal of Gastroenterology2008，14，13： | 4 |
| 6 | Survival of geriatric patients after percutaneous endoscopic gastrostomy in Japan显示文摘AIM: To examine the long term survival of geriatric patients treated with percutaneous endoscopic gastrostomy (PEG) in Japan. METHODS: We retrospectively included 46 Japanese community and tertiary hospitals to investigate 931 consecutive geriatric patients (≥ 65 years old) with swallowing difficulty and newly performed PEG between Jan 1st 2005 and Dec 31st 2008. We set death as an outcome and explored the associations among patient’s characteristics at PEG using log-rank tests and Cox proportional hazard models. RESULTS: Nine hundred and thirty one patients were followed up for a median of 468 d. A total of 502 deaths were observed (mortality 53%). However, 99%, 95%, 88%, 75% and 66% of 931 patients survived more than 7, 30, 60 d, a half year and one year, respectively. In addition, 50% and 25% of the patients survived 753 and 1647 d, respectively. Eight deaths were considered as PEG-related, and were associated with lower serum albumin levels (P = 0.002). On the other hand, among 28 surviving patients (6.5%), PEG was removed. In a multivariate hazard model, older age [hazard ratio (HR), 1.02; 95% confidence interval (CI), 1.00-1.03; P = 0.009], higher C-reactive protein (HR, 1.04; 95% CI: 1.01-1.07; P = 0.005), and higher blood urea nitrogen (HR, 1.01; 95% CI: 1.00-1.02; P = 0.003) were significant poor prognostic factors, whereas higher albumin (HR, 0.67; 95% CI: 0.52-0.85; P = 0.001), female gender (HR, 0.60; 95% CI: 0.48-0.75; P < 0.001) and no previous history of ischemic heart disease (HR, 0.69; 95% CI: 0.54-0.88, P = 0.003) were markedly better prognostic factors. CONCLUSION: These results suggest that more than half of geriatric patients with PEG may survive longer than 2 years. The analysis elucidated prognostic factors. | Yutaka Suzuki Seryna Tamez Akihiko Murakami Akihiko Taira Akihiro Mizuhara Akira Horiuchi Chie Mihara Eiji Ako Hirohito Muramatsu Hitoshi Okano Hitoshi Suenaga Kazuaki Jomoto Junya Kobayashi Katsunari Takifuji Kazuhiro Akiyama Koh Tahara Koji Onishi Makoto Shimazaki Masami Matsumoto Masashi Ijima Masato Murakami Masato Nakahori Michiaki Kudo Michio Maruyama Mikako Takahashi Naohiro Washizawa Shigeru Onozawa Satoshi Goshi Satoyoshi Yamashita Shigeki Ono Shin Imazato Shinji Nishiwaki Shuichirou Kitahara Takao Endo Takao Iiri Takeshi Nagahama Takuto Hikichi Tatsuya Mikami Tetsuo Yamamoto Tetsushi Ogawa Tomoko Ogawa Tomoyuki Ohta Toshifumi Matsumoto Toshiroh Kura Tsutomu Kikuchi Tsuyoshi Iwase Tsuyotoshi Tsuji Yukio Nishiguchi Mitsuyoshi Urashima | 2010 | World Journal of Gastroenterology2010，16，40： | 4 |
| 7 | Factors associated with the response to interferon-based antiviral therapies for chronic hepatitis C显示文摘Hepatitis C virus(HCV) infection is a major health concern worldwide. Interferon-α(IFN-α) therapy has been the main antiviral treatment for more than 20 years. Because of its established antitumor effects, IFNbased treatments for chronic HCV infection still have a clinical impact, particularly for patients with high risk conditions of developing hepatocellular carcinoma, such as older age and advanced liver fibrosis. As a result of exhaustive research, several viral factors, including NS5 A amino