目的探讨HBeAg阳性慢性乙型肝炎(CHB)患者CD4^+和CD8^+效应T淋巴细胞表面程序性坏死受体-1(PD-1)的表达与临床指标的关系及其在抗病毒治疗中的变化。方法选择2013年1月至2014年6月在郑州大学第一附属医院感染科接受替比夫定抗病毒治疗的56例HBeAg阳性CHB患者,动态监测基线、抗病毒治疗24、48和72周时的PD-1水平。应用t检验比较不同ALT水平、HBV DNA水平及HBeAg转阴前后PD-1表达水平的差异,并采用完全随机方差分析比较PD-1在CD4^+和CD8^+效应T淋巴细胞表面水平的差异。结果治疗基线,CD4^+和CD8^+效应T淋巴细胞表面的PD-1表达水平在丙氨酸转氨酶(ALT)〈90 U/L组均显著高于ALT≥90 U/L组的患者(t=12.20和9.69,P值均〈0.01);而HBV DNA≥5lgIU/mL组患者的CD4^+和CD8^+效应T淋巴细胞表面PD-1表达水平显著高于HBV DNA〈5 lgIU/mL组患者(t=4.39和4.85,P值均〈0.01)。在基线、抗病毒治疗24、48及72周时,CD4^+和CD8^+效应T淋巴细胞表面的PD-1表达水平均呈进行性下降(F=6.98和8.97,P〈0.01)。获得HBeAg转阴的CHB患者CD4^+和CD8^+效应T淋巴细胞表面PD-1表达水平较基线均显著降低(t=18.45和18.01,P值均〈0.01)。结论HBeAg阳性CHB患者经替比夫定抗病毒治疗后,CD4^+及CD8^+效应T淋巴细胞表面的PD-1表达水平呈进行性下降,获得HBeAg转阴患者的PD-1水平较基线显著降低,提示获得HBeAg转阴患者体内免疫抑制状况出现改善。
Objective To investigate the expression of PD-1 on CD4 ^+ and CD8 ^+ T cells in patients with HBeAg-positive chronic hepatitis B(CHB) treated with telbivudine. Methods Fifty-six HBeAg-positive CHB patients admitted in the First Affiliated Hospital of Zhengzhou University during January 2013 and June 2014 were enrolled in this study. The expression of PD-1 on CD4 + and CD8 + T cells was detected with flow cytometry at baseline, 24, 48 and 72 wks after telbivudine treatment. The relationship of PD-1 expression with alanine aminotransferase (ALT) level, HBeAg seroconversion and HBV DNA loads was analyzed, t test and completely random variance analysis were used to analyze the data. Results The PD-1 expression on CD4 + and CD8 ^+ T cells at baseline was higher in patients with low ALT levels compared to those with high ALT levels(t = 12.20 and 9.69,both P 〈0.01 ) ,while higher levels of PD-1 expression was also observed in patients with high HBV DNA load (≥5 lgIU/mL) compared to those with low HBV DNA load (t = d. 39 and 4.85, both P 〈 0.01). PD-1 levels on CD4 + and CD8 ^+ T cells presented a declining trend after telbivudine treatment( F = 6. 98 and 8.97, both P 〈 0.01 ), PD-I expression in patients with HBeAg seroconversion showed lower levels compared with baseline values (t = 18.45 and 18.01, both P 〈0.01 ). Conclusion In HBeAg-positive CHB patients, the expression of PD-1 on CD4 ^+ and CD8 ^+ T lymphocytes shows a decreasing trend during the treatment with telbivudine, indicating that antiviral therapy may alleviate the immunosnppression in these patients.