HBeAg水平在第24周预测HBeAg阳性慢性乙型肝炎患者8岁替诺福韦

StephenW

Aliment Pharmacol Ther. 2017 Oct 11. doi: 10.1111/apt.14362. [Epub ahead of print]
HBeAg levels at week 24 predict response to 8 years of tenofovir in HBeAg-positive chronic hepatitis B patients.
Wong D1,2, Littlejohn M1, Yuen L1, Jackson K1, Mason H1, Bayliss J1, Rosenberg G1, Gaggar A3, Kitrinos K3, Subramanian M3, Marcellin P4, Buti M5, Janssen HLA6, Gane E7, Locarnini S1, Thompson A2, Revill PA1.
Author information

1
    Division of Research and Molecular Development, Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Victoria, Australia.
2
    Department of Gastroenterology, St. Vincent's Hospital, Melbourne, Vic., Australia.
3
    Gilead Sciences, Foster City, CA, USA.
4
    Hôpital Beaujon, University of Paris, Clichy, France.
5
    Liver Unit, Vall d'Hebron (Ciberehd) University Hospital, Barcelona, Spain.
6
    Toronto Center for Liver Diseases, Toronto Western and General Hospital, University Health Network, University of Toronto, Toronto, ON, Canada.
7
    New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland, New Zealand.

Abstract
BACKGROUND:

Hepatitis B e antigen (HBeAg) seroconversion is a treatment endpoint for HBeAg-positive CHB, and a necessary precursor to HBsAg loss. Biomarkers that predict serological outcomes would be useful.
AIM:

To evaluate the utility of measuring HBeAg levels for predicting HBeAg seroconversion and HBsAg loss under long-term tenofovir (TDF) therapy.
METHODS:

A total of 266 patients were enrolled into a phase III study of TDF vs adefovir (ADV) for 48 weeks in HBeAg-positive patients, followed by open-label TDF up to 384 weeks. Serum HBeAg levels were measured for subjects with samples available at both baseline and week 24 of treatment (n = 200). Analysis compared subjects who achieved HBeAg seroconversion by week 384 vs no HBeAg seroconversion.
RESULTS:

HBeAg seroconversion rate was 52% by week 384. Time to HBeAg seroconversion was 80 weeks (IQR: 36-162). HBeAg decline at week 24 was associated with HBeAg seroconversion (1.63 vs 0.90 log10 PEIU/mL, P = .002). The optimal threshold for identifying HBeAg seroconversion was HBeAg decline ≥2.2 log10 PEIU/mL at week 24, with HBeAg seroconversion achieved by 76% of patients, compared to 44% if HBeAg decline <2.2 log10 (P < .0001). HBeAg decline ≥2.2 log10 PEIU/mL at week 24 was associated with HBsAg loss in genotype A or D patients (38% vs 15%, P = .03). Precore/basal core promotor variants were associated with lower baseline HBeAg levels, but not HBeAg seroconversion.
CONCLUSION:

Decline in HBeAg levels by week 24 was associated with HBeAg seroconversion and HBsAg loss in HBeAg-positive chronic hepatitis B patients treated with long-term TDF.

© 2017 John Wiley & Sons Ltd.

PMID:
    29023803
DOI:
    10.1111/apt.14362

StephenW

化学药理学2017年10月11日。doi：10.1111 / apt.14362。 [提前印刷]
HBeAg水平在第24周预测HBeAg阳性慢性乙型肝炎患者8岁替诺福韦的反应。
Wong D1,2，Littlejohn M1，Yuen L1，Jackson K1，Mason H1，Bayliss J1，Rosenberg G1，Gaggar A3，Kitrinos K3，Subramanian M3，Marcellin P4，Buti M5，Janssen HLA6，Gane E7，Locarnini S1，Thompson A2， Revill PA1。
作者信息

1
    澳大利亚维多利亚州彼得·多赫蒂感染与免疫研究所维多利亚州传染病参考实验室，墨尔本皇家医院研究与分子开发司。
2
    澳大利亚维多利亚州墨尔本圣文森特医院消化内科。
3
    美国加州福斯特市吉利德科学研究所。
4
    法国Clichy巴黎大学HôpitalBeaujon。
五
    肝脏单位，Vall d'Hebron（Ciberehd）大学医院，西班牙巴塞罗那。
6
    多伦多多伦多肝脏疾病中心多伦多西部和综合医院，大学健康网络，多伦多大学，多伦多，加拿大。
7
    新西兰肝移植单位，奥克兰市医院，新西兰奥克兰。

抽象
背景：

乙型肝炎e抗原（HBeAg）血清学转换是HBeAg阳性CHB的治疗终点，是HBsAg损失的必要前体。预测血清学结果的生物标志物将是有用的。
目标：

评估测量HBeAg水平用于预测长期替诺福韦（TDF）治疗中HBeAg血清学转换和HBsAg损失的效用。
方法：

在HBeAg阳性患者中，共有266名患者参与TDF对阿德福韦（ADV）的第三阶段研究，持续48周，其次为384周的开放标签TDF。在治疗基线和第24周（n = 200）的患者中测量血清HBeAg水平。分析比较了在384周时达到HBeAg血清学转换的患者与无HBeAg血清学转换的受试者。
结果：

HBeAg血清学转换率在第384周达到52％。HBeAg血清学转换的时间为80周（IQR：36-162）。 HBeAg在第24周下降与HBeAg血清学转换有关（1.63 vs 0.90 log10 PEIU / mL，P = .002）。鉴定HBeAg血清学转换的最佳阈值为24周时HBeAg降低≥2.2log10PEIU / mL，HBeAg血清学转换达到76％，而HBeAg降低<2.2 log10（P <0.0001）则为44％。 HBeAg下降≥2.2log10第24周时，PEIU / mL与A，D组患者HBsAg水平相关（38％vs 15％，P = 0.03）。 Precore /基础核心启动子变体与较低的基线HBeAg水平相关，但不与HBeAg血清学转换相关。
结论：

HBeAg水平在第24周下降与HBeAg血清学转换和HBsAg阳性慢性乙型肝炎患者长期TDF治疗中HBsAg的降低有关。

©2017 John Wiley＆Sons Ltd.

结论：
    29023803
DOI：
    10.1111 / apt.14362