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。作者: StephenW 时间: 2022-12-10 21:03
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.
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.
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. 作者: StephenW 时间: 2022-12-10 21:04