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Factors associated with the response to interferon-based antiviral therapies for chronic hepatitis C

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World Journal of Hepatology 2015年第26期7卷 2681-2687页

作者： Hirayuki Enomoto Shuhei nishiguchi Division of Hepato- biliary and Pancreatic Disease Department of Internal MedicineHyogo College of Medicine

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.

关键词： Anti-interferon-α neutralizing antibody Interferon

Body Characteristics of Professional Japanese Keirin Cyclists： Flexibility, Pelvic Tilt, and Muscle Strength

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Journal of Sports Science 2016年第6期4卷 341-345页

作者： Yuto Tashiro Satoshi Hasegawa Shu nishiguchi Naoto Fukutani Daiki Adachi Takayuki Hotta Saori Morino Hidehiko Shirooka Yuma Nozaki Hinako Hirata Moe Yamaguchi Seishiro Tasaka Tomohumi Matsushita Keisuke Matsubara Tomoki Aoyama Human Health Sciences Graduate School of Medicine Kyoto University Kyoto 606-8501 Japan Research Fellow of the Japan Society for the Promotion of Science Tokyo 102-0083 Japan

OBJECTIVE： To identify muscle imbalances and pelvic tilt with implications for low back pain in Keirin cyclists. METHODS： We enrolled 16 Keirin cyclists （mean age, 32.2 ±8.6 years） and 16 college students as controls （24.3 ± 2.3 years）. We measured pelvic tilt, heel-buttock distance （HBD）, iliopsoas flexibility （using the Thomas test）, hamstring flexibility （using the straight-leg-raise [SLR] test）, finger floor distance （FFD）, and isometric and isokinetic hamstring and quadriceps muscle strength. These parameters were compared between the two groups, as well as between the right and left sides, by using the Mann-Whitney U test or unpaired t test. RESULTS： The results of this study revealed a significant anterior pelvic tilt at standing position and significantly higher HBD, SLR, and FFD in the Keirin cyclists than in the controls. The isokinetic muscle strength of the quadrieeps and hamstring, and the hamstring-to-quadriceps ratio at high angular velocity were significantly greater in the Keirin cyclists. No significant differences were found between the right and left sides. CONCLUSION： This study revealed that the Keirin cyclists had an anterior pelvic tilt and imbalance in hip muscle flexibility, but the difference between the right and left sides were not significant.

关键词： Keirin pelvic tilt muscle flexibility imbalance.

巨大脑膜瘤栓塞后的敏感性改变:应用非增强磁敏感加权PRESTO、扩散加权及灌注加权成像进行多参数直方图分析

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国际医学放射学杂志 2013年第2期 202-203页

作者： T. nishiguchi T. Iwakiri K. Hayasaki M. Ohsawa T. Yoneda Y. Mitsuhash 赵芳 Department of Radiology Osaka City University Graduate School of Medicine 1-4-3 Asahimachi Abeno Osaka 545-8585 Japan

目的评估脑膜瘤栓塞后成像特征及磁敏感加权成像(SWI)是否可以显示肿瘤缺血。方法对16例病人(8例组织病理学显示缺血,8例无缺血)术前栓塞治疗前后的影像进行研究。确定每人整个肿瘤的层选择感兴趣区(slice-wiseROI),对比缺血组与非缺血... 详细信息

目的评估脑膜瘤栓塞后成像特征及磁敏感加权成像(SWI)是否可以显示肿瘤缺血。方法对16例病人(8例组织病理学显示缺血,8例无缺血)术前栓塞治疗前后的影像进行研究。确定每人整个肿瘤的层选择感兴趣区(slice-wiseROI),对比缺血组与非缺血组SW、表观扩散系数(ADC)、脑血容量(CBV)、脑血流量(CBF)、平均通过时间(MTT)及疾病进展时间(TTP)图的直方图变量[均值、标准差(SD)、最小值、最大值、直方图宽度、模式及峰值]。将SWI直方图的变化与组织病理学特征关联。结果缺血组SWI信号强度呈下降趋势,而非缺血组却呈部分上升。在ADC图上呈现类似表现。PWI直方图上显示缺血组MTT增加;两组间的CBV并无显著差异。微出血与SWI直方图峰值有一定关系。结论 SWI上T2*加权MR对比剂的栓塞后改变很大程度上与脱氧血红蛋白水平及动脉血流变化有关。要点①血管内栓塞现在是颅内脑膜瘤的辅助疗法。②MRI用来评价栓塞效果。③非增强敏感加权MRI可以显示缺血与非缺血区域。④SWI影像的信号改变与扩散及灌注异常有关。⑤三维高分辨力SWI提供了评价缺血的新影像指标。

关键词：磁敏感加权成像缺血缺氧脑膜瘤梗死

Elevation of the glycated albumin to glycated hemoglobin ratio during the progression of hepatitis C virus related liver fibrosis

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World Journal of Hepatology 2012年第1期4卷 11-17页

作者： 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 Division of Hepatobiliary and Pancreatic Disease Department of Internal Medicine Hyogo College of Medicine Department of Gasteroenterology Nissay Hospital

AIM: To analyze the relationship between the glycated albumin (GA) to glycated hemoglobin (HbA1c) ratio and the histological grading of liver ***: 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 3.0) was as follows: its sensitivity

关键词： Glycated albumin Glycated hemoglobin Liver fibrosis Liver biopsy Hepatitis C virus

Development of risky varices in alcoholic cirrhosis with a well-maintained nutritional status

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World Journal of Hepatology 2015年第21期7卷 2358-2362页

