HBV相关肝病患者外周血T细胞及细胞因子水平研究

Peripheral blood T cell and cytokine levels in HBV-related liver disease patients

背景乙型肝炎病毒(hepatitis B virus,HBV)相关慢性肝病患者外周血T细胞及细胞因子水平与患者免疫功能状态密切相关,不同疾病程度的HBV相关肝病患者的T细胞、细胞因子水平及与肝病阶段的相关性值得进一步探究.目的探究不同阶段HBV相关慢性肝病患者外周血T细胞亚群计数、细胞因子变化特点及关联性.方法本研究为一项观察性研究,共纳入慢性乙型肝炎(chronic hepatitis B,CHB)患者65例,肝硬化失代偿期(decompensated cirrhosis,DCC)患者122例,肝细胞癌(hepatocellular carcinoma,HCC)患者109例,收集患者一般信息、病史、治疗情况及实验室检查结果、Child-Paugh分级及HCC患者肿瘤巴塞罗那分期,分析各项指标,尤其是T细胞亚群计数及细胞因子的组间差异及特征.结果HBV相关肝硬化、HCC患者外周血CD8^(+)T细胞水平与Child分级A到C呈负相关.HCC患者CD8^(+)T细胞绝对计数显著低于DCC[240(150-379)cells/μLvs 277(154-435)cells/μL,P<0.05]及CHB[240(150-379)cells/μL vs 452(269-706)cells/μL,P<0.001]患者.白细胞介素(interleukin,IL)-6、IL-8、肿瘤坏死因子(tumor necrosis factor,TNF)-α在HCC组均最高.DCC、HCC患者Child-Paugh分级越差,CD3^(+)、CD8^(+)T细胞水平越低,IL-6水平越高.HCC患者CD3^(+)、CD8^(+)T细胞水平随着肿瘤巴塞罗那分期由A到D呈下降趋势,IL-6呈上升趋势.且肝硬化、HCC患者CD3^(+)(r=-0.340,P<0.001)、CD8^(+)(r=-0.353,P<0.001)T细胞水平与IL-6升高水平呈显著负相关.结论HBV相关肝硬化、HCC患者外周血CD8^(+)T细胞计数与Child分级(由A到C)呈负相关,且IL-6水平与CD8^(+)T细胞计数存在负相关关系.

BACKGROUND The peripheral blood T cell and cytokine levels in patients with hepatitis B virus(HBV)-related chronic liver disease are closely related to their immune function status.The T cell and cytokine levels in patients with different severities of HBV-related liver disease and their correlation with the stage of liver disease deserve further exploration.AIM To investigate the characteristics and correlations of peripheral blood T cell subsets and cytokine changes in patients with HBV-related chronic liver diseases at different stages.METHODS This is an observational study that included 65 patients with chronic hepatitis B(CHB),122 with decompensated cirrhosis(DCC),and 109 with hepatocellular carcinoma(HCC).General patient information,medical history,treatment details,laboratory test results,Child-Pugh classification,and Barcelona Clinic Liver Cancer(BCLC)stage for HCC patients were collected.Various parameters,especially T cell subset counts and cytokine profiles,were analyzed to assess their intergroup differences and features.RESULTS Peripheral blood CD8^(+)T cell levels in HBV-related cirrhosis and HCC patients were negatively correlated with Child-Pugh classification from A to C.The absolute count of CD8^(+)T cells in HCC patients was significantly lower than that in decompensated cirrhosis[240(150-379)cells/μL vs 277(154-435)cells/μL,P<0.05]and CHB patients[240(150-379)cells/μL vs 452(269-706)cells/μL,P<0.001].Interleukin-6(IL-6),interleukin-8(IL-8),and tumor necrosis factorα(TNF-α)levels were highest in the HCC group.In patients with decompensated cirrhosis and HCC,as Child-Pugh classification worsened,CD3^(+)and CD8^(+)T cell levels decreased,and IL-6 levels increased.In HCC patients,CD3^(+)and CD8^(+)T cell levels decreased from BCLC stage A to D,while IL-6 levels increased.Moreover,in patients with cirrhosis and HCC,CD3^(+)(r=-0.340,P<0.001)and CD8^(+)(r=-0.353,P<0.001)T cell levels were significantly negatively correlated with elevated IL-6 levels.CONCLUSION Peripheral blood CD8^(+)T cell counts in patients with HBV-related cirrhosis and HCC are negatively correlated with Child-Pugh classification(from A to C),and there is a negative correlation between IL-6 levels and CD8^(+)T cell counts.