聚乙二醇化干扰素-α联合核苷类似物治疗可增强经历过慢性

StephenW

Combination of Pegylated-Interferon-Alpha and Nucleos(t)ide Analogue Treatment Enhances the Activity of Natural Killer Cells in Nucleos(t)ide Analogue Experienced Chronic Hepatitis B Patients
Xichen Pang  1 , Li Zhang  1 , Nianqiu Liu  1 , Bin Liu  1 , Zhiwei Chen  1 , Hu Li  1 , Min Chen  1 , Mingli Peng  1 , Hong Ren  1 , Peng Hu  1
Affiliations
Affiliation

    1
    Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

    PMID: 32638357 DOI: 10.1111/cei.13486

Abstract

Background & aims: A combination of pegylated interferon-alpha (Peg-IFN-α) and nucleos(t)ides analogue (NA) therapy can effectively reduce hepatitis B surface antigen (HBsAg), especially in NA-experienced chronic hepatitis B (CHB) patients. However, the immune mechanism of this therapy is unclear.

Methods: 40 NA-experienced CHB patients were enrolled in this study. The frequencies of peripheral blood NK cells, DCs, CD4+ T cells, CD8+ T cells, Th cells, Treg cells, B cells and Tfh cells were evaluated by flow cytometry.

Results: 7 of the 40 patients converted to Peg-IFN-α combined with NAs treatment, while the other 33 continued to NAs therapy. The decrease in HBsAg was more pronounced in the combination treatment group, and only patients receiving combination treatment achieved HBsAg loss. The frequency and absolute number of CD56bri NK cells in the combination treatment group increased significantly compared with the NAs treatment group, whereas the CD56dim NK cells were decreased. In the NAs treatment group, the proportions of CD4+ TN cells, CD8+ TN cells, CD19+ B cells and CTLA-4+ CD4+ T cells were increased, while the proportions of CD4+ TEM cells, CD8+ TEM cells, CD25+ CD4+ Treg cells, CD25hi CD4+ Treg cells, CD127low CD25+ Treg cells, PD-1+ CD4+ T cells, PD-1+ CD8+ T cells, CTLA-4+ CD8+ T cells, CCR4+ CD25+ Treg cells and CCR4+ CD25hi Treg cells were decreased after therapy.

Conclusions: For NA-experienced CHB patients who achieved low HBsAg levels, combination treatment is more likely to result in HBsAg decline and HBsAg clearance by increasing the activity of CD56bri NK cells.

Keywords: Chronic Hepatitis B; HBsAg loss; Natural killer cells; Nucleos(t)ide analogues; Pegylated-interferon-alpha.

StephenW

聚乙二醇化干扰素-α联合核苷类似物治疗可增强经历过慢性乙型肝炎患者的核苷类似物的天然杀伤细胞活性
庞喜辰1，张莉1，刘念秋1，刘斌1，陈志伟1，胡莉1，陈敏1，彭明丽1，洪仁1，胡鹏1
隶属关系
联系

    1个
    重庆医科大学附属第二医院，病毒性肝炎研究所传染病科，传染病分子生物学重点实验室，中国教育部

    PMID：32638357 DOI：10.1111 / cei.13486

抽象

背景与目的：聚乙二醇化干扰素-α（Peg-IFN-α）和核苷类似物（NA）治疗的组合可有效减少乙型肝炎表面抗原（HBsAg），尤其是在无NA的慢性乙型肝炎（CHB）中） 耐心。但是，这种疗法的免疫机制尚不清楚。

方法：本研究招募了40名NA经验丰富的CHB患者。通过流式细胞术评估外周血NK细胞，DC，CD4 + T细胞，CD8 + T细胞，Th细胞，Treg细胞，B细胞和Tfh细胞的频率。

结果：40例患者中有7例转用Peg-IFN-α联合NAs治疗，其余33例继续使用NAs治疗。在联合治疗组中，HBsAg的降低更为明显，只有接受联合治疗的患者才达到HBsAg的降低。与NAs治疗组相比，联合治疗组中CD56bri NK细胞的频率和绝对数量显着增加，而CD56dim NK细胞减少。在NAs治疗组中，CD4 + TN细胞，CD8 + TN细胞，CD19 + B细胞和CTLA-4 + CD4 + T细胞的比例增加，而CD4 + TEM细胞，CD8 + TEM细胞，CD25 + CD4 + Treg细胞，CD25hi CD4 +治疗后Treg细胞，CD127low CD25 + Treg细胞，PD-1 + CD4 + T细胞，PD-1 + CD8 + T细胞，CTLA-4 + CD8 + T细胞，CCR4 + CD25 + Treg细胞和CCR4 + CD25hi Treg细胞减少。

结论：对于NA经验不足的HBsAg水平较低的CHB患者，联合治疗更有可能通过增加CD56bri NK细胞的活性而导致HBsAg下降和HBsAg清除。

关键字：慢性乙型肝炎； HBsAg丢失；天然杀伤细胞；核苷类似物；聚乙二醇化干扰素-α。