接受聚乙二醇干扰素联合恩替卡韦治疗的慢性乙型肝炎患者

StephenW

The Characteristics of Natural Killer Cells in Chronic Hepatitis B Patients Who Received PEGylated-Interferon versus Entecavir Therapy
Weihua Cao  1   2 , Minghui Li  1   3 , Lu Zhang  1 , Yao Lu  1 , Shuling Wu  1 , Ge Shen  1 , Min Chang  1 , Ruyu Liu  1 , Yuanjiao Gao  1 , Hongxiao Hao  1 , Leiping Hu  1 , Wei Yi  4 , Calvin Q Pan  5   6 , Yao Xie  1   3
Affiliations
Affiliations

    1
    Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Chaoyang, Beijing 100015, China.
    2
    Department of Infectious Diseases, Miyun Teaching Hospital, Capital Medical University, Beijing 101500, China.
    3
    Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, No. 8 Jing Shun East Street, Chaoyang, Beijing 100015, China.
    4
    Department of Obstetrics and Gynecology, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Chaoyang District, Beijing 100015, China.
    5
    Center of Liver Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China.
    6
    Division of Gastroenterology and Hepatology, Department of Medicine, NYU Langone Health, New York University School of Medicine, New York, NY, USA.

    PMID: 33575322 PMCID: PMC7857883 DOI: 10.1155/2021/2178143

Abstract

Background: To explore the role of natural killer (NK) cells in the process of hepatitis B virus (HBV) clearance and whether their phenotype is related to antiviral treatment outcome in chronic hepatitis B (CHB) patients.

Method: We performed a single-center prospective cohort study to analyze changes of NK cells at weeks 12 and 24 from baseline in CHB patients who received PEGylated-interferon- (PEG-IFN-) α-2a versus entecavir. The frequencies of NK, CD56bright, CD56dim, IFNAR2+, NKp46+, NKp46bright, and NKp46dim NK cells and mean fluorescence intensity (MFI) of receptors NKp46 and IFNAR2 on the surface of NK cells were measured. Subgroup analyses were performed by comparing treatment responders versus nonresponders with aforementioned parameters in each group.

Results: In PEG-IFN-α-treated patients, posttreatment CD56bright NK cell frequency increased, but CD56dim NK cell frequency decreased. Additionally, receptor NKp46 and IFNAR2 expression enhanced. In entecavir-treated patients, although NK cell frequency increased, CD56bright and CD56dim NK cell frequencies and IFNAR2 expression did not differ between baseline and posttreatment. In subgroup analyses, posttreatment CD56bright NK cell frequency and IFNAR2 expression significantly increased in PEG-IFN-α responders from baseline, while changes were absent in PEG-IFN-α nonresponders and entecavir treatment responders. Among patients with HBV viremia after entecavir therapy, NK cell frequency significantly increased, whereas NKp46bright and IFNAR2+ NK frequency and IFNAR2 MFI significantly decreased at 12 and 24 weeks from baseline.

Conclusions: In CHB patients, PEG-IFN-α treatment significantly enhanced NK cell frequency and function when compared to entacavir. Positive treatment responses to either interferon or entecavir were associated with NK cell function improvement. This trial is registered with clinical trial registration no. NCT03208998.

Copyright © 2021 Weihua Cao et al.

StephenW

接受聚乙二醇干扰素联合恩替卡韦治疗的慢性乙型肝炎患者的自然杀伤细胞特征
曹卫华1 2，李明慧1 3，陆章1，姚路1，吴淑玲1，申身1，民昌1，刘如玉1，袁教教1，洪晓浩1，胡雷平1，魏一4，卡尔文·潘5 6，姚谢1 3
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科2，北京朝阳静顺东大街8号100015
    2
    首都医科大学附属密云教学医院传染病科，北京101500
    3
    北京大学地坛教学医院第二医院肝病科，北京朝阳静顺东大街8号，北京100015
    4
    首都医科大学附属北京地坛医院妇产科，北京市朝阳区经东东街8号，北京100015
    5
    首都医科大学附属北京地坛医院肝病研究中心，北京100015
    6
    美国纽约大学医学院纽约大学朗格健康分校消化内科和肝病科。

    PMID：33575322 PMCID：PMC7857883 DOI：10.1155 / 2021/2178143

抽象的

背景：探讨自然杀伤（NK）细胞在乙型肝炎病毒（HBV）清除过程中的作用，以及它们的表型是否与慢性乙型肝炎（CHB）患者的抗病毒治疗结果相关。

方法：我们进行了单中心前瞻性队列研究，以分析接受聚乙二醇化干扰素-（PEG-IFN-）α-2a与恩替卡韦治疗的CHB患者在基线第12和24周时NK细胞的变化。测量NK细胞的NK，CD56bright，CD56dim，IFNAR2 +，NKp46 +，NKp46dright和NKp46dim NK的频率以及NK细胞表面受体NKp46和IFNAR2的平均荧光强度（MFI）。通过将治疗应答者与无应答者与每组中上述参数进行比较，进行亚组分析。

结果：在接受PEG-IFN-α治疗的患者中，治疗后CD56亮NK细胞频率增加，而CD56dim NK细胞频率降低。另外，受体NKp46和IFNAR2表达增强。在恩替卡韦治疗的患者中，尽管NK细胞频率增加，但基线和治疗后CD56bright和CD56dim NK细胞频率和IFNAR2表达没有差异。在亚组分析中，PEG-IFN-α应答者的基线治疗后CD56bright NK细胞频率和IFNAR2表达显着增加，而PEG-IFN-α无应答者和恩替卡韦治疗应答者则无变化。在恩替卡韦治疗后的HBV病毒血症患者中，NK细胞频率显着升高，而NKp46bright和IFNAR2 + NK频率和IFNAR2 MFI在距基线12周和24周时显着降低。

结论：与恩替卡韦相比，在CHB患者中，PEG-IFN-α治疗显着增强了NK细胞的频率和功能。对干扰素或恩替卡韦的阳性治疗反应均与NK细胞功能的改善有关。该试验已通过临床试验注册号进行注册。 NCT03208998。

版权所有©2021曹卫华等。

StephenW

https://www.hindawi.com/journals/bmri/2021/2178143/