替诺治疗HBeAg阳性患者乙肝表面抗原损失的动力学

StephenW

Research Article
Kinetics of hepatitis B surface antigen loss in patients with HBeAg-positive chronic hepatitis B treated with tenofovir disoproxil fumarate

    Patrick Marcellin 1, , ,
    Maria Buti 2,
    Zahari Krastev 3,
    Robert A. de Man 4,
    Stefan Zeuzem 5,
    Lillian Lou 6,
    Anuj Gaggar 6,
    John F. Flaherty 6,
    Benedetta Massetto 6,
    Lanjia Lin 6,
    Phillip Dinh 6,
    G. Mani Subramanian 6,
    John G. McHutchison 6,
    Robert Flisiak 7,
    Selim Gurel 8,
    Geoffrey M. Dusheiko 9,
    E. Jenny Heathcote 10

doi:10.1016/j.jhep.2014.07.019

Background & Aims

In a study of 266 chronic hepatitis B e antigen (HBeAg)-positive patients, 23 experienced hepatitis B surface antigen (HBsAg) loss with up to 5 years of tenofovir disoproxil fumarate (TDF) treatment. HBsAg kinetics in patients with and without HBsAg loss and predictors of HBsAg loss were evaluated.

Methods

HBsAg levels were quantified every 12 weeks. A multivariable regression analysis, involving prespecified baseline characteristics and on-treatment response parameters, was performed; a stepwise procedure identified independent predictors of HBsAg loss.

Results

Among patients with HBsAg loss, 14 (61%), 1 (4%), 0 and 7 (30%) were genotypes A through D, respectively; 1 (4%) was genotype F. HBsAg loss was preceded by viral suppression (HBV DNA <29 IU/ml; n = 23) and HBeAg loss (n = 19). Among treated patients the strongest independent predictors of HBsAg loss were Caucasian race with genotype A/D and ⩽4 years of infection (HR = 14.3, 95% confidence interval [CI] 4.7–43.4; p <0.0001) and an HBsAg decline of ⩾1 log10 IU/ml at week 24 (HR = 13.7, 95% CI 5.6–33.7; p <0.0001). Among TDF-treated patients, a reduction in HBsAg level of ⩾1-log10 by week 12 or 24 had a positive predictive value of 35%–45%, respectively, and a negative predictive value of 94%–97%, respectively.

Conclusions

HBsAg loss in HBeAg-positive patients receiving TDF involves a chronology of virologic and serologic responses; patients with HBV genotypes A or D and a rapid early decline in HBsAg are more likely to lose HBsAg.
Abbreviations

    CHB, chronic hepatitis B;
    HBsAg, hepatitis B surface antigen;
    HBeAg, hepatitis B e antigen;
    TDF, tenofovir disoproxil fumarate;
    HBV, hepatitis B virus;
    KM, Kaplan-Meier;
    EIA, enzyme immunoassay;
    CI, confidence interval;
    ALT, alanine aminotransferase;
    NPV, negative predictive value;
    PPV, positive predictive value

Keywords

    Chronic hepatitis B;
    Hepatitis B surface antigen;
    Tenofovir disoproxil fumarate

    Corresponding author. Address: Service d’Hépatologie, Hôpital Beaujon, 100 Boulevard du General Leclerc, 92110 Clichy, France. Tel.: +33 (0) 1 40 87 53 38; fax: +33 (0) 1 41 40 87 53 39.

StephenW

研究论文
乙肝表面抗原损失的患者动力学与富马酸替诺福韦酯治疗HBeAg阳性慢性乙型肝炎

    帕特里克Marcellin1，，，
    玛丽亚·布提2，
    Zahari Krastev3，
    罗伯特·德·曼4，
    斯特凡Zeuzem5，
    莉莲楼6，
    Anuj Gaggar6，
    约翰·弗莱厄蒂6，
    Benedetta酒店马赛托6，
    兰家林6，
    菲利普亭6，
    G.玛尼萨勃拉曼尼亚6，
    约翰·G·McHutchison6，
    罗伯特Flisiak7，
    塞利姆居雷尔8，
    杰弗里·M·Dusheiko9，
    E.珍妮希思科特10

DOI：10.1016/ j.jhep.2014.07.019

背景与目的

在266慢性乙型肝炎e抗原（HBeAg）阳性的患者中，23有经验的B型肝炎表面抗原（HBsAg），损失达5年的富马酸替诺福韦酯（TDF）治疗的研究。乙肝表面抗原动力学的患者和无HBsAg消失和HBsAg消失的预测进行了评估。

Methods

HBsAg水平进行定量，每12周。多变量回归分析，涉及到预先确定的基线特征和对治疗的反应参数，进行;一个逐步的过程确定HBsAg消失的独立预测因素。

结果

其中患者的HBsAg消失，14（61％），1（4％），0和7（30％）是基因型A到D，分别为; 1（4％）的基因型F. HBsAg消失之前有抑制病毒（HBV DNA<29 IU/毫升; N=23）和HBeAg消失（N=19）。其中治疗的患者HBsAg消失的最强的独立预测因子是高加索人种基因型A / D和⩽4年感染（HR=14.3，95％可信区间[CI]4.7-43.4; P <0.0001）和乙肝表面抗原的下降⩾ 1日志10 IU/ ml的第24周（HR=13.7，95％CI为5.6-33.7; P <0.0001）。之间的TDF治疗的患者，在⩾1-log10的HBsAg的水平降低了12周或24具有35％分别-45％，分别为一个阳性预测值，和94％-97％，阴性预测值。

结论

HBsAg消失在接受TDF HBeAg阳性患者涉及的病毒学和血清学应答的年代;患者HBV基因型A或D和乙肝表面抗原快速年初下降更可能失去乙肝表面抗原。
缩略语

    慢性乙型肝炎，慢性乙型肝炎;
    乙肝表面抗原，乙肝表面抗原;
    大三阳，乙肝e抗原;
    TDF，富马酸替诺福韦酯;
    乙肝病毒，乙型肝炎病毒;
    KM，Kaplan-Meier法;
    EIA酶免疫分析;
    CI，置信区间;
    ALT，丙氨酸氨基转移酶;
    净现值（NPV），阴性预测值;
    PPV，阳性预测值

关键字

    慢性乙型肝炎;
    乙型肝炎表面抗原;
    富马酸替诺福韦酯

    Corresponding author。地址：服务D'Hépatologie，HOPITAL Beaujon，100大道杜勒克莱尔将军，92110克利希，法国。电话：+33（0）140875338;传真：+33（0）14140875339。