乙肝病毒感染后不同临床类型及HBV DNA载量与外周血T细胞亚群变化的相关性分析

Correlation between changes in peripheral blood T cell subsets and HBV DNA load in patients with different clinical types of HBV infection

目的探讨乙肝病毒（HBV）感染后不同临床类型乙型肝炎患者及HBV DNA载量与外周血T细胞亚群的关系。方法选取确诊的共193例急性乙型肝炎、慢性乙型肝炎、慢性重型肝炎、亚急性重型肝炎、急性重型肝炎、乙肝肝硬化、乙肝肝癌、HBV携带者的外周血,流式细胞仪检测T细胞亚群,荧光定量PCR法检测HBV DNA水平。结果对照组CD3＋、CD4＋细胞百分率、CD4＋/CD8＋细胞比值明显高于各临床类型组,随病情加重CD3＋、CD4＋细胞百分率、CD4＋/CD8＋细胞比值下降明显,除急性乙型肝炎组和慢性肝炎组CD4＋细胞百分率外与各组比较差异有统计学意义（P〈0.05及P〈0.01）;对照组CD8＋细胞百分率、CD4＋/CD25＋细胞比值明显低于各临床类型组,随病情加重CD8＋细胞百分率、CD4＋/CD25＋细胞比值升高明显,各组比较差异有统计学意义（P〈0.05及P〈0.01）。低水平HBV DNA载量组（≤103 Copies/ml）CD3＋、CD4＋细胞百分率明显高于其他各病毒组,随病毒载量增加CD3＋、CD4＋细胞百分率逐渐减少,与各组比较差异有统计学意义（P〈0.05及P〈0.01）;低水平HBV DNA载量组CD8＋细胞百分率最低,随病毒载量增加CD8＋细胞百分率升高明显,与各组比较差异有统计学意义（P〈0.05及P〈0.01）;低水平HBV DNA载量组CD4＋/CD8＋及CD4＋/CD25＋细胞比值最高,其比值随病毒载量增加下降明显,低水平组CD4＋/CD25＋细胞比值与各组比较差异有统计学意义（P〈0.05及P〈0.01）,低水平组CD4＋/CD8＋细胞比值与各组（103～105组除外）比较差异有统计学意义（P〈0.05及P〈0.01）。除乙肝肝硬化的CD4＋细胞百分率外,同病种肝病的HBV DNA（＋）组CD3＋、CD4＋、CD8＋细胞百分率、CD4＋/CD8＋及CD4＋/CD25＋细胞比值与HBV DNA（-）组比较,差异有统计学意义（P〈0.05及P〈0.01）。结论细胞免疫功能紊乱是HBV感染后发病机制之一,高水平HBV DNA载量可能诱导和加重细胞免疫功能紊乱,CD4＋/CD8＋及CD4＋/CD25＋比值变化可为了解病情变化和指导治疗提供依据。

【Objective】 To investigate the relationship between peripheral blood T cell subsets and HBV DNA load in patients with different clinical types of hepatitis B virus（HBV） infection. 【Methods】 A total of193 cases diagnosed as acute hepatitis B, chronic hepatitis B, chronic severe hepatitis, subacute severe hepatitis, acute severe hepatitis, hepatitis B liver cirrhosis, hepatitis B liver cancer or HBV carriers were enrolled into this study. T cell subsets and HBV DNA load were detected in their peripheral blood using flow cytometry and fluorescence quantitative PCR, respectively. 【Results】 The percentages of CD3＋and CD4＋cells and CD4＋/CD8＋cell ratio in the control group were significantly higher than those in the clinical groups, which significantly decreased along with the increased severity of the diseases; the differences were statistically significant between the control group and the different clinical groups except CD4＋T cell percentage in acute hepatitis B group and chronic hepatitis group（P 〈0.05 and P 〈0.01）. The percentage of CD8＋T cells and CD4＋/CD25＋cells ratio in the control group were lower than those in the clinical groups, which significantly increased as the disease severity increased; the differences were statistically significant between the control group and the different clinical groups（P 〈0.05 and P 〈0.01）. The percentages of CD3＋and CD4＋cells in the low HBV DNA load group（≤103Copies/ml） were significantly higher than those in the groups with higher HBV DNA loads（P 〈0.05 and P 〈0.01）, they gradually decreased with the increase of viral loads. The percentage of CD8＋T cells was the lowest in the low HBV DNA load group and had significant differences compared to that in other groups（P 〈0.05 and P 〈0.01）, it increased obviously with the increase of viral loads.The ratios of CD4＋/CD8＋and CD4＋/CD25＋cells were the highest in the low HBV DNA load group, the ratios significantly decreased with the increase of viral load. The CD4＋/CD25＋cell ratio in the low HBV DNA load group was statistically different from that in other groups（P 〈0.05 and P 〈0.01）, the CD4＋/CD8＋cell ratio in the low HBV DNA load group was significantly different from that in other groups except the group with viral load of 103~105Copies/ml（P 〈0.05 and P 〈0.01）. Except for the percentage of CD4＋cells in the hepatitis B cirrhosis group, the percentages of CD3＋, CD4＋and CD8＋cells and CD4＋/ CD8＋and CD4＋/ CD25＋cell ratios in the HBV DNA（＋） subgroup were statistically different from those in the HBV DNA（-） subgroup of the same liver disease group（P 〈0.05 and P 〈0.05）. 【Conclusions】 Cellular immune dysfunction is one of the pathogenic mechanisms of HBV infection. High level of HBV DNA load may induce and aggravate cellular immune dysfunction. The changes in CD4＋/CD8＋and CD4＋/CD25＋ratios can provide the basis for understanding the change of patient＇s condition and guiding the treatment.