PEG-IFN α-2a 治疗期间 HBeAg 阳性慢性乙型肝炎患者自然杀伤细

StephenW

PEG-IFN α-2a 治疗期间 HBeAg 阳性慢性乙型肝炎患者自然杀伤细胞的功能分子表达与 HBsAg 清除相关
曹卫华 1 2 、陆慧慧 1 3 、张璐雪 1 4 、王世玉 1 、邓文 1 、江婷婷 1 、林艳杰 5 、刘洋 1 、毕晓月 1 、陆耀 1 、张璐 1 、申戈 1 , 刘如玉 1 , Min Chang 1 , 吴淑玲 1 , 高元娇 1 , Hongxiao Hao 1 , Mengjiao Xu 1 , 陈晓雪 1 , Hu Leiping 1 , Yao Xie 1 5 , Minghui Li 1 5
隶属关系
隶属关系

     1个
     首都医科大学附属北京地坛医院肝病二科。
     2个
     【作者单位】： 首都医科大学附属密云教学医院感染科;
     3个
     华中科技大学同济医学院武汉儿童医院（武汉市妇幼保健院）妇产科，武汉，中国。
     4个
     【作者单位】： 首都医科大学附属宣武医院感染科;
     5个
     北京大学地坛教学医院肝病二科，中国北京。

     PMID：36479104 PMCID：PMC9720173 DOI：10.3389/fimmu.2022.1067362

抽象的

目的：探讨乙型肝炎e包膜抗原（HBeAg）阳性慢性乙型肝炎（CHB）患者中自然杀伤细胞（NK细胞）频率及功能分子表达是否与乙型肝炎表面抗原（HBsAg）消失有关。 聚乙二醇干扰素 α-2a (PEG-IFN α-2a) 治疗。

方法：在这项前瞻性研究中，HBeAg 阳性的 CHB 患者接受了 PEG-IFN α-2a 治疗，完成了 4 年的随访。 PEG-IFN α-2a 治疗后，检测不到 HBV DNA、HBsAg 消失和 HBeAg 消失被定义为功能性治愈。 检测了 NK、CD56dim、CD56bright、NKp46+、NKp46dim、NKp46high 和干扰素α受体 2 (IFNAR2)+ NK 细胞的比例，以及 NK 细胞表面受体 IFNAR2 和 NKp46 的平均荧光强度 (MFI)。

结果：66例患者入组，其中17例获得功能性治愈。 基线时，功能性治愈组乙型肝炎病毒脱氧核糖核酸（HBV DNA）滴度明显低于非功能性治愈组。 与基线相比，功能性治愈患者的 HBV DNA 水平、HBsAg 水平和 HBeAg 水平在治疗的第 12 周和第 24 周显着下降。 基线时，CD56bright NK%与HBV DNA呈负相关，CD56dim NK%与HBV DNA呈负相关； 功能治愈患者的CD56bright NK%和IFNAR2 MFI明显高于未功能治愈患者。 治疗后功能治愈患者CD56bright NK%和NKp46high NK%均高于未功能治愈患者。 功能治愈组治疗24周后NK%、CD56bright NK%、IFNAR2 MFI微弱升高，NKp46high NK%和NKp46 MFI明显升高，同时CD56dim NK%和NKp46dim NK%降低。 在没有功能性治愈的患者中，只有 NKp46 MFI 在治疗后增加。

结论：治疗前HBV DNA载量越低、CD56bright NK%越高，治疗后CD56bright NK%、IFNAR2 MFI、NKp46high NK%越高，越容易实现功能性治愈。

关键词：HBsAg 丢失； PEG-IFN α-2a； 慢性乙型肝炎； 乙型肝炎病毒; 自然杀伤细胞。

Copyright © 2022 Cao, Lu, Zhang, Wang, Deng, Jiang, Lin, Yang, Bi, Lu, Zhang, Shen, Liu, Chang, Wu, Gao, Hao, Xu, Chen, Hu, Xie and Li. 版权所有。
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。 审稿人 SR 在审稿时向处理编辑声明与作者有共同的父从属关系。

