慢性乙型肝炎病毒感染者外周血T细胞亚群及NK细胞的特点及意义

Characteristic and clinical significance of peripheral blood T cells subsets and NK cells in patients with chronic hepatitis B

目的探讨慢性乙型肝炎病毒(hepatitis B virus,HBV)感染者外周血T细胞亚群及NK细胞的特点及临床意义。方法采用流式细胞术检测各研究组,包括慢性乙型肝炎(chronic hepatitis B,CHB)组33例、乙型肝炎失代偿期肝硬化(liver cirrhosis,LC)组20例、慢性乙型重型肝炎(chronic severe hepati-tis B,CSH)组17例及健康对照组(Control)20例的外周血T细胞亚群及NK细胞相对计数,并检测肝功能、HBVDNA含量及HBV血清标志物。结果按Control、CHB、LC、CSH顺序,CD3+T细胞、CD8+T细胞百分比依次升高,而CD4+T细胞、CD4+/CD8+比值及NK细胞百分比依次降低,且CHB、LC、CSH组与Control组及CHB组与CSH组相比,差异均有统计学意义(P<0.05或P<0.008)。CHB患者的CD3+T细胞与血清总胆红素(total bilirubin,TB)、HBV DNA含量(log10)呈正相关(P<0.001;P<0.001);CD8+T细胞与HBVDNA含量(log10)呈正相关(P=0.007),NK细胞与HBVDNA含量(log10)(P=0.001)呈负相关。CHB组乙型肝炎e抗原(HBeAg)阳性者的CD4+T细胞及CD4+/CD8+比值低于HBeAg阴性者(P=0.018;P<0.001),而HBV DNA含量(log10)和CD8+T细胞高于HBeAg阴性者(P=0.012;P=0.019)。结论慢性HBV感染者外周血T细胞亚群及NK细胞相对值紊乱,且与临床类型、病情、血清HBV DNA水平及HBeAg相关。

Objective To study the characteristic and clinical significance of peripheral blood T ceils subsets and NK cells in patients with chronic hepatitis B. Methods Thirty-three patients with chronic hepatitis B （CHB）, twenty hepatitis B patients with decompensated liver cirrhosis （LC）, seventeen patients with chronic severe hepatitis B （CSH） and 20 healthy controls （Control） were enrolled for observation. The peripheral blood T cells subsets and NK cells were determined by flow cytometry, liver functions were assayed on automatic biochemistry analyzer, serum HBV DNA was amplified by real-time fluorescent quantitative PCR and serum HBV markers were examined by ELISA. Results The percentage of CD3^＋T and CD8^＋T cells in Control, CHB, LC and CSH groups increased gradually,while the percentage of CD4^＋T and NK ceils and the ratio of CD4^＋/CD8^＋ reduced gradually. The differences between CHB and control, LC and control, CSH and control, CHB and CSH were statistically significant （P 〈 0.05 or P 〈 0. 008） in percentages of CD3^＋ T cells, CD4^＋ T cells, CD8^＋ T cells,NK cells and the ratio of CD4^＋/CD8^＋. In the patients with chronic hepatitis B, the correlations between CD3^＋T cells and serum total bilirubin （TB）, CD3^＋T cells and HBV DNA, CD8^＋ T cells and HBV DNA showed positive trend （ P 〈 0. 001 ; P 〈 0. 001 ; P = 0. 007）, while the correlation between NK cells and HBV DNA was negative （ P = 0. 001 ）. Meanwhile, in chronic hepatitis B patients with positive hepatitis B e antigen （HBeAg）, the percentage of CD4^＋T cells and the ratio of CD4^＋ ＋/CD8^＋ were significantly lower （P =0.018 ;P 〈0.001 ）, but HBV DNA and the percentage of CD8 ^＋ T cells were considerably higher （P = 0.012 ;P = 0.019） than those with negative HBeAg. Conclusions Aberrant T cells subsets and NK cells exist in chronic hepatitis B patients which correlate with clinical types, pathogenetic conditions, serum HBV DNA load and HBeAg.