外周血淋巴细胞亚群在慢性HBV感染过程中表达的变化分析

目的探讨HBV感染患者外周血淋巴细胞亚群在疾病进展过程中的表达变化。方法选取2018年1月-2019年4月在天津市第二人民医院住院的慢性HBV感染患者共132例,其中慢性乙型肝炎患者47例,乙型肝炎肝硬化患者44例,乙型肝炎肝硬化相关原发性肝癌患者41例。另选取同期健康体检者42例作为对照组。采用流式细胞术检测4组外周血淋巴细胞亚群精准计数,比较4组外周血淋巴细胞亚群的表达水平。正态分布的计量资料,组间方差不齐采用Welch方差分析,两两比较采用GamesHowell检验。非正态分布的计量资料多组间及进一步两两比较采用Kruskal-Wallis H检验。计数资料组间比较采用χ2检验。相关性分析采用Spearman检验。结果与对照组和慢性乙型肝炎组相比,肝硬化组和肝癌组CD3^+、CD4^+T淋巴细胞数量明显减少,差异均有统计学意义(P值均<0.05)。与对照组相比,肝癌组CD8^+T淋巴细胞数量明显减少,差异有统计学意义(P<0.05);与慢性乙型肝炎组相比,肝硬化组和肝癌组CD8^+T淋巴细胞数量明显减少,差异均有统计学意义(P值均<0.05)。与对照组和慢性乙型肝炎组相比,肝硬化组和肝癌组CD19^+B淋巴细胞数量明显减少,差异均有统计学意义(P值均<0.05)。与对照组相比,肝硬化组和肝癌组CD16^+CD56^+NK细胞数量明显减少,差异均有统计学意义(P值均<0.05);与慢性乙型肝炎组比较,肝癌组CD16^+CD56^+NK细胞数量明显减少,差异有统计学意义(P<0.05)。4组疾病进展与外周血CD3^+T淋巴细胞、CD4^+T淋巴细胞、CD8^+T淋巴细胞、CD19^+B淋巴细胞、CD16^+CD56^+NK细胞呈明显负相关(r值分别为-0.414、-0.503、-0.269、-0.435、-0.402,P值均<0.01)。结论随着疾病的进展,慢性HBV感染患者免疫状态发生变化。外周血淋巴细胞亚群精准计数能够反应机体的免疫状态,可作为慢性HBV感染临床病情演变、治疗效果及疾病预后的参考依据。

Change in the expression of peripheral blood lymphocyte subsets during disease progression in patients with chronic hepatitis B virus infection

Objective To investigate the change in the expression of peripheral blood lymphocyte subsets during disease progression in patients with chronic hepatitis B virus(HBV)infection.Methods A total of 132 patients with chronic HBV infection who were hospitalized in Tianjin Second People’s Hospital from January 2018 to April 2019 were enrolled,and among these patients,47 had chronic hepatitis B,44 had hepatitis B cirrhosis(cirrhosis group),and 41 had hepatitis B cirrhosis-related primary liver cancer(liver cancer group).A total of 42 healthy individuals who underwent physical examination during the same period of time were enrolled as control group.Flow cytometry was used to measure the accurate counts of peripheral blood lymphocyte subsets,and the expression of peripheral blood lymphocyte subsets was compared between the four groups.A Welch analysis of variance was used for comparison of normally distributed continuous data with heterogeneity of variance between groups,and the Games-Howell test was used for further comparison between two groups.The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between groups.The chi-square test was used for comparison of categorical data between groups.A Spearman correlation analysis was used to investigate correlation.Results Compared with the control group and the chronic hepatitis B group,the cirrhosis group and the liver cancer group had significant reductions in the numbers of CD3^+and CD4^+T cells(all P<0.05).Compared with the control group,the liver cancer group had a significant reduction in the number of CD8^+T cells(P<0.05);compared with the chronic hepatitis B group,the cirrhosis group and the liver cancer group had a significant reduction in the number of CD8^+T cells(both P<0.05).Compared with the control group and the chronic hepatitis B group,the cirrhosis group and the liver cancer group had a significant reduction in the number of CD19^+B cells(all P<0.05).Compared with the control group,the cirrhosis group and the liver cancer group had a significant reduction in the number of CD16^+CD56^+natural killer(NK)cells(both P<0.05);compared with the chronic hepatitis B group,the liver cancer group had a significant reduction in the number of CD16^+CD56^+NK cells(P<0.05).In the four groups,disease progression was negatively correlated with peripheral blood CD3^+T cells,CD4^+T cells,CD8^+T cells,CD19^+B cells,and CD16^+CD56^+NK cells(r=-0.414,-0.503,-0.269,-0.435,and-0.402,all P<0.01).Conclusion In patients with chronic HBV infection,immune status changes with disease progression.Accurate counting of peripheral blood lymphocyte subsets can reflect the immune status of the body and can thus be used as a reference for evaluating clinical evolution,treatment outcome,and prognosis of chronic HBV infection.