He J, Yao Y Q, Xia R X, Qiu T J, Long L, Wang Y, Jiang Y
Department of Infectious Diseases, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Zhonghua Gan Zang Bing Za Zhi. 2022 Mar 20;30(3):316-322. doi: 10.3760/cma.j.cn501113-20191223-00476.
To dynamically observe the clinical efficacy of entecavir and the changes of PD-1CXCR5CD4T lymphocytes and sPD-1 levels in peripheral blood of HBeAg-positive chronic hepatitis B virus carriers treated with entecavir, and further explore its clinical significance. There were 31 cases of chronic hepatitis B virus carriers in the treatment group (A), 32 cases of chronic hepatitis B virus carriers in the treatment group (B), and 15 cases of chronic hepatitis B virus carriers in the non-treatment group (C).Three groups peripheral blood samples and clinical data at 0, 24 and 48 weeks were collected and compared. PD-1CXCR5CD4T lymphocytes were detected by flow cytometry, and the level of sPD-1 was detected by enzyme-linked immunosorbent assay. ANOVA and Spearman correlation analysis were performed on the measurement data among the three groups. At week 0, the serum levels of HBsAg, HBeAg and HBV DNA were significantly higher in groups A and C than group B. PD-1CXCR5CD4T lymphocytes in peripheral blood were significantly higher in group B (4.70%±1.58%) than group A (3.25%±1.01%) and group C (2.77%±0.67%) (=16.65, <0.05). There was no significant difference between group A and group C (>0.05). Peripheral blood sPD-1 in group B [(1 866.62±1 472.70) pg/ml] was significantly higher than group A [(824.86±538.66) pg/ml] and group C [(618.19±602.62) pg/ml] (=10.95, <0.05). There was no significant difference between group A and group C (>0.05). At 48 weeks, the serum HBsAg did not decrease significantly in groups A and C than baseline (>0.05), but were significantly higher than group B (<0.05). Serum HBeAg levels were decreased significantly in groups A and B than baseline (<0.05). <0.05), but group A was significantly higher than group B (<0.05), and there was no significant difference between group A and group C (>0.05). Serum HBV DNA level was significantly lower in groups A and B than group C (<0.05), and there was no significant difference between group A and group B (>0.05). Peripheral blood PD-1CXCR5CD4T lymphocytes were significantly lower in Group A (1.56%±0.73%) and group B (1.32%±0.43%) than group C (2.64%±0.85%) (<0.05). Peripheral blood sPD-1 were significantly lower in group A [(289.05±215.86) pg/ml] and group B [(236.01±173.92) pg/ml] than group C [(650.34±598.46) pg/ml] (<0.05). There was no significant difference between group A and group B. Correlation analysis results: In group A at 48 weeks, the decreased level of PD-1CXCR5CD4T lymphocyte ratio had no correlation with the decreased level of HBsAg and HBV DNA, but was positively correlated with the decreased level of HBeAg (=0.376, <0.05). The decreased level of sPD-1 had no correlation with the changes of HBsAg, but was positively correlated with the decreased levels of HBeAg and HBV DNA (=0.598 and 0.384, <0.05). In group B at 48 weeks, the decreased levels of PD-1CXCR5CD4T lymphocytes and sPD-1 were positively correlated with the decreased levels of HBsAg, HBeAg, and HBV DNA (<0.05). Hepatitis B virus replication and expressions in HBeAg-positive chronic hepatitis B virus carriers were significantly inhibited after 48 weeks of antiviral treatment, which is related not only to entecavir treatment, but also to the immunological mechanism involved in sPD-1. Moreover, the inhibition of HBeAg expression is associated with a decrease in the number and/or activity of PD-1CXCR5CD4T lymphocytes.
为动态观察恩替卡韦治疗HBeAg阳性慢性乙型肝炎病毒携带者的临床疗效及外周血中PD-1⁺CXCR5⁺CD4⁺T淋巴细胞和sPD-1水平的变化，并进一步探讨其临床意义。治疗组（A）有31例慢性乙型肝炎病毒携带者，治疗组（B）有32例慢性乙型肝炎病毒携带者，非治疗组（C）有15例慢性乙型肝炎病毒携带者。收集三组在0、24和48周时的外周血样本及临床资料并进行比较。采用流式细胞术检测PD-1⁺CXCR5⁺CD4⁺T淋巴细胞，采用酶联免疫吸附试验检测sPD-1水平。对三组间的计量资料进行方差分析和Spearman相关性分析。0周时，A组和C组血清HBsAg、HBeAg和HBV DNA水平显著高于B组。B组外周血PD-1⁺CXCR5⁺CD4⁺T淋巴细胞（4.70%±1.58%）显著高于A组（3.25%±1.01%）和C组（2.77%±0.67%）（F = 16.65，P < 0.05）。A组和C组之间差异无统计学意义（P > 0.05）。B组外周血sPD-1[（1 866.62±1 472.70）pg/ml]显著高于A组[（824.86±538.66）pg/ml]和C组[（618.19±602.62）pg/ml]（F = 10.95，P < 0.05）。A组和C组之间差异无统计学意义（P > 0.05）。48周时，A组和C组血清HBsAg较基线无显著下降（P > 0.05），但显著高于B组（P < 0.05）。A组和B组血清HBeAg水平较基线显著下降（P < 0.05），但A组显著高于B组（P < 0.05），A组和C组之间差异无统计学意义（P > 0.05）。A组和B组血清HBV DNA水平显著低于C组（P < 0.05），A组和B组之间差异无统计学意义（P > 0.05）。A组（1.56%±0.73%）和B组（1.32%±0.43%）外周血PD-1⁺CXCR5⁺CD4⁺T淋巴细胞显著低于C组（2.64%±0.85%）（P < 0.05）。A组[（289.05±215.86）pg/ml]和B组[（236.01±173.92）pg/ml]外周血sPD-1显著低于C组[（650.34±598.46）pg/ml]（P < 0.05）。A组和B组之间差异无统计学意义。相关性分析结果：在48周时的A组中，PD-1⁺CXCR5⁺CD4⁺T淋巴细胞比例下降水平与HBsAg和HBV DNA下降水平无相关性，但与HBeAg下降水平呈正相关（r = 0.376，P < 0.05）。sPD-1下降水平与HBsAg变化无相关性，但与HBeAg和HBV DNA下降水平呈正相关（r = 0.598和0.384，P < 0.05）。在48周时的B组中，PD-1⁺CXCR5⁺CD4⁺T淋巴细胞和sPD-1下降水平与HBsAg、HBeAg和HBV DNA下降水平呈正相关（P < 0.05）。抗病毒治疗48周后HBeAg阳性慢性乙型肝炎病毒携带者的乙型肝炎病毒复制和表达受到显著抑制，这不仅与恩替卡韦治疗有关，还与sPD-1参与的免疫机制有关。此外，HBeAg表达的抑制与PD-1⁺CXCR5⁺CD4⁺T淋巴细胞数量和/或活性的降低有关。
