慢性乙型肝炎及后期肝病患者外周血T淋巴细胞亚群标志的研究

目的 探讨慢性乙型肝炎及其后期肝病患者免疫状态,了解其变化及临床意义。 方法 纳入临床确诊的慢性乙型肝炎(chronic hepatitis B,CHB)患者37例、乙型肝炎后肝硬化(liver cirrhosis,LC)患者35例、乙肝肝癌(hepatocellular cancer,HCC)患者32例及健康对照(healthy controls,HC)38例。流式细胞术检测其外周血T淋巴细胞亚群(CD3⁺、CD3⁺CD4⁺、CD3⁺CD8⁺、CD4⁺ /CD8⁺和Th1、Th2)的构成比,用ELISA法分析各组血清中Th1类(IFN-γ)、Th2类(IL-4)、Th17(IL-17)细胞因子的表达量。 结果 CHB、 LC、HCC与正常对照相比外周血CD3⁺、CD3⁺CD4⁺、CD3⁺CD8⁺、CD4⁺/CD8⁺百分数比例均降低,差异均有统计学意义(P＜0.05或P＜0.01);CHB、 LC、HCC患者TH1(CD4⁺IFN-γ⁺)细胞频率明显低于健康对照(P＜0.05),CHB、 LC、HCC三组患者TH2(CD4⁺IL4⁺)均高于健康对照(P＜0.05); 对应CHB、LC、HCC患者血清IL-4、IL17明显高于健康对照组(P＜0.05),而CHB、LC、HCC患者血清中IFN-γ低于健康对照组(P＜0.05)。慢性乙型肝炎患者病程与淋巴细胞亚群、细胞因子均有明显相关性(均P<0.05)。 结论 慢性乙型肝炎、乙肝肝硬化及肝癌患者外周血存在T细胞亚群标志改变,提示患者免疫功能紊乱,监测免疫功能并纠正免疫紊乱对指导临床有重要意义。

Biomarkers in peripheral blood T-lymphocyte subsets of patients with chronic hepatitis B and its advanced liver diseases

ObjectiveTo explore the immune status of patients with chronic hepatitis B (CHB) and its advanced liver diseases by examining biomarkers in peripheral blood T-lymphocyte subsets, and to evaluate the changes and clinical significance of the biomarkers. Methods Thirty-seven patients with CHB, 35 patients with hepatitis B-associated liver cirrhosis (LC), 32 patients with hepatitis B-associated hepatocellular cancer (HCC) and 38 healthy controls (HC) were enrolled in this study. Flow cytometry was used to detect the percentages of CD3⁺, CD3⁺CD4⁺, CD3⁺CD8⁺, CD4⁺ /CD8⁺, TH1 and TH2 cells in peripheral blood of all subjects.The cytokines of TH1 group(IFN-γ), TH2 group (IL-4) and TH17 group (IL-17) were quantitated by ELISA so as to evaluate the functions of TH1, TH2, and TH17 immune T cells, respectively. Results The percentages of CD3⁺, CD3⁺CD4⁺, CD3⁺CD8⁺, and CD4⁺/CD8⁺ in the groups of CHB, LC and HCC were all lower than those of the control group, with statistically significant differences(P＜0.05 or P＜0.01). The percentages of TH1 (CD4+IFN-γ+) of the groups of CHB, LC and HCC were significantly lower than that of the control group (P<0.05), while the percentages of TH2 (CD4+IL4+) of the groups of CHB, LC and HCC were all higher than that of the control group (P<0.05). The serum levels of cytokines IL-4 and IL17 were significantly higher in the groups of CHB, LC and HCC than in the control group (P<0.05), while the serum level of IFN-γ was lower in the groups of CHB, LC and HCC than in the control group (P<0.05). There was a significant correlation between the duration of CHB illness and T-lymphocyte subsets, cytokines (both P<0.05). Conclusions There exist variations of biomarkers in peripheral blood T-lymphocyte subsets of patients with CHB, hepatitis B-associatedLC and hepatitis B-associatedHCC, and the findings indicate that these patients all have an immune disorder. Therefore, monitoring immune functions and adjusting immune disorder play important roles in guiding clinical practice.