acid mutations such as the IFN sensitivitydetermining region and the IFN/ribavirin resistancedetermining region, and mutations of amino acids in the core protein region(core 70 and 91) were shown to be associated with the response to IFN-α treatment. In addition, among the host factors related to the response to IFN-α treatment, polymorphisms of the interleukin-28 B gene were identified to be the most important factor. In this article, we review the factors associated with the efficacy of IFN-α treatment for chronic HCV infection. In addition, our recent findings regarding the possible involvement of anti-IFN-α neutralizing antibodies in a non-response to pegylated-IFN-α treatment are also described. | Hirayuki Enomoto Shuhei Nishiguchi | 2015 | World Journal of Hepatology2015，7，26： | 3 |
| 8 | Small target detection from image sequences using recursive max filter 显示文摘 | NISHIGUCHI K KOBAYASHI M ICHIKAWA A | 1995 | SPIE1995，2561，： | 2 |
| 9 | Serum Cytokeratin 19 Fragment (CYFRA21-1) as a Prognostic Factor in Intrahepatic Cholangiocarcinoma显示文摘 | Takahiro Uenishi MD Osamu Yamazaki MD Hiromu Tanaka MD Shigekazu Takemura MD Takatsugu Yamamoto MD Shogo Tanaka MD Shuhei Nishiguchi MD Shoji Kubo MD | 2008 | Annals of Surgical Oncology2008，，2： | 2 |
| 10 | Improved algorithm for estimating pulse repetition intervals 显示文摘 | Nishiguchi K and Kobayashi M | 2000 | IEEE Transactions on Aerospace and Electronic Systems2000，36，2： | 1 |
| 11 | Clinical usefulness of carcinoembryonic antigen measurement in nipple discharge as an adjunctive tool for diagnosis of breast cancer显示文摘 | NISHIGUCHI T HISHIMOTO T FUNAHASHI S | 1992 | Rinsho Byori1992，40，1： | 1 |
| 12 | Improved Algorithm for Estimating Pulse Repetiton Intervals 显示文摘 | Ken'Ichi Nishiguchi Masaaki Kobayashi | 2000 | IEEE Transactions on Aerospace and Electronic Systems2000，36，2： | 1 |
| 13 | Improved algorithm for estimating pulse repetition intervals 显示文摘 | Nishiguchi K Kobayashi M | 2000 | IEEE Transactions on Aerospace and Electronic Systems2000，36，2： | 1 |
| 14 | Effects of polymerization method on structure and properties of thermoplastic polyurethanes 显示文摘 | YAMASAKI S NISHIGUCHI D KOJIO K | 2007 | J Polym Sci Part B: Polym Phys2007，45，7： | 1 |
| 15 | Photocatalytic reduction of CO, with H2O on TiO2 and Cu/TiO2 catalysts 显示文摘 | Yamashita H Nishiguchi H Kamada N | 1994 | Res Chem Intermed1994，20，8： | 1 |
| 16 | Steam reforming of dimethyl ether over H-mordenite-Cu/CeO2 catalysts显示文摘 | Matsumoto T Nishiguchi T Kanai H | 2004 | Applied Catalysis A:General2004，276，12： | 1 |
| 17 | cathodic performance of VOPO4 with various crystals phases for Li-ion rechargeable battery显示文摘 | BUSTAM M A ISHIHARA T NISHIGUCHI H | 2002 | Electrochimica Acta2002，48，： | 1 |
| 18 | Randomized clinical tri- al of long-term outcome after resection of hepatitis C virus-relat- ed hepatocellular carcinoma by postoperative interferon therapy 显示文摘 | Kubo S Nishiguchi S Hirohashi K | 2002 | Br J Surg2002，89，4： | 1 |
| 19 | Etiology of liver cirrhosis in Japan:a nationwide survey显示文摘 | Michitaka K Nishiguchi S Aoyagi Y | | 0，，01： | 1 |
| 20 | Improved Algorithm for Estimating Pulse Repetition Intervals 显示文摘 | KENICHI NISHIGUCHI MASAAKI KOBAYASHI | 2000 | IEEE Trans on AES2000，36，2： | 1 |
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