长期的B型肝炎表面抗原（HBsAg）在核苷/核苷酸类似物治疗动

StephenW

Long-term hepatitis B surface antigen (HBsAg) kinetics during nucleoside/nucleotide analogue therapy: Finite treatment duration unlikely

    Stéphane Chevaliez1, 2, Corresponding author contact information, E-mail the corresponding author,
    Christophe Hézode2, 3,
    Stéphane Bahrami4,
    Marion Grare1,
    Jean-Michel Pawlotsky1, 2

    1 National Reference Center for Viral Hepatitis B, C and Delta, Department of Virology, Hôpital Henri Mondor, Université Paris-Est, Créteil, France
    2 INSERM U955, Créteil, France
    3 Department of Hepatology and Gastroenterology, Hôpital Henri Mondor, Université Paris-Est, Créteil, France
    4 Paris Health Economics and Health Services Research Unit, LIC EA 4393, Hôpital Henri Mondor, Université Paris-Est, Créteil, France

    http://dx.doi.org/10.1016/j.jhep.2012.11.039, How to Cite or Link Using DOI

Background & Aims

Information regarding long-term HBsAg kinetics during treatment with nucleoside/nucleotide analogues is limited. The aim of the present study was to assess whether finite nucleoside/nucleotide analogue treatment duration could be envisaged during the patient’s lifetime.
Methods

Patients with chronic hepatitis B receiving different schedules of nucleoside/nucleotide analogues were followed for a median duration of 102 months, i.e., 8.5 years (interquartile range: 88–119 months). Long-term HBV DNA and HBsAg level kinetics were modeled in order to estimate time to clear HBsAg during therapy in patients with undetectable HBV DNA.
Results

Antiviral therapy was associated with a slow but consistent reduction in the level of HBsAg in most of the patients. Three patterns of HBsAg level declines were identified: decline during both the detectable and undetectable HBV DNA phases; decline during the HBV DNA detectable period only; decline during the HBV DNA undetectable period only. The mean HBsAg titer at the time when HBV DNA became undetectable was 3.29 ± 0.49 Log10 international units (IU)/ml, and the mean slope was −0.007 ± 0.007 Log10 IU/month, i.e., an average decline of 0.084 Log10 IU/year. The corresponding calculated median number of years needed to clear HBsAg was 52.2 years (interquartile range: 30.8–142.7).
Conclusions

This study, based on the very long-term follow-up of patients with chronic hepatitis B treated with potent nucleoside/nucleotide analogues, shows that HBsAg clearance is unlikely to occur during the patient’s lifetime, even if HBV replication is well controlled. Thus, lifetime therapy is required in the vast majority of HBV-infected patients.

StephenW

背景与目的

关于长期HBsAg的动力学与核苷/核苷酸类似物在治疗过程中是有限的。本研究的目的是评估有限核苷/核苷酸类似物治疗时间是否可以设想在病人的一生。
方法

慢性乙型肝炎患者接受核苷/核苷酸类似物不同的时间表，随访时间中位数为102个月，即8.5年（四分位范围：88-119个月）。长期HBV DNA和HBsAg水平的动力学进行了建模，以便估计时间，以清除在不到HBV DNA的患者在治疗过程中的HBsAg。
结果

一个缓慢的，但一致的减少在大多数患者中HBsAg的水平与抗病毒治疗。三种模式的HBsAg水平下降，下降过程中的检测和检测不到HBV DNA阶段;下降过程中的HBV DNA检测期间，在HBV DNA检测不到的时间只下降。时成为检测不到HBV DNA的平均表面抗原滴度为3.29±0.49 log10的国际单位（IU）/毫升，平均斜率为-0.007±0.007 LOG10 IU /月，也就是说，平均跌幅为0.084 LOG10 IU /年。年需要清除乙肝表面抗原相应的计算中位数为52.2岁（四分位范围：30.8-142.7）。
结论

很长的长期​​随访的患者治疗慢性乙型肝炎的核苷/核苷酸类似物具有强大的基础上，本研究显示，HBsAg清除是不可能发生在患者的生存期，即使HBV复制得到很好的控制。因此，需要终身治疗的HBV感染者中的绝大多数。

鱿鱼

看来核苷（酸）长期 使用的结局也不乐观哈

StephenW

回复 鱿鱼 的帖子

我同意你的观察.因此，除了保持病毒载量非常低,我们需要额外的治疗方法.


有两种方法可以减少在肝脏中的cccDNA的数量:
1. 当受感染的肝细胞自然分裂,一些的cccDNA将丢失.
即使血清HBV DNA是非常低或测不到, 少量新的病毒颗粒仍在生产，能感染邻居细胞和补充cccDNA的池. 因此，我们必须找到一种方法来阻止感染. Mycrludex是正在测试一种新的药物 - 它可以防止乙肝病毒进入肝细胞.目前已知NTCP是HBV进入的受体, 科学家发现了另外两个现有已FDA批准的抑制NTCP的药物 - Ezetimibe 和 Irbesartan.

2. HBV特异性T细胞，杀死被感染的肝细胞.
一些科学家认为，如果我们能降低血清HBsAg数量，乙肝病毒特异性T细胞将被激活. 干扰素和REP9AC可以降低血清HBsAg数量. ARC520亦可能.


因此，治愈可能依赖于结合 替诺福韦/恩替卡韦，干扰素，REP9AC，Mycrludex, Ezetimibe 和 Irbesartan.

styxl

鱿鱼

回复 StephenW 的帖子

谢谢，期待更好的疗法和药物能尽快应用于临床。

咬牙硬挺

顽固不化的病毒，我恨死你了

MP4

厄贝沙坦