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乙型肝炎病毒抗原的组合使用预测对核苷酸(t)类似物/聚乙 [复制链接]

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发表于 2018-2-5 19:36 |只看该作者 |倒序浏览 |打印
Journal of Gastroenterology

February 2018, Volume 53, Issue 2, pp 247–257 | Cite as
Combinational use of hepatitis B viral antigens predicts responses to nucleos(t)ide analogue/peg-interferon sequential therapy

    Authors
    Authors and affiliations

    Akihiro MatsumotoShuhei NishiguchiHirayuki EnomotoJong-Hon KangYasuhito TanakaNoboru ShinkaiMasayuki KurosakiMasaru EnomotoTatsuo KandaOsamu YokosukaHiroshi YatsuhashiShinya NagaokaChiaki OkuseTatehiro KagawaTetsuya MineKoichi TakaguchiSatoru SaitoKeisuke HinoFusao IkedaShotaro SakisakaDaisuke MoriharaShiho MiyaseMasataka TsugeKazuaki ChayamaNaoki HiramatsuYoshiyuki SuzukiKazumoto MurataEiji TanakaEmail author

    Akihiro Matsumoto
        1
    Shuhei Nishiguchi
        2
    Hirayuki Enomoto
        2
    Jong-Hon Kang
        3
    Yasuhito Tanaka
        4
    Noboru Shinkai
        4
    Masayuki Kurosaki
        5
    Masaru Enomoto
        6
    Tatsuo Kanda
        7
    Osamu Yokosuka
        7
    Hiroshi Yatsuhashi
        8
    Shinya Nagaoka
        8
    Chiaki Okuse
        9
    Tatehiro Kagawa
        10
    Tetsuya Mine
        10
    Koichi Takaguchi
        11
    Satoru Saito
        12
    Keisuke Hino
        13
    Fusao Ikeda
        14
    Shotaro Sakisaka
        15
    Daisuke Morihara
        15
    Shiho Miyase
        16
    Masataka Tsuge
        17
    Kazuaki Chayama
        17
    Naoki Hiramatsu
        18
    Yoshiyuki Suzuki
        19
    Kazumoto Murata
        2021
    Eiji Tanaka
        1Email authorView author's OrcID profile

    1.Department of MedicineShinshu University School of MedicineMatsumotoJapan
    2.Division of Hepatobiliary and Pancreatic Disease, Department of Internal MedicineHyogo College of MedicineNishinomiyaJapan
    3.Center for GastroenterologyTeine Keijinkai HospitalSapporoJapan
    4.Department of Virology and Liver UnitNagoya City University Graduate School of Medical SciencesNagoyaJapan
    5.Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
    6.Department of HepatologyOsaka City University Medical SchoolOsakaJapan
    7.Department of Gastroenterology and Nephrology, Graduate School of MedicineChiba UniversityChibaJapan
    8.The Clinical Research CenterNational Hospital Organization Nagasaki Medical CenterOmuraJapan
    9.Division of Gastroenterology and Hepatology, Department of Internal MedicineSt. Marianna University School of MedicineKawasakiJapan
    10.Division of Gastroenterology, Department of Internal MedicineTokai University School of MedicineIseharaJapan
    11.Department of HepatologyKagawa Prefectural Central HospitalTakamatsuJapan
    12.Department of Gastroenterology and HepatologyYokohama City University School of MedicineYokohamaJapan
    13.Department of Hepatology and PancreatologyKawasaki Medical SchoolKurashikiJapan
    14.Department of Gastroenterology and HepatologyOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesOkayamaJapan
    15.Department of Gastroenterology and MedicineFukuoka University Faculty of MedicineFukuokaJapan
    16.Department of Gastroenterology and HepatologyKumamoto Shinto General HospitalKumamotoJapan
    17.Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health SciencesHiroshima UniversityHiroshimaJapan
    18.Department of GastroenterologyOsaka Rosai HospitalSakaiJapan
    19.Department of HepatologyToranomon HospitalTokyoJapan
    20.The Research Center for Hepatitis and ImmunologyNational Center for Global Health and MedicineIchikawaJapan
    21.Department of Gastroenterology, Graduate School of Medical SciencesInternational University of Health and WelfareNaritaJapan

Original Article—Liver, Pancreas, and Biliary Tract
First Online: 20 June 2017
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Abstract
Background

This prospective cohort study searched for factors associated with a response to nucleos(t)ide analogue/peg-interferon (NUC/peg-IFN) sequential therapy.
Methods

A total of 95 patients with chronic hepatitis B being treated with NUCs were enrolled. Immediately following NUC cessation, peg-IFN was administered at 180 µg/dose weekly for 48 weeks.
Results

Twenty-six patients (27%) were judged to be responders at 48 weeks after the completion of peg-IFN. Analysis of baseline factors revealed that hepatitis B surface antigen (HBsAg) <3.1 log IU/ml and HB core-related antigen (HBcrAg) <3.9 log U/ml were significant indicators of a treatment response. The levels of the markers decreased in both responders and non-responders during peg-IFN therapy but continued falling in responders only after halting peg-IFN. Lower HBsAg (<2.0 log IU/ml) and HBcrAg (<3.8 log U/ml) levels at the time of response judgment were also significantly associated with a favorable response. While lower HBcrAg at baseline was the sole predictor of decreased HBcrAg levels at judgment, lower HBsAg, lower HBcrAg, and the use of adefovir dipivoxil at baseline predicted decreased HBsAg levels at the study endpoint. The use of adefovir dipivoxil was also associated with higher serum IFN-λ3, which might have contributed to the reduction in patient HBsAg levels.
Conclusions

