12周的抗病毒治疗后肝内cccDNA的下降与增加免疫细胞的活性均

StephenW

Decline in intrahepatic cccDNA and increase in immune cell reactivity after 12 weeks of antiviral treatment were associated with HBeAg loss
Authors

    Q. Zheng,
    Y. Y. Zhu,
    J. Chen,
    Y. R. Liu,
    J. You,
    J. Dong,
    D. W. Zeng,
    L. Y. Gao,
    L. H. Chen,
    J. J. Jiang

    First published: 1 June 2014Full publication history
    DOI: 10.1111/jvh.12261
    Citing literature
    Article has an altmetric score of 1

Summary

Viral load reduction facilitates recovery of antiviral T-cell responses. Dynamic alterations in intrahepatic viraemia clearance and immune cell reactivity during the early phase of nucleoside analogue (NA) therapy and the impact of these changes on HBeAg seroconversion are unknown. Fifteen HBeAg-positive chronic hepatitis B (CHB) patients were treated with adefovir dipivoxil. T-cell reactivity to HBV core and surface antigens were tested using ELISPOT assay from baseline to week 48 post-treatment (at 4-week intervals). Before and at week 12 of treatment, paired liver biopsies were analysed for intrahepatic HBV-DNA and cccDNA via real-time fluorescent PCR. In situ detection of CD4+, CD8+ T cells and NK cells was analysed by immunohistochemistry. With viral load reduction, HBV-specific IFN-γ-producing CD4+ T cells in patients with HBeAg loss were greatly enhanced and reached the highest level at week 12, with further increase observed between week 36 and week 48. After 12 weeks of treatment, total intrahepatic HBV-DNA and cccDNA had significantly decreased; however, there was no difference in the viral loads or extent of reduction between patients with and without HBeAg loss. Paralleling reduction in viral load, intrahepatic CD8+T lymphocytes increased in patients with HBeAg loss compared with baseline values. Only one patient without HBeAg loss exhibited similar results. Increased immune cells were observed in certain patients along with reduced hepatic viral loads during the second phase of HBV-DNA decline, which could promote the recovery of antiviral immunity and facilitate HBeAg loss.

咬牙硬挺

国内作者发表的，可信度低

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Author Information

• 1Center of Liver Diseases, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
  
• 2Fujian Medical University, Fuzhou, Fujian, China
  
  

*  Correspondence: Dr. Jia-ji Jiang, Center of Liver Diseases, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350004, China.
E-mail: [email protected]

StephenW

关键词：

    抗病毒治疗;
    慢性乙型肝炎;
    HBeAg消失;
    T细胞反应性
    病毒下降

摘要

病毒载量的减少促进了抗病毒的T细胞应答的恢复。在核苷类似物（NA）治疗的早期阶段，在HBeAg血清学转换这些变化的影响，动态改变肝内病毒血症清除和免疫细胞的活性是未知的。十五HBeAg阳性慢性乙型肝炎（CHB）患者接受阿德福韦酯。 T细胞反应性的HBV核心和表面抗原是用ELISPOT测定从基线至第48周后处理（在4周的时间间隔）进行测试。前和周治疗的12，配对肝活检肝内HBV-DNA和cccDNA的通过实时荧光PCR检测。原位检测的CD4 +的，CD8 + T细胞和NK细胞通过免疫组织化学进行分析。与病毒载量下降，HBV特异性IFN-γ的CD4+ T细胞的患者HBeAg的损失被大大提高，并达到了在第12周的最高水平，每周4812周后治疗的第36周之间，以进一步增加观察肝内总HBV-DNA和cccDNA的有显著下降;然而，有患者和无HBeAg消失之间减少了病毒载量没有差别或程度。并联减少病毒载量，肝内CD8 + T淋巴细胞的患者与基线值相比，增加的HBeAg损失。只有一个病人无HBeAg转阴表现出类似的结果。中的HBV-DNA下降的第二阶段，这可能促进抗病毒免疫的恢复和促进HBeAg的损失增加的免疫细胞中观察到某些患者连同降低的肝脏病毒负荷。

StephenW

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我觉得这种类型的研究
很有意义: "病毒载量的减少促进了抗病毒的T细胞应答的恢复"
"在损失HBeAg的患者, HBV特异性IFN-γ的CD4+ T细胞被大大提高，并达到了在第12周的最高水平.以进一步增加48周36周之间.肝内总HBV-DNA和cccDNA的已显著下降".