反应迟缓治疗初治乙肝患者恩替卡韦治疗是通过免疫反应而

StephenW

Slow response to entecavir treatment in treatment-naive HBV patients is conditioned by immune response rather than by the presence or selection of refractory variants.
Solmone M, Giombini E, Vincenti D, Rozera G, Testa A, Moscetti A, Catalano M, Abbate I, Capobianchi MR, Menzo S.
Author information

    National Institute for Infectious Diseases 'Lazzaro Spallanzani' I.R.C.C.S., Laboratory of Virology, Roma, Italy.

Abstract
BACKGROUND:

Entecavir is the drug of choice as first line treatment for naïve HBV patients. Thanks to the high genetic barrier to resistance, treatment failure remains rare, but occurs within 3 years of initiation, suggesting that viral genetic characteristics may provide a fast lane to resistance. One of the main concerns is the long time to viral suppression observed in some (even naïve) patients. The reasons for this phenomenon were investigated in a group of chronic hepatitis B naive patients.
METHODS:

Out of 23 naïve patients starting treatment, the 5 with the best and those with the worst viral load decay curves were selected for the study. Quasispecies analysis was performed for the RT/HBsAg ORF by Ultra-Deep PyroSequencing. For each patient, the analysis was performed at baseline (T0) and when viremia reached between1000 and 200 IU/ml (T1).
RESULTS:

The few resistance mutations present at T0 were not selected by treatment: no other resistance mutations nor suggestive mutational patterns were selected at T1. Selective pressure analysis indicated that both at T0 and T1 the HBsAg ORF was subjected to a significantly higher pressure in rapid responders, especially in a region rich in CTL epitopes.
CONCLUSIONS:

The results did not provide evidence that a slower response to entecavir is due to the emergence of less sensitive variants. Rather, the lower selective pressure and variability in humoral and CTL epitopes in slow responders suggests that their immune response might be at odds in rapidly clearing infected cells from the liver.

StephenW

反应迟缓治疗初治乙肝患者恩替卡韦治疗是通过免疫反应而不是顽固变种存在或选择条件。
Solmone M， Giombini E，文森蒂D， Rozera G，特斯塔A， Moscetti A，卡塔兰诺M，阿巴特我， Capobianchi MR， Menzo S。
作者信息

    国立传染病“拉扎罗斯帕兰扎尼' IRCCS ，病毒学实验室，罗马，意大利。

摘要
背景：

恩替卡韦是首选药物作为第一线治疗乙肝初治患者。由于采用了高耐药基因屏障，治疗失败仍然罕见，但发生在3年内启动，这表明病毒的遗传特征可能会提供一个快速通道阻力。其中一个主要的担忧是很长一段时间，以抑制病毒在某些（甚至天真）患者中观察到。在这种现象的原因进行了调查，一组慢性乙肝初治患者中。
方法：

出23初治患者开始治疗时， 5最好和那些最坏的病毒载量衰减曲线被选作研究。由超深焦磷酸测序准种进行分析，对于RT / HBsAg的ORF 。对于每个患者，在基线（T0）进行分析，并当血症达到between1000和200国际单位/毫升（T1）。
结果：

少数耐药突变出现在T0未选中治疗：没有其他的耐药突变，也不暗示的突变模式在T1被选中。选择压力的分析表明，无论是在T0和T1的HBsAg ORF进行快速响应一个显著更高的压力，特别是在富含CTL表位的区域。
结论：

结果没有提供证据证明恩替卡韦响应速度变慢是由于不太敏感的变体的出现。相反，较低的选择压力和变化在缓慢的体液免疫应答和CTL表位表明他们的免疫反应可能是在赔率从肝脏迅速清除受感染的细胞。