病毒感染的参数不核苷类似物本身相关，在治疗慢性乙型肝

StephenW

Source: World J Gastroenterol  |  Posted 3 weeks ago
Viral infection parameters not nucleoside analogue itself correlates with host immunity in nucleoside analogue therapy for chronic hepatitis B; Li C, Hu J, Xue J, Yin W, Liu Y, Fan W, Xu H, Liang X; World Journal of Gastroenterology 20 (28), 9486-96 (Jul 2014)

  

AIM To determine the relationship between host immunity and the characteristics of viral infection or nucleoside analogues (NAs) themselves in patients with chronic hepatitis B (CHB) receiving NA therapy.

METHODS Fifty-two hepatitis B envelope antigen (HBeAg) positive CHB patients were enrolled and divided equally into two groups. One group received telbivudine (LDT, 600 mg/d), and the other group received lamivudine (LAM, 100 mg/d). Clinical, virological and immunological parameters were assessed at the baseline and at 4, 12, 24, 36 and 48 wk.

RESULTS Both groups achieved significant hepatitis B virus (HBV) replication inhibition and alanine aminotransferase normalization at 48 wk. At the baseline, compared to healthy controls, CHB patients had a lower circulating CD8 T cell frequency (29.44% ± 11.55% vs 37.17% ± 7.30%, P = 0.03) and higher frequencies of programmed death 1 positive CD8 T cells (PD-1+ CD8 T) (16.48% ± 10.82% vs 7.02% ± 3.62%, P = 0.0001) and CD4+ CD25+ FoxP3+ T regulatory cells (Tregs) (23.64% ± 9.38% vs 13.60% ± 6.06%, P = 0.001). On therapy, at the beginning 24 wk with the levels of hepatitis B virus deoxyribonucleic acid (HBV DNA) and HBeAg declining, the frequencies of PD-1+ CD8 T cells and Treg cells gradually and significantly declined at 12 and 24 wk in both therapy groups. At treatment week 4, patients treated with LDT had a lower frequency of PD-1+ CD8 T cells compared to patients treated with LAM (10.08% ± 6.83% vs 20.51% ± 20.96%, P = 0.02). The frequency of PD-1+ CD8 T cells in all of the CHB patients was significantly correlated with both the HBV DNA level (r = 0.45, P = 0.01) and HBeAg level (r = 0.47, P = 0.01) at treatment week 24, but the frequency of Treg cells was only significantly correlated with the HBeAg level (r = 0.44,P = 0.02). Furthermore, the ability of CD8 T cells to secrete pro-inflammatory cytokines was partially restored after 24 wk of therapy.

CONCLUSION NA-mediated HBV suppression could down-regulate the production of negative regulators of host immunity during the first 24 wk of therapy and could partially restore the ability of CD8 T cells to secrete pro-inflammatory cytokines. This immune modulating response may be correlated with the levels of both HBV DNA and HBeAg.

StephenW

资料来源：世界胃肠病学杂志|发表于3天前
病毒感染的参数不核苷类似物本身相关，在治疗慢性乙型肝炎的核苷类似物治疗宿主的免疫力;李C，胡Ĵ，薛Ĵ，殷瓦，刘毅，樊W，徐H，梁X;消化内科20世界日报（28），9486-96（2014年7月）

  

旨在决定因子宿主免疫和病毒感染或核苷类似物（NAS）自己在慢性乙型肝炎（CHB）接受NA治疗的特性之间的关系。

方法52乙型肝炎包膜抗原（HBeAg）阳性CHB及入选患者随机分为两组。一组接受替比夫定（LDT，600毫克/天），而另一组接受拉米夫定（LAM100毫克/天）。临床，病毒学和免疫学指标进行评估的基线和4，12，24，36和48周。

结果两组在48周实现显著乙型肝炎病毒（HBV）复制的抑制和谷丙转氨酶正常化。在基线，健康对照组相比，慢性乙肝患者有较低的循环CD8 T细胞的频率（11：55％比29.44％±37.17％±7.30％，P=0.03）和程序性死亡1例阳性CD8 + T细胞的频率较高（PD-1+ CD8 + T）（16：48％±10.82％和07.02％±3.62％，P = 0.0001）和CD4+ CD25 +的FoxP3+调节性T细胞（Treg细胞）（23.64％±9：38％比13.60％±6.6％，P = 0.001）。关于治疗，在开始24周与乙型肝炎病毒脱氧核糖核酸（HBV-DNA）和HBeAg的水平下降，PD-1的CD8 + T细胞和Treg细胞显着逐渐下降，在12和24周的在两种治疗的频率组。在治疗第4周，与LDT治疗的患者PD-1+ CD8 + T细胞的较低频率相较于林治疗的患者（10.08％±6.83％和20.96％±20：51％，P=0.02）。 PD-1 + CD8 + T细胞中的所有CHB患者的频率两者的HBV DNA水平相关（r =0.45，P = 0.01）和HBeAg水平相关（r =0.47，P = 0.01）在治疗24周的相关性显着但调节性T细胞的频率只显着正相关与e抗原水平相关（r=0.44，P=0.02）。另外，CD8 + T细胞分泌促炎性细胞因子的能力，24周的治疗后，被部分还原。

结论NA-介导的HBV抑制能下调生产宿主免疫的负调节物的过程中的第一个24的治疗周并能部分恢复CD8T细胞分泌促炎性细胞因子的能力。此调节免疫应答可能与的两种HBV DNA和HBeAg的水平。