恩替卡韦与晚期病毒复发相关而不是替诺福韦

StephenW

August 06, 2018
Entecavir Associated With Later Virological Relapse Than Tenofovir

The type of antiviral agent, entecavir vs tenofovir, was significantly associated with the timing of virological relapse.

A comparison of the nucleos(t)ide analogues tenofovir and entecavir revealed that virological relapse occurred much later for people with a chronic hepatitis B virus (HBV) infection who were e antigen negative after stopping entecavir, according to findings published in The Journal of Infectious Diseases.

A total of 220 people aged 18 to 65 years were enrolled from the Asian-Pacific region; participants represented 38 centers across 7 countries. Each participant received treatment with nucleos(t)ide analogues for at least 2 years. All participants had a chronic HBV infection, were e antigen negative, and had been producing hepatitis B e antibodies for at least 1 year before study screening. The participants were divided into groups: those taking entecavir (n=154) and those taking tenofovir disoproxil (n=66).

Therapy with each nucleos(t)ide analogue was stopped after 24 weeks. “Follow-up was until 24 weeks or [nucleos(t)ide analogue] retreatment.” During the first 8 weeks, participants were followed every 2 weeks. After the 8-week mark, participants were followed every 4 weeks. Investigators noted the major end point of the study was “virological remission (HBV-DNA levels <40 IU/mL) until 24 weeks after stopping [nucleos(t)ide analogues].”

Virological relapse (HBV DNA > 2,000 IU/mL) occurred in 24.5% of the participants (n=54) until week 12 and 57.3% (n=126) until week 24. Some participants (32.7%; n=72) experienced a later relapse between week 16 and week 24. Of the participants treated with tenofovir, 71% (n=47) had virological relapse until week 12. Of those treated with entecavir, 4.5% had virological relapse (n=7) in the same period (P<.0001). Researchers found that 6 weeks after ceasing tenofovir marked the median time to virological relapse; 24 weeks was the median time for relapse after discontinuing entecavir (P< .0001).

Study limitations include a homogenous pool of participants. Researchers also note that there were no assessments for nucleos(t)ide analogue resistance in the study, nor was virological relapse “confirmed immediately by a repeated test.”

According to study authors, “this is the largest prospective study showing that the type of nucleos(t)ide analogue affects relapse after cessation of therapy. This is an important finding for clinical practice as well as for future studies addressing whether treatment discontinuation has an impact on functional cure of HBV infection.” The investigators also note that given the study findings, there may be more to the choice of nucleos(t)ide analogues than “lamivudine resistance, costs, or certain comorbidities.” They recommended “close follow-up even more than 3 months after treatment discontinuation” for people treated with entecavir.


This study was supported by ABIVAX, a biotechnology company in Paris, France. Please refer to the reference for a complete list of authors' disclosures.
Reference

Höner zu Siederdissen C, Hui AJ, Sukeepaisarnjaroen W, et al. Contrasting timing of virological relapse after discontinuation of tenofovir or entecavir in hepatitis B e antigen-negative patients [published online June 9, 2018]. J Infect Dis. doi:10.1093/infdis/jiy350

StephenW

2018年8月6日
恩替卡韦与晚期病毒复发相关而不是替诺福韦

抗病毒药物恩替卡韦与替诺福韦的类型与病毒学复发的时间显着相关。

核苷（t）ide类似物替诺福韦和恩替卡韦的比较显示，对于患有慢性乙型肝炎病毒（HBV）感染的人，在停用恩替卡韦后e抗原阴性的病毒复发发生得更晚，根据发表在“传染病杂志”上的研究结果疾病。

共有220名18至65岁的人从亚太地区入学;参与者代表了7个国家的38个中心。每位参与者接受核苷（t）ide类似物治疗至少2年。所有参与者均有慢性HBV感染，e抗原阴性，并且在研究筛选前至少生产乙型肝炎e抗体至少1年。参与者分为几组：服用恩替卡韦（n = 154）和服用替诺福韦地索普西（n = 66）的患者。

24周后停止使用每种核苷（t）ide类似物的治疗。 “随访直到24周或[核苷（酸）类似物]再治疗。”在前8周，每2周跟踪一次。在8周后，每4周跟踪一次参与者。研究人员指出，该研究的主要终点是“病毒学缓解（HBV-DNA水平<40 IU / mL），直至停止[核苷（酸）类似物]后24周。”

病毒学复发（HBV DNA> 2,000 IU / mL）发生在24.5％的参与者（n = 54）直到第12周和57.3％（n = 126）直到第24周。一些参与者（32.7％; n = 72）经历过在第16周和第24周之间复发。在使用替诺福韦治疗的参与者中，71％（n = 47）病毒学复发直至第12周。在恩替卡韦治疗的患者中，4.5％在同一时期有病毒学复发（n = 7） （P <0.0001）。研究人员发现停用替诺福韦后6周标志着病毒学复发的中位时间; 24周是停用恩替卡韦后复发的中位时间（P <.0001）。

研究限制包括同质的参与者群。研究人员还指出，研究中没有对核苷（酸）类似物抗性的评估，病毒学复发也没有“通过重复试验立即证实”。

研究作者表示，“这是最大的前瞻性研究，显示核苷（t）类似物的类型会影响停止治疗后的复发。这是临床实践以及未来研究的一个重要发现，旨在解决治疗中断对HBV感染功能性治愈的影响。“研究者还注意到，根据研究结果，核的选择可能更多（t ）“拉米夫定耐药性，费用或某些合并症”的类似物。对于接受恩替卡韦治疗的患者，他们建议“治疗中止后3个月内密切随访”。


这项研究得到了法国巴黎生物技术公司ABIVAX的支持。有关作者披露的完整列表，请参阅参考资料。
参考

HönerzuSiederdissen C，Hui AJ，Sukeepaisarnjaroen W，et al。对比乙型肝炎e抗原阴性患者停用替诺福韦或恩替卡韦后病毒学复发的时间[2018年6月9日在线发表]。 J Infect Dis。 DOI：10.1093 / infdis / jiy350