The combinational use of HBsAg and HBcrAg levels at baseline and their changes throughout sequential therapy may be useful for predicting a response to NUC/peg-IFN sequential therapy.
Keywords
Hepatitis B surface antigen Hepatitis B core-related antigen Covalently closed circular DNA Chronic hepatitis Anti-viral therapy

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发表于 2018-2-5 19:37 |只看该作者
胃肠病学杂志

2018年2月,第53卷,第2期,第247-257页引用为
乙型肝炎病毒抗原的组合使用预测对核苷酸(t)类似物/聚乙二醇干扰素序贯疗法

    作者
    作者和从属关系

    彰MatsumotoShuhei NishiguchiHirayuki EnomotoJong翰KangYasuhito TanakaNoboru ShinkaiMasayuki KurosakiMasaru EnomotoTatsuo KandaOsamu YokosukaHiroshi YatsuhashiShinya NagaokaChiaki OkuseTatehiro KagawaTetsuya MineKoichi TakaguchiSatoru SaitoKeisuke HinoFusao IkedaShotaro SakisakaDaisuke MoriharaShiho MiyaseMasataka TsugeKazuaki ChayamaNaoki HiramatsuYoshiyuki SuzukiKazumoto MurataEiji TanakaEmail作者

    松本明弘
        1
    Shuhei西口
        2
    Hirayuki Enomoto
        2
    姜钟汉
        3
    Yasuhito田中
        4
    Noboru Shinkai
        4
    Masayuki Kurosaki
        五
    Masaru Enomoto
        6
    神田达夫
        7
    Osamu横须贺
        7
    八桥浩史
        8
    Shinya Nagaoka
        8
    千秋Okuse
        9
    香川圣宏
        10
    Tetsuya矿
        10
    Koichi Takaguchi
        11
    Satoru Saito
        12
    Keisuke Hino
        13
    池田富嫂
        14
    Sakisaka太郎
        15
    森原大介
        15
    Shiho Miyase
        16
    Masataka Tsuge
        17
    茶山昭山
        17
    直木直树
        18
    铃木吉幸
        19
    村本和本
        2021
    Eiji Tanaka
        1电子邮件authorView作者的OrcID配置文件

    1.日本松原大学医学部医学部
    2.肝胆胰疾病分类内科河津医科大学西宫日本
    3,消化科Teijo Keijinkai Hospital日本
    4.病毒学与肝病学系名古屋市立大学医学研究科名古屋大学日本
    五,消化病与肝病学部白宫红十字会医院东京日本
    大阪市大学医学部大阪市肝病科
    7.芝加哥大学医学研究院消化内科学士日本
    8.临床研究中心国立医院组织长崎医疗中心日本
    9.胃肠病学与肝病学系,内科学系。玛丽安娜大学医学院川崎日本
    10.胃肠病科,内科东京大学医学部伊朗日本
    香川县K川县立中央医院川崎医科大学
    12.消化内科横滨市立大学医学部横滨日本
    13.肝脏病学与胰腺病学川崎医学院仓敷日本
    14.胃肠病学与肝病学山冈大学医学研究科牙医学研究科日本山冈
    15.消化病医学科福冈大学医学部福冈日本
    16.胃肠病学与肝病学熊本神社综合医院熊本日本
    17.生物医学与健康科学研究所消化与代谢研究所应用生命科学广岛大学广岛日本
    18.胃肠病学大阪罗塞伊医院日本
    19,日本
    20.肝炎和免疫学研究中心国际全球卫生与医学中心IchikawaJapan
    21.医学科学研究生院消化内科国际健康与福利大学日本分校

原始文章肝脏,胰腺和胆道
首次在线:2017年6月20日
重印和权限

    301下载

抽象
背景

这项前瞻性队列研究寻找与核苷(t)ide类似物/ peg-干扰素(NUC / peg-IFN)顺序治疗反应有关的因素。
方法

共有95名慢性乙型肝炎患者接受NUCs治疗。紧接NUC停止后,peg-IFN每周以180μg/剂量给药48周。

结果

在peg-IFN完成后的48周,26名患者(27%)被判定为有反应者。基线因素分析显示,乙型肝炎表面抗原(HBsAg)<3.1 log IU / ml和HB核心相关抗原(HBcrAg)<3.9 log U / ml是治疗反应的显着指标。 peg-IFN治疗期间,应答者和非应答者中标志物的水平均下降,但仅在停止peg-IFN之后才响应者持续下降。反应判断时HBsAg(<2.0 log IU / ml)和HBcrAg(<3.8 log U / ml)水平也与有利的反应显着相关。虽然基线时HBcrAg较低是判断HBcrAg水平下降的唯一预测指标,但HBsAg下降,HBcrAg下降,基线时使用阿德福韦酯可预测研究终点HBsAg水平下降。阿德福韦酯的使用也与更高的血清IFN-λ3相关,这可能导致患者HBsAg水平降低。
结论

基线时HBsAg和HBcrAg水平的组合使用及其在序贯疗法中的变化对于预测对NUC / peg-IFN序贯疗法的响应可能是有用的。
关键词
乙型肝炎表面抗原乙型肝炎核心相关抗原共价闭合环状DNA慢性肝炎抗病毒治疗
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