恩替卡韦治疗日本的核苷（t）ide类似初治慢性乙型肝炎患者

StephenW

Journal of Gastroenterology

February 2019, Volume 54, Issue 2, pp 182–193 | Cite as
Long-term outcome of entecavir treatment of nucleos(t)ide analogue-naïve chronic hepatitis B patients in Japan

    Authors
    Authors and affiliations

    Fumitaka SuzukiEmail authorTetsuya HosakaYoshiyuki SuzukiHitomi SezakiNorio AkutaShunichiro FujiyamaYusuke KawamuraMasahiro KobayashiSatoshi SaitohYasuji AraseKenji IkedaMariko KobayashiRie MinetaYukiko SuzukiHiromitsu Kumada

    Fumitaka Suzuki
        12Email author
    Tetsuya Hosaka
        1
    Yoshiyuki Suzuki
        1
    Hitomi Sezaki
        1
    Norio Akuta
        1
    Shunichiro Fujiyama
        1
    Yusuke Kawamura
        1
    Masahiro Kobayashi
        1
    Satoshi Saitoh
        1
    Yasuji Arase
        1
    Kenji Ikeda
        1
    Mariko Kobayashi
        3
    Rie Mineta
        3
    Yukiko Suzuki
        3
    Hiromitsu Kumada
        1

    1.Department of HepatologyToranomon HospitalTokyoJapan
    2.Okinaka Memorial Institute for Medical ResearchTokyoJapan
    3.Research Institute for HepatologyToranomon Branch HospitalKawasakiJapan

Original Article—Liver, Pancreas, and Biliary Tract
First Online: 22 August 2018


Abstract
Background

We determined the antiviral potency and viral breakthrough rate after 10 years of continuous entecavir treatment in patients with chronic hepatitis B (CHB) infection.
Methods

The cumulative rates of undetectable hepatitis B virus DNA (HBV-DNA, < 2.1 log copies/mL), alanine aminotransferase (ALT) normalization, hepatitis B e antigen (HBeAg) seroclearance, hepatitis B surface antigen (HBsAg) seroclearance, and viral breakthrough of 1094 nucleos(t)ide analogue-naïve CHB patients (HBeAg-positive: 47%) who were on continuous entecavir treatment for 10 years were calculated.
Results

The median age was 50 years and follow-up period was 5.5 years, with 999, 804, 591, 390, 182 and 87 patients followed up for at least 1, 3, 5, 7, 9 and 10 years, respectively. Incremental increases were noted in the rates of undetectable HBV-DNA, ALT normalization, HBeAg seroclearance, and HBsAg seroclearance, reaching 96, 79, 38 and 3.7%, respectively, by the tenth year. The mean decline in HBsAg level from baseline was − 0.08 log IU/mL/year. Multivariate analysis identified HBsAg level and genotype (A) as independent predictors of HBsAg seroclearance. Sixteen patients experienced viral breakthrough. The cumulative percentages of patients with viral breakthrough analyzed by the Kaplan–Meier test were 1.5 and 2.5% at years 5 and 10, respectively. There were no serious adverse events during treatment.
Conclusions

Long-term entecavir treatment of nucleos(t)ide analogue-naïve CHB patients was associated with an excellent viral response and a low rate of entecavir-resistant mutations at 10 years. Baseline HBsAg levels and genotype were predictors of HBsAg seroclearance during entecavir treatment.
Keywords
Hepatitis B virus Entecavir HBsAg seroclearance Resistance Viral breakthrough

StephenW

消化内科杂志

2019年2月，第54卷，第2期，第182-193页引用为
恩替卡韦治疗日本的核苷（t）ide类似初治慢性乙型肝炎患者的远期疗效

    作者
    作者和附属机构

    Fumitaka SuzukiEmail authorTetsuya HosakaYoshiyuki SuzukiHitomi SezakiNorio AkutaShunichiro FujiyamaYusuke KawamuraMasahiro KobayashiSatoshi SaitohYasuji AraseKenji IkedaMariko KobayashiRie MinetaYukiko SuzukiHiromitsu Kumada

    Fumitaka Suzuki
        12Email作者
    Tetsuya Hosaka
        1
    Yoshiyuki Suzuki
        1
    Hitomi Sezaki
        1
    Norio Akuta
        1
    Shunichiro Fujiyama
        1
    川村雄介
        1
    Masahiro Kobayashi
        1
    斋藤聪
        1
    Yasuji Arase
        1
    Kenji Ikeda
        1
    Mariko Kobayashi
        3
    Rie Mineta
        3
    Yukiko Suzuki
        3
    Hiromitsu Kumada
        1

    1.Toranomon HospitalTokyoJapan，Hepatology of Hepatology
    2.Okinaka纪念医学研究所东京日本
    3.肝病学研究所虎之门分院医院川崎日本

原始文章 - 肝脏，胰腺和胆道
首次在线：2018年8月22日


抽象
背景

我们确定了慢性乙型肝炎（CHB）感染患者连续使用恩替卡韦10年后的抗病毒效力和病毒突破率。
方法

不可检测的乙型肝炎病毒DNA（HBV-DNA，<2.1 log拷贝/ mL），丙氨酸氨基转移酶（ALT）正常化，乙型肝炎e抗原（HBeAg）血清清除，乙型肝炎表面抗原（HBsAg）血清清除和病毒突破的累积率计算1094个核苷（t）ide类似物初始CHB患者（HBeAg阳性：47％），他们接受连续恩替卡韦治疗10年。
结果

中位年龄为50岁，随访期为5。5年，999,804,591,390,182和87例患者分别随访至少1年，3年，5年，7年，9年和10年。 HBV-DNA检测不到，ALT正常化，HBeAg血清清除率和HBsAg血清清除率均显着增加，到第10年分别达到96％，79％，38％和3.7％。 HBsAg水平相对于基线的平均下降为-0.08 log IU / mL /年。多变量分析确定HBsAg水平和基因型（A）是HBsAg血清清除的独立预测因子。 16名患者经历了病毒突破。通过Kaplan-Meier检验分析的病毒突破患者的累积百分比分别在第5年和第10年分别为1.5％和2.5％。治疗期间没有严重的不良事件。
结论

长期恩替卡韦治疗核仁（t）ide类似初始CHB患者与10年来优异的病毒反应和恩替卡韦耐药突变率低有关。基线HBsAg水平和基因型是恩替卡韦治疗期间HBsAg血清清除的预测因子。
关键词
乙型肝炎病毒恩替卡韦HBsAg血清清除抗性病毒突破