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[乙型肝炎病毒对不同丙氨酸氨基转移酶水平阶段Th17、调节性T细胞及Th17/调节性T细胞比值的影响]

[Effects of hepatitis B virus on Th17, Treg and Th17/Treg ratio in different alanine aminetransferase stages].

作者信息

Gao P, Luo Y P, Li J F, Chen I, Mao X R

机构信息

Infectious Disease Research Institute, First Hospital of Lanzhou University, Lanzhou 730000, China.

Department of Immunology, Medicine College of Lanzhou University, Lanzhou 730000, China.

出版信息

Beijing Da Xue Xue Bao Yi Xue Ban. 2022 Apr 18;54(2):272-277. doi: 10.19723/j.issn.1671-167X.2022.02.012.

Abstract

OBJECTIVE

To evaluate the effects of hepatitis B virus (HBV) on helper T lymphocytes 17 (Th17), regulatory T lymphocyte (Treg) and Th17/Treg ratio in chronic hepatitis B patients in different alanine aminetransferase (ALT) stages.

METHODS

In the study, 336 chronic hepatitis B patients in the first hospital of Lanzhou University were analyzed. 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, Th17, Treg and Th17/Treg ratios were detected by flow cytometry. Among them, 111 cases (ALT < 40 U/L) of ALT were normal hepatitis B, 108 cases of chronic hepatitis B with ALT above normal upper limit and < 2 times higher (40 U/L≤ALT < 80 U/L), and 117 cases of chronic hepatitis B with ALT above 2 times normal upper limit (80 U/L≤ALT). According to the viral load, they were divided into low replication group with HBV DNA < 4.0 lg copies/mL, medium replication group with 4.0 lg copies/mL≤HBV DNA < 6.0 lg copies/mL and high replication group with HBV DNA ≥ 6.0 lg copies / mL. Dunnett T3 variance analysis were used to analyze the effects of HBV on Th17, Treg and Th17/Treg ratio in the chronic hepatitis B patients in different ALT stages. The changes of virological and immunological indexes before and after treatment were observed for 24 weeks of antiviral therapy in the hepatitis B patients with ALT≥double upper limit of normal group.

RESULTS

In the ALT normal group, different virus load HBV had minor effects on Th17, Treg and Th17/Treg ratio. In the ALT≥2 times upper limit of normal group, with the virus load increased, Th17 (3.18%±0.79% in low replication group, 3.78%±0.92% in medium replication group and 4.57%±1.15% in high replication group), Treg cells (5.52%±1.58% in low replication group, 5.89%±1.84% in medium replication group and 6.37%±2.35% in high replication group) and their ratio Th17/Treg (0.57±0.25 in low replication group, 0.65±0.29 in medium replication group and 0.73±0.36 in high replication group) were significantly increased ( < 0.05). After entecavir treatment 24 weeks, the patient' s HBV-DNA decreased significantly, Th17 (3.89%±1.02% . 2.06%±0.46%), Treg (6.02%±2.03% . 5.06%±1.25%), Th17/Treg ratio (0.65±0.28 . 0.41±0.14) decreased significantly ( < 0.05).

CONCLUSION

Investigation on the effects of HBV on Th17 and Treg cells and their ratios in different ALT states can clarify the effects of HBV on the body from the immunological perspective and can further understand the ALT grouping for antiviral treatment theoretical significance, which is helpful for clinical treatment.

摘要

目的

评估乙型肝炎病毒(HBV)对不同丙氨酸氨基转移酶(ALT)水平的慢性乙型肝炎患者辅助性T淋巴细胞17(Th17)、调节性T淋巴细胞(Treg)及Th17/Treg比值的影响。

方法

本研究分析了兰州大学第一医院的336例慢性乙型肝炎患者。采用化学发光免疫分析仪检测乙肝抗原抗体参数,自动生化分析仪检测肝功能参数,定量PCR检测HBV载量,流式细胞术检测Th17、Treg及Th17/Treg比值。其中,ALT正常的乙肝患者111例(ALT<40 U/L),ALT高于正常上限且<正常上限2倍(40 U/L≤ALT<80 U/L)的慢性乙型肝炎患者108例,ALT高于正常上限2倍(80 U/L≤ALT)的慢性乙型肝炎患者117例。根据病毒载量,将其分为HBV DNA<4.0 lg拷贝/mL的低复制组、4.0 lg拷贝/mL≤HBV DNA<6.0 lg拷贝/mL的中复制组和HBV DNA≥6.0 lg拷贝/mL的高复制组。采用Dunnett T3方差分析不同ALT水平的慢性乙型肝炎患者中HBV对Th17、Treg及Th17/Treg比值的影响。对ALT≥正常上限2倍组的乙肝患者进行24周抗病毒治疗,观察治疗前后病毒学和免疫学指标的变化。

结果

在ALT正常组,不同病毒载量的HBV对Th17、Treg及Th17/Treg比值影响较小。在ALT≥正常上限2倍组,随着病毒载量增加,Th17(低复制组为3.18%±0.79%,中复制组为3.78%±0.92%,高复制组为4.57%±1.15%)、Treg细胞(低复制组为5.52%±1.58%,中复制组为5.89%±1.84%,高复制组为6.37%±2.35%)及其比值Th17/Treg(低复制组为0.57±0.25,中复制组为0.65±0.29,高复制组为0.73±0.36)均显著升高(P<0.05)。恩替卡韦治疗24周后,患者的HBV-DNA显著下降,Th17(3.89%±1.02% 降至2.06%±0.46%)、Treg(6.02%±2.03% 降至5.06%±1.25%)、Th17/Treg比值(0.65±0.28 降至0.41±0.14)均显著下降(P<0.05)。

结论

研究HBV在不同ALT状态下对Th17和Treg细胞及其比值的影响,可从免疫学角度阐明HBV对机体的作用,进一步理解ALT分组对抗病毒治疗的理论意义,有助于临床治疗。

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