作者： Hirayuki Enomoto Yoshiyuki Sakai Yoshinori Iwata Ryo Takata Nobuhiro Aizawa Naoto Ikeda Kunihiro Hasegawa Chikage Nakano Takashi Nishimura Kazunori Yoh Akio Ishii Tomoyuki Takashima Hiroki Nishikawa Hiroko Iijima Shuhei nishiguchi Division of Hepatobiliary and Pancreatic Disease Department of Internal Medicine Hyogo College of Medicine

AIM: To compare the nutritional status between alcoholic compensated cirrhotic patients and hepatitis C virus(HCV)-related cirrhotic patients with portal ***: A total of 21 patients with compensated cirrhosis(14 with HCV-related cirrhosis and seven with alcoholic cirrhosis) who had risky esophageal varices were investigated. In addition to physical variables, including the body mass index, triceps skinfold thickness, and arm-muscle circumference, the nutritional status was also assessed using the levels of pre-albumin(pre-ALB), retinol-binding protein(RBP) and non-protein respiratory quotient(NPRQ) measured with an indirect ***: A general assessment for the nutritional status with physical examinations did not show a significant difference between HCV-related cirrhosis and alcoholic cirrhosis. However, the levels of pre-ALB and RBP in alcoholic compensated cirrhotic patients were significantly higher than those in HCV-related compensated cirrhotic patients. In addition, the frequency of having a normal nutritional status(NPRQ ≥ 0.85 and ALB value > 3.5 g/d L) in alcoholic compensated cirrhotic patients was significantly higher than that in HCV-related compensated cirrhotic ***: According to our small scale study, alcoholic compensated cirrhotic patients can develop severe portal hypertension even with a relatively well-maintained liver function and nutritional status compared with HCV-related cirrhosis.

关键词： Alcoholic liver cirrhosis Hepatitis C virus Rapid-

Survival of geriatric patients after percutaneous endoscopic gastrostomy in Japan

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World Journal of Gastroenterology 2010年第40期16卷 5084-5091页

作者： 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 Department of Surgery International Universi-ty of Health and Welfare Hospital Department of Molecular Epidemiology Jikei University School of Medicine Endoscopy Unit Iwate prefectural Central Hospital Department of Internal Medicine Tsuyama Chuo Hospital Department of Surgery Higashi Washi-nomiya Hospital Digestive Disease Center Showa Inan General Hospital Department of Neurology Ebina Medical Sup-port Center Department of Surgery Sumitomo Hospital Department of Gastroenterology Kiyota Hospital Department of Gastroenterology Okano Clinic Department of Geriatrics Hitachikoh Hospital Department of Internal Medicine Jomoto Gastroenteric and Internal Medical Clinic Department of Surgery Fujiyoshida Munici-pal Hospital 2nd Department of Surgery Wakayama Medical University Hospital Department of Surgery Tokatsu-clinic Hospital Department of Surgery Kure Kyosai Hospital Department of Internal Medicine Matsue Sei-kyo Genaral Hospital Department of Gastroenterology Hirano General Hospital Department of Internal Medicin Nara Prefectural Gojo Hospital Department of Internal Medicine Isesaki Mu-nicipal Hospital Department of Internal Medicine Muraka-mi Memorial Hospital Digestive Endoscopy Center Sendai Kousei Hospital Department of Surgery Onishi Hospital Department of Surgery Tokyo Metropoli-tan Ohkubo Hospital Department of Internal Medicine Tsuruoka Kyoritsu Hospital Nutritional Therapy Center Toho Uni-versity Omori Medical Center Home Care Department Kameda Medical Hospital Endoscopic Treatment Center Japan Labour Health and Welfare Organization Niigata Rousai Hospital Department of Gastroenterology and Hepatology Social Insurance Shimonoseki Welfare Hospital Department of Gastroenterology Ako City Hospital Percutaneous Endoscopic Gastrostomy Center Oita Kensei Hospital Department of Internal Medicine Nishimino Kosei Hospital Department of Pediatric Surgery Nagano Red Cross Hospital Department of Internal Medicine Sapporo Shirakaba-dai hospital Department of Gastroenterology Tachikawa

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.

关键词： Percutaneous endoscopic gastrostomy Enteral nutrition Comorbidity Survival Risk factor

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美国医学会眼科杂志（中文版） 2004年第4期16卷 245-245页

作者： GeraldA.Fishman MaryFlynnRoberts DeborahJ.Derlacki JonnaL.Grimsby HiroyukiYamamoto DrorSharon KojiM.nishiguchi ThaddeusP.Dryja 齐越

目的：在来自3个家族中的5例患者中评价与白色斑点性视网膜炎(RPA)的分子遗传学缺陷。方法：我们检查了患有RPA的3例先证者和2例临床受累者。临床检查包括最佳视力检查，视野检查，视网膜电图检查，双眼眼底检查和眼底照相。对白细胞的... 详细信息

目的：在来自3个家族中的5例患者中评价与白色斑点性视网膜炎(RPA)的分子遗传学缺陷。方法：我们检查了患有RPA的3例先证者和2例临床受累者。临床检查包括最佳视力检查，视野检查，视网膜电图检查，双眼眼底检查和眼底照相。对白细胞的DNA进行分析，在基因编码细胞retinaldehyde-黏连蛋白1(RLBP1)，11-cis-视黄醇脱氢酶中(RDH5)，(RBP3)，光感受器之间的类维生素黏连蛋白(RBP3)和光感受器全反视黄醇脱氢醇(RDH8)的外显子中找到突变。不是所有的患者都进行了全部基因的突变评估。外显子通过单链构象多态性分析或直接基因测序被分别的倍增和筛选，以寻找突变。

关键词：突变视网膜炎眼底改变 RBP 患者细胞视黄醇外显子蛋白家族