StephenW

Functional molecular expression of nature killer cells correlated to HBsAg clearance in HBeAg-positive chronic hepatitis B patients during PEG-IFN α-2a therapy
Weihua Cao  1   2 , Huihui Lu  1   3 , Luxue Zhang  1   4 , Shiyu Wang  1 , Wen Deng  1 , Tingting Jiang  1 , Yanjie Lin  5 , Liu Yang  1 , Xiaoyue Bi  1 , Yao Lu  1 , Lu Zhang  1 , Ge Shen  1 , Ruyu Liu  1 , Min Chang  1 , Shuling Wu  1 , Yuanjiao Gao  1 , Hongxiao Hao  1 , Mengjiao Xu  1 , Xiaoxue Chen  1 , Leiping Hu  1 , Yao Xie  1   5 , Minghui Li  1   5
Affiliations
Affiliations

    1
    Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
    2
    Department of Infectious Diseases, Miyun Teaching Hospital, Capital Medical University, Beijing, China.
    3
    Department of Obstetrics and Gynecology, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
    4
    Infectious Disease Department, Xuanwu Hospital, Capital Medical University, Beijing, China.
    5
    Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, China.

    PMID: 36479104 PMCID: PMC9720173 DOI: 10.3389/fimmu.2022.1067362

Abstract

Objective: To explore whether the frequencies and functional molecules expression of Natural Killer cells (NK cells) are related to hepatitis B surface antigen (HBsAg) disappearance in hepatitis B e envelope antigen (HBeAg)-positive patients with chronic hepatitis B (CHB) throughout peginterferon alpha-2a (PEG-IFN α-2a) treatment.

Methods: In this prospective research, HBeAg-positive patients with CHB received PEG-IFN α-2a treatment, completing 4-year follow-up. After PEG-IFN α-2a treatment, undetectable HBV DNA, HBsAg loss, and HBeAg disappearance were defined as functional cure. Proportions of NK, CD56dim, CD56bright, NKp46+, NKp46dim, NKp46high, and interferon alpha receptor 2 (IFNAR2)+ NK cells, and the mean fluorescence intensity (MFI) of NK cell surface receptors IFNAR2 and NKp46 were detected.

Results: 66 patients were enrolled into the study in which 17 patients obtained functional cure. At baseline, hepatitis B virus desoxyribose nucleic acid (HBV DNA) titer in patients with functional cure was remarkably lower than that in Non-functional cure group. Compared with baseline, HBV DNA levels, HBsAg levels, and HBeAg levels significantly declined at week 12 and 24 of therapy in patients with functional cure. At baseline, the negative correlation between CD56bright NK% and HBV DNA and the negative correlation between CD56dim NK% and HBV DNA was showed; CD56bright NK% and IFNAR2 MFI in patients with functional cure were remarkably higher than those in patients without functional cure. After therapy, CD56bright NK% and NKp46high NK% in patients with functional cure were higher than those in patients without functional cure. In Functional cure group, after 24 weeks of treatment NK%, CD56bright NK%, IFNAR2 MFI weakly increased, and NKp46high NK% and NKp46 MFI significantly increased, meanwhile, CD56dim NK% and NKp46dim NK% decreased. Only NKp46 MFI increased after therapy in patients without functional cure.

Conclusion: The lower HBV DNA load and the higher CD56bright NK% before therapy, and the higher the post-treatment CD56bright NK%, IFNAR2 MFI, NKp46high NK%, the easier to achieve functional cure.

Keywords: HBsAg loss; PEG-IFN α-2a; chronic hepatitis B; hepatitis B virus; nature killer cells.

Copyright © 2022 Cao, Lu, Zhang, Wang, Deng, Jiang, Lin, Yang, Bi, Lu, Zhang, Shen, Liu, Chang, Wu, Gao, Hao, Xu, Chen, Hu, Xie and Li.
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 reviewer SR declared a shared parent affiliation with the authors to the handling editor at the time of review.

StephenW

https://www.frontiersin.org/arti ... mu.2022.1067362/pdf