HBeAg 阳性慢性乙型肝炎恩替卡韦治疗 48 周期间细胞因子谱和

StephenW

HBeAg 阳性慢性乙型肝炎恩替卡韦治疗 48 周期间细胞因子谱和病毒学标志物的动态变化
李明辉 1 2 , 高元娇 1 , 刘洋 1 , 林艳杰 2 , 文登 1 , 姜婷婷 1 , 毕晓月 1 , 姚璐 1 , 张璐 1 , 葛深 1 , 刘如玉 1 , 吴淑玲 1 , 闵常 1 , 许梦娇 1 , 雷平湖 1 , 瑞松 3 , 姜玉勇 4 , 卫毅 5 , 姚燮 1 2
隶属关系
隶属关系

    1
    【作者单位】： 首都医科大学北京地坛医院肝病二科;
    2
    【作者单位】： 北京大学地坛教学医院肝病二科;
    3
    【作者单位】： 首都医科大学北京地坛医院感染科;
    4
    【作者单位】： 首都医科大学北京地坛医院中西医结合中心;
    5
    【作者单位】： 首都医科大学北京地坛医院妇产科;

    PMID：36203581 PMCID：PMC9531241 DOI：10.3389/fimmu.2022.1024333

抽象的

目的：本研究旨在探讨恩替卡韦（ETV）抗病毒治疗过程中血清、病毒学和免疫学标志物的动力学变化，并探讨这些指标是否可以预测ETV对乙型肝炎e抗原（HBeAg）的抗病毒作用-阳性慢性乙型肝炎（CHB）患者。

方法：入组 HBeAg 阳性 CHB 患者并接受 ETV 0.5 mg/天治疗。在基线和 48 周治疗期间每 12 周进行临床生化、病毒学和血清学检测。在基线测量细胞因子（Flt-3L、IFN-α2、IFN-γ、IL-10、IL-17A、IL-6、TGF-β1、TGF-β2、TGF-β3 和 TNF-α）的血浆水平在治疗后 12 周和 24 周。对这些临床指标在ETV抗病毒治疗中的趋势进行了分析。

结果：共入组105例HBeAg阳性CHB患者，其中100例完成了48周的ETV治疗和随访。治疗48周后，7例患者乙肝s抗原（HBsAg）下降≥1 log10，但无一例患者HBsAg消失。 13例患者血清学HBeAg消失，3例患者血清学HBeAg转变。病毒学完全缓解组基线HBsAg和HBeAg水平、HBV DNA载量、IL-10、TGF-β1水平低于病毒学不完全缓解组，而病毒学完全缓解组ALT水平高于病毒学完全缓解组。在不完全病毒学反应组中。单变量分析和多变量分析均显示基线生化指标、病毒学指标和细胞因子水平与48周时的完全病毒学应答无相关性。在多变量分析中，低基线 HBV DNA 载量以及 HBeAg 和 IL-10 水平与 ETV 治疗 48 周后 ALT 正常化显着相关（HBeAg OR = 1.003，95% CI 1.001-1.006，p = 0.007；HBV DNA OR = 0.184, 95% CI 0.046-0.739, p = 0.017；IL-10 OR = 0.040, 95% CI 0.972-0.999, p = 0.040)。

结论：细胞因子水平在 ETV 抗病毒治疗期间发生动态变化。 ETV 治疗 48 周后，低基线 HBV DNA 载量、HBeAg 和 IL-10 水平与 ALT 正常化显着相关。

关键词：慢性乙型肝炎；细胞因子；脱氧核糖核酸；恩替卡韦；乙型肝炎e抗原。

版权所有 © 2022 李、高、杨、林、邓、姜、毕、卢、张、沉、刘、吴、常、徐、胡、宋、姜、易、谢。
利益冲突声明

作者声明，该研究是在没有任何可能被解释为潜在利益冲突的商业或财务关系的情况下进行的。编辑在审阅时声明与作者有共同的父母关系。

StephenW

Dynamic changes of cytokine profiles and virological markers during 48 weeks of entecavir treatment for HBeAg-positive chronic hepatitis B
Minghui Li  1   2 , Yuanjiao Gao  1 , Liu Yang  1 , Yanjie Lin  2 , Wen Deng  1 , Tingting Jiang  1 , Xiaoyue Bi  1 , Yao Lu  1 , Lu Zhang  1 , Ge Shen  1 , Ruyu Liu  1 , Shuling Wu  1 , Min Chang  1 , Mengjiao Xu  1 , Leiping Hu  1 , Rui Song  3 , Yuyong Jiang  4 , Wei Yi  5 , Yao Xie  1   2
Affiliations
Affiliations

    1
    Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
    2
    Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, China.
    3
    Department of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
    4
    Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
    5
    Department of Gynecology and Obstetrics, Beijing Ditan Hospital, Capital Medical University, Beijing, China.

    PMID: 36203581 PMCID: PMC9531241 DOI: 10.3389/fimmu.2022.1024333

Abstract

Objective: The aims of this study were to investigate the kinetic changes of serum, virological, and immunological markers during entecavir (ETV) antiviral therapy and to explore whether these indicators can predict the antiviral efficacy of ETV in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients.

Methods: HBeAg-positive CHB patients were enrolled and treated with ETV 0.5 mg/day. Clinical biochemical, virological, and serological tests were performed at baseline and every 12 weeks during the 48-week treatment. Plasma levels of cytokines (Flt-3L, IFN-α2, IFN-γ, IL-10, IL-17A, IL-6, TGF-β1, TGF-β2, TGF-β3, and TNF-α) were measured at baseline and at 12 and 24 weeks after treatment. Analysis of the trends of these clinical indicators in ETV antiviral therapy was performed.

Results: A total of 105 HBeAg-positive CHB patients were enrolled, and 100 of them completed 48 weeks of ETV treatment and follow-up. After 48 weeks of treatment, hepatitis B s antigen (HBsAg) decline ≥ 1 log10 was found in seven patients, but no patient achieved HBsAg disappearance. serological HBeAg disappeared in 13 patients, and serological HBeAg transformed in 3 patients. The baseline HBsAg and HBeAg levels, HBV DNA load, IL-10, and TGF-β1 levels in the complete virological response group were lower than those in the incomplete virological response group, while the ALT level in the complete virological response group was higher than that in the incomplete virological response group. Both univariate analysis and multivariate analysis showed that baseline biochemical indexes, virological indexes, and cytokine levels had no correlation with the complete virological response at 48 weeks. In multivariate analysis, low baseline HBV DNA load, and HBeAg and IL-10 levels were significantly associated with ALT normalization after 48 weeks of ETV treatment (HBeAg OR = 1.003, 95% CI 1.001-1.006, p = 0.007; HBV DNA OR = 0.184, 95% CI 0.046-0.739, p = 0.017; IL-10 OR = 0.040, 95% CI 0.972-0.999, p = 0.040).

Conclusion: Cytokine levels changed dynamically during ETV antiviral therapy. Low baseline HBV DNA load, and HBeAg and IL-10 levels were significantly associated with ALT normalization after 48 weeks of ETV treatment.

Keywords: chronic hepatitis B; cytokines; deoxyribose nucleic acid; entecavir; hepatitis B e antigen.

Copyright © 2022 Li, Gao, Yang, Lin, Deng, Jiang, Bi, Lu, Zhang, Shen, Liu, Wu, Chang, Xu, Hu, Song, Jiang, Yi and Xie.
Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The editor declared a shared parent affiliation with the authors at the time of review.

StephenW

https://www.frontiersin.org/arti ... mu.2022.1024333/pdf