乙型肝炎病毒对不同ALT状态下慢性乙型肝炎患者T淋巴细胞及其亚群的影响

目的：探讨乙型肝炎病毒（HBV）在不同丙氨酸氨基转移酶（ALT）状态下对T淋巴细胞及其亚群的影响，阐明以ALT分组抗病毒治疗乙型肝炎（乙肝）的免疫学机制。方法：选取慢性乙肝患者363例作为研究对象，根据ALT异常情况分为ALT正常组（131例）、ALT大于等于正常上限且小于2倍增高组（110例）和ALT大于等于正常上限2倍增高组（122例）。对ALT大于等于正常上限2倍增高组患者给予恩替卡韦治疗，随访24周。采用化学发光免疫分析仪检测乙肝抗原抗体指标，采用全自动生化分析仪检测肝功能指标，采用全自动荧光定量PCR分析仪检测被测者的病毒载量，采用流式细胞仪检测T淋巴细胞分类，酶联免疫吸附实验（ELISA）法检测患者血清中白细胞介素12（IL-2）、干扰素γ（IFN-γ）、白细胞介素4（IL-4）和白细胞介素10（IL-10）水平，检测不同组别中不同载量HBV对机体免疫学指标的影响及抗病毒治疗前后患者病毒学及免疫学指标的变化。结果：在ALT正常组中，不同载量HBV患者T淋巴细胞总数、Th/i淋巴细胞数、Ts/c淋巴细胞数及血清中IL-2、IFN-γ、IL-4和IL-10水平比较差异无统计学意义（P>0.05）；在ALT大于等于正常上限2倍增高组，随着病毒载量的增加，患者T淋巴细胞总数和Th/i淋巴细胞数明显下降（P<0.05），Ts/c淋巴细胞数明显升高（P<0.05），反映Th1细胞的细胞因子IL-2和IFN-γ水平明显升高（P<0.05），反映Th2细胞的细胞因子IL-4和IL-10水平明显下降（P<0.05）。与治疗前比较，恩替卡韦治疗24周后，患者HBVDNA明显下降（P<0.05），T淋巴细胞总数和Th/i淋巴细胞数明显升高（P<0.05），Ts/c淋巴细胞数明显下降（P<0.05），血清中IL-2和IFN-γ水平明显下降（P<0.05），IL-4和IL-10水平明显升高（P<0.05）。结论：HBV在不同ALT状态下对机体免疫功能有不同的影响，对于ALT大于等于正常上限2倍增高的乙肝患者进行抗病毒治疗可明显改变机体的免疫状态。

Effects of hepatitis B virus on T lymphocytes and their subsets in chronic hepatitis B patients in different ALT states

Objective: To investigate the effects of hepatitis B virus (HBV) on the T lymphocytes and their subsets in different alanine aminetransferase(ALT) states,and to elucidate the immunological mechanism of ALT-based antiviral therapy for hepatitis B. Methods: A total of 363 patients with chronic hepatitis B were selected as the subjects. According to the ALT abnormalities, the patients were divided into ALT normal group (131 cases),normal ≤ ALT<2 times of upper limit group (110 cases),and ALT ≥ 2 times of upper limit group (122 cases).The patients in ALT ≥ 2 times of upper limit group were given entecavir and followed up for 24 weeks.The hepatitis B antigen antibody parameters were measured by chemiluminescence immunoassay analyzer,the liver function parameters were measured by automatic biochemical analyzer,the HBV loads were measured by quantitative PCR analyzer,the classification of T lymphocytes was detected by flow cytometry, and the levels of serum interleukin-2(IL-2),interferon-γ(IFN-γ),interleukin-4(IL-4) and interleukin-10(IL-10) of the patients were detected by enzyme-linked immunosorbent assay(ELISA) method.The influence of different HBV loads in the immunological indexes in various groups and the changes of virological and immunological indexes of the patients before and after antiviral therapy were detected. Results: In ALT normal group, there were no significant differences in the total number of T lymphocytes,the number of Th/i lymphocytes,the number of Ts/c lymphocytes and the serum IL-2,IFN-γ,IL-4,IL-10 levels of the patients with different loads of HBV(P>0.05).In ALT ≥ 2 times of upper limit group, with the increase of virus load,the total number of T lymphocytes and the number of Th/i lymphocytes were decreased(P<0.05),and the number of Ts/c lymphocytes was increased(P<0.05); the cytokines IL-2 and IFN-γ levels were increased(P<0.05),and the cytokines IL-4 and IL-10 levels were decreased(P<0.05).Compared with before treatment,24 weeks atfer entecavir treatment, the patient's HBV DNA was decreased significantly (P<0.05),the total number of T lymphocytes and the number of Th/i lymphocytes were increased(P<0.05), the number of Ts/c lymphocytes was decreased(P<0.05); the cytokines IL-2 and IFN-γ levels were decreased(P<0.05),and the cytokines IL-4 and IL-10 levels were increased(P<0.05). Conclusion: The influence of HBV on immune function is different in different ALT states. Therefore, antiviral therapy for the hepatitis B patients with ALT ≥ 2 times of upper limit can significantly change the immunological state of the patients.