The Research Institute of Infectious Diseases, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, PR China.
Department of Immunology, Medicine College of Lanzhou University, Lanzhou 730000, Gansu Province, PR China.
Int Immunopharmacol. 2021 Dec;101(Pt A):108182. doi: 10.1016/j.intimp.2021.108182. Epub 2021 Oct 1.
The aim of the present study was to explore the effect of hepatitis B virus on T lymphocyte and its subsets in different ALT states, and elucidate the immunological mechanism of ALT basing antiviral therapy for hepatitis B. 363 chronic hepatitis B patients were selected as the study subjects. According to ALT abnormalities, the patients were divided into three study groups. ALT normal group 131 cases, normal≦ ALT < 2 times of upper limit group 110 cases, ALT ≥ 2 times of upper limit group 122 cases. Entecavir was given to the ALT ≥ 2 times of upper limit group patients 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 hepatitis B virus load were measured by quantitative PCR analyzer, T lymphocytes were detected by flow cytometry, the level of IL-2, IFN-γ, IL-4 and IL-10 were detected by enzyme-linked immunosorbent assay. Detecting the influence of different hepatitis B viru loads in different groups on immunological indexes, and the virological and immunological indexes changes in before and after antiviral therapy patients. In the ALT normal group, different virus load hepatitis B virus had minor effect on T lymphocytes and their subsets (P > 0.05). In the ALT ≥ double upper limit of normal group. with the virus load increased, The total number of T lymphocytes, CD3+ CD4 + T lymphocytes decreased, (P < 0.05)CD3+ CD8 + T lymphocytes increased(P < 0.05). With the virus load increased the cytokines IL-2, IFN-γ which reflect the Th1 lymphocytes increased(P < 0.05), the cytokines IL-4、IL-10 which reflect the Th2 lymphocytes decreased(P < 0.05). Before and after 24 weeks of entecavir treatment, the patient's HBV-DNA decreased significantly(P < 0.05) and the body's immune function improved significantly. (P < 0.05)The influence of hepatitis B virus on immune function is different in different ALT states. Therefore, the scientific significance of ALT grouping in the hepatitis B treatment can be clarified from the immunological point.
本研究旨在探讨乙型肝炎病毒在不同 ALT 状态下对 T 淋巴细胞及其亚群的影响，并基于抗病毒治疗乙型肝炎阐明 ALT 的免疫学机制。选择 363 例慢性乙型肝炎患者为研究对象。根据 ALT 异常情况，将患者分为三组。ALT 正常组 131 例，正常≦ALT<2 倍上限组 110 例，ALT≥2 倍上限组 122 例。对 ALT≥2 倍上限组患者给予恩替卡韦，并随访 24 周。采用化学发光免疫分析仪检测乙型肝炎抗原抗体参数，采用自动生化分析仪检测肝功能参数，采用定量 PCR 分析仪检测乙型肝炎病毒载量，采用流式细胞仪检测 T 淋巴细胞，采用酶联免疫吸附试验检测 IL-2、IFN-γ、IL-4 和 IL-10 水平。检测不同组中不同乙型肝炎病毒载量对免疫指标的影响，以及抗病毒治疗前后患者的病毒学和免疫学指标变化。在 ALT 正常组中，不同病毒载量的乙型肝炎病毒对 T 淋巴细胞及其亚群影响较小（P>0.05）。在 ALT≥正常上限两倍组中，随着病毒载量的增加，总 T 淋巴细胞、CD3+CD4+T 淋巴细胞减少（P<0.05），CD3+CD8+T 淋巴细胞增加（P<0.05）。随着病毒载量的增加，反映 Th1 淋巴细胞的细胞因子 IL-2、IFN-γ增加（P<0.05），反映 Th2 淋巴细胞的细胞因子 IL-4、IL-10减少（P<0.05）。恩替卡韦治疗 24 周前后，患者 HBV-DNA 明显下降（P<0.05），机体免疫功能明显改善（P<0.05）。乙型肝炎病毒对免疫功能的影响在不同 ALT 状态下不同。因此，从免疫学角度可以阐明 ALT 分组在乙型肝炎治疗中的科学意义。
