低乙型肝炎表面抗原和HBV DNA水平预测乙型肝炎e抗原阳性慢性

StephenW

Aliment Pharmacol Ther. 2019 Feb;49(4):448-456. doi: 10.1111/apt.15098.
Low hepatitis B surface antigen and HBV DNA levels predict response to the addition of pegylated interferon to entecavir in hepatitis B e antigen positive chronic hepatitis B.
Liem KS1,2, van Campenhout MJH2, Xie Q3, Brouwer WP2, Chi H2, Qi X4, Chen L4, Tabak F5, Hansen BE1,2,6, Janssen HLA1.
Author information

1
    Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
2
    Department of Gastroenterology and Hepatology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.
3
    Department of Infectious Diseases, Ruijin Hospital, Jiaotong University, Shanghai, China.
4
    Department of Hepatitis Disease, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
5
    Çerrahpasa Medical Faculty, Istanbul, Turkey.
6
    Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada.

Abstract
BACKGROUND:

Various treatment combinations of peginterferon (PEG-IFN) and nucleos(t)ide analogues have been evaluated for chronic hepatitis B (CHB), but the optimal regimen remains unclear.
AIMS:

To study whether PEG-IFN add-on increases response compared to entecavir (ETV) monotherapy, and whether the duration of ETV pretreatment influences response.
METHODS:

Response was evaluated in HBeAg positive patients previously treated in two randomized controlled trials. Patients received ETV pretreatment for at least 24 weeks and were then allocated to 24-48 weeks of ETV+PEG-IFN add-on, or continued ETV monotherapy. Response was defined as HBeAg loss combined with HBV DNA <200 IU/mL 48 weeks after discontinuing PEG-IFN.
RESULTS:

Of 234 patients, 118 were assigned PEG-IFN add-on and 116 continued ETV monotherapy. Response was observed in 38/118 (33%) patients treated with add-on therapy and in 23/116 (20%) with monotherapy (P = 0.03). The highest response to add-on therapy compared to monotherapy was observed in PEG-IFN naive patients with HBsAg levels below 4000 IU/mL and HBV DNA levels below 50 IU/mL at randomization (70% vs 34%; P = 0.01). Above the cut-off levels, response was low and not significantly different between treatment groups. Duration of ETV pretreatment was associated with HBsAg and HBV DNA levels (both P < 0.005), but not with response (P = 0.82).
CONCLUSIONS:

PEG-IFN add-on to ETV therapy was associated with higher response compared to ETV monotherapy in patients with HBeAg positive CHB. Response doubled in PEG-IFN naive patients with HBsAg below 4000 IU/mL and HBV DNA below 50 IU/mL, and therefore identifies them as the best candidates for PEG-IFN add-on (Identifiers: NCT00877760, NCT01532843).

©2019 The Authors. Alimentary Pharmacology & Therapeutics Published by John Wiley & Sons Ltd.

PMID:
    30689258
DOI:
    10.1111/apt.15098

StephenW

Aliment Pharmacol Ther。 2019年2月; 49（4）：448-456。 doi：10.1111 / apt.15098。
低乙型肝炎表面抗原和HBV DNA水平预测乙型肝炎e抗原阳性慢性乙型肝炎对聚乙二醇化干扰素加入恩替卡韦的反应。
Liem KS1,2，van Campenhout MJH2，Xie Q3，Brouwer WP2，Chi H2，Qi X4，Chen L4，Tabak F5，Hansen BE1,2,6，Janssen HLA1。
作者信息

1
    多伦多综合医院多伦多肝病中心，大学健康网络，多伦多，安大略省，加拿大。
2
    荷兰鹿特丹鹿特丹伊拉斯姆斯大学医学中心消化内科和肝病学系。
3
    上海交通大学瑞金医院感染科，上海
4
    复旦大学上海市公共卫生临床中心肝炎科，上海
五
    Çerrahpasa医学院，土耳其伊斯坦布尔。
6
    加拿大安大略省多伦多市多伦多大学卫生政策，管理和评估研究所。

抽象
背景：

聚乙二醇干扰素（PEG-IFN）和核苷（t）ide类似物的各种治疗组合已被评估用于慢性乙型肝炎（CHB），但最佳方案仍不清楚。
目的：

研究与恩替卡韦（ETV）单药治疗相比，PEG-IFN添加剂是否会增加反应，以及ETV预处理的持续时间是否会影响反应。
方法：

在先前在两项随机对照试验中治疗的HBeAg阳性患者中评估了反应。患者接受ETV预处理至少24周，然后分配到24-48周的ETV + PEG-IFN附加或继续ETV单一疗法。在停止PEG-IFN后48周，响应被定义为HBeAg消失与HBV DNA <200IU / mL相结合。
结果：

在234名患者中，118名被分配PEG-IFN附加和116名持续的ETV单一疗法。在38/118（33％）接受附加治疗的患者和23/116（20％）接受单药治疗的患者中观察到反应（P = 0.03）。在单次治疗中，与单药治疗相比，附加治疗的最高反应在HBsAg水平低于4000 IU / mL且HBV DNA水平低于50 IU / mL的随机化患者中观察到（70％vs 34％; P = 0.01）。高于临界水平，治疗组之间的反应较低且无显着差异。 ETV预处理的持续时间与HBsAg和HBV DNA水平相关（均P <0.005），但与反应无关（P = 0.82）。
结论：

与HBVAg阳性CHB患者的ETV单一疗法相比，ETV治疗的PEG-IFN添加与更高的反应相关。对于HBsAg低于4000 IU / mL且HBV DNA低于50 IU / mL的PEG-IFN初治患者，反应加倍，因此将其鉴定为PEG-IFN附加的最佳候选者（标识符：NCT00877760，NCT01532843）。

©2019作者。由John Wiley＆Sons Ltd.出版的消化药理学和治疗学

结论：
    30689258
DOI：
    10.1111 / apt.15098

StephenW

https://onlinelibrary.wiley.com/doi/full/10.1111/apt.15098