HBeAg阴性慢性乙型肝炎患者外周血单个核细胞中恩替卡韦渗透

StephenW

Antivir Ther. 2017 Nov 23. doi: 10.3851/IMP3207. [Epub ahead of print]
Correlation between entecavir penetration in peripheral blood mononuclear cells and HBV DNA decay during treatment of HBeAg-negative chronic hepatitis B.De Nicolò A1, Boglione L1, Cusato J1, Fatiguso G1, Favata F1, Allegra S1, Cariti G1, Di Perri G1, D'Avolio A1.
Author information
1University of Turin, Department of Medical Sciences, 'Amedeo di Savoia' Hospital, Turin, Italy.

AbstractBACKGROUND: Recently, due to its high effectiveness and tolerability, the treatment of chronic hepatitis B with entecavir became a standard practice. However, limited knowledge is currently available about its pharmacokinetic behavior and intracellular disposition. Recently, our group reported an inverse correlation between entecavir plasma concentrations and the HBV DNA decay at the first and third month of treatment, respectively. ​: In this paper we investigated the disposition of entecavir in peripheral blood mononuclear cells (PBMC) and in plasma, in order to evaluate the relationship between intracellular penetration and response, in a cohort of naïve patients with HBeAg-negative CHB.
METHODS: Thirty-tree patients were prospectively enrolled and gave written informed consent: the monitoring of clinical parameters (e.g. HBV DNA, HBsAg, ALT, etc.) was carried out at the baseline and then monthly. Entecavir intra-PBMC and plasma trough concentrations were measured at 1 month of treatment, through a validated method based on liquid chromatography coupled with tandem mass spectrometry.
RESULTS: While plasma entacavir analysis confirmed previous evidence of inverse correlation between drug concentrations and HBV DNA decrease after 3 months of treatment (r=-0.723; p<0.001), this correlation was not significant for intra-PBMC concentrations. When the intracellular disposition ratio (intra-PBMC/plasma concentration ratio) was considered, it showed a direct and significant correlation with HBV DNA decay at the third month (r=0.485; p=0.004).
CONCLUSIONS: These results suggest that the antiviral activity of entacavir is dependent on its intracellular uptake, thus resulting in lower plasma concentrations in patients who have a marked HBV DNA decrease during treatment.


PMID:29168696DOI:10.3851/IMP3207

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StephenW

Antivir Ther。 2017年11月23日。doi：10.3851 / IMP3207。 [电子版提前打印]
HBeAg阴性慢性乙型肝炎患者外周血单个核细胞中恩替卡韦渗透与HBV DNA降解的相关性
DeNicolòA1，Boglione L1，Cusato J1，Fatiguso G1，Favata F1，Allegra S1，Cariti G1，Di Perri G1，D'Avolio A1。
作者信息

1
    都灵大学医学科学系，意大利都灵Amedeo di Savoia医院。

抽象
背景：

最近，由于其高效和耐受性，用恩替卡韦治疗慢性乙型肝炎成为一种标准的做法。然而，目前有限的知识是关于其药代动力学行为和细胞内处置。最近，我们小组报告恩替卡韦血浆浓度与治疗第一个月和第三个月的HBV DNA衰减分别呈负相关。 ：在本文中，我们调查了恩替卡韦在外周血单个核细胞（PBMC）和血浆中的配置，以评估细胞内渗透和反应之间的关系，在初次HBeAg阴性慢性乙型肝炎患者队列。
方法：

前瞻性纳入了30名患者，并给出了书面的知情同意书：在基线和每月一次的情况下监测临床参数（如HBV DNA，HBsAg，ALT等）。通过基于液相色谱联用串联质谱法的验证方法，在治疗1个月时测量恩替卡韦内PBMC和血浆谷浓度。
结果：

尽管血浆恩替卡韦分析证实了治疗3个月后药物浓度与HBV DNA降低之间存在负相关的先前证据（r = -0.723; p <0.001），但这种相关性对于PBMC内浓度并不显着。当考虑细胞内配置比例（PBMC /血浆浓度比）时，与第3个月的HBV DNA衰减直接和显着相关（r = 0.485; p = 0.004）。
结论：

这些结果表明，依那西韦的抗病毒活性依赖于其细胞内摄取，因此在治疗期间具有显着的HBV DNA降低的患者中导致较低的血浆浓度。

结论：
    29168696
DOI：
    10.3851 / IMP3207

Espoir

These results suggest that the antiviral activity of entecavir is dependent on its intracellular uptake,  thus resulting in lower plasma concentrations in patients who have a marked HBV DNA decrease during treatment.
——这些结果表明，恩替卡韦的抗病毒活性取决于其细胞内摄取，从而导致治疗期间HBV DNA显着降低的患者血浆浓度降低。
这可能是未发现的恩替卡韦另一个副作用