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标题: HBeAg 阳性慢性乙型肝炎患者聚乙二醇干扰素 α-2a 治疗期间与 [打印本页]

作者: StephenW    时间: 2022-5-23 20:02     标题: HBeAg 阳性慢性乙型肝炎患者聚乙二醇干扰素 α-2a 治疗期间与

HBeAg 阳性慢性乙型肝炎患者聚乙二醇干扰素 α-2a 治疗期间与 HBsAg 丢失相关的细胞因子谱和病毒学标志物的动态变化
李明辉 1 2 , 张璐雪 3 , 思燮 4 , 孙方方 1 , 曾增 2 , 文登 1 , 蒋婷婷 1 , 毕晓月 1 , 林延杰 2 , 刘洋 1 , 姚璐 1 , 葛深 1 , 如玉刘 1 , 吴淑玲 1 , 闵昌 1 , 雷平湖 1 , 建平东 5 , 卫毅 6 , 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】: 首都医科大学宣武医院感染科;
    4
    清华大学临床医学院北京清华长庚医院肝胆胰中心肝病科
    5
    【作者单位】: 北京大学第三医院北京海淀区海淀医院感染科;
    6
    【作者单位】: 首都医科大学北京地坛医院妇产科;

    PMID:35603222 PMCID:PMC9114800 DOI:10.3389/fimmu.2022.892031

抽象的

目的:探讨聚乙二醇干扰素α-2a(PEG-IFNα-2a)治疗乙型肝炎e抗原(HBeAg)阳性慢性乙型肝炎(CHB)过程中与乙型肝炎表面抗原(HBsAg)丢失相关的细胞因子和病毒学标志物的动态变化。耐心。

方法:这是一项单中心前瞻性队列研究。 HBeAg 阳性 CHB 患者是前瞻性和连续入组的。在 PEG-IFN 治疗的基线、第 12 周和第 24 周检测到细胞因子。 HBsAg 消失率是 PEG-IFN 治疗 48 周时的主要评价指标。

结果:完成 48 周 PEG-IFNα-2a 治疗的 100 例患者中,38 例患者血清 HBeAg 消失,25 例 HBeAg 血清学转换,9 例功能治愈,37 例 HBsAg 下降≥1 log IU/ml ,8名患者产生乙型肝炎表面抗体(HBsAb)。基线时临床治愈组白蛋白(ALB)、fms样酪氨酸激酶3配体(FLT3-L)和干扰素α2(IFN-α2)明显低于非临床治愈组。治疗12周后,临床治愈组HBsAg明显低于非临床治愈组(中位数1.14 vs. 3.45 log10IU/ml,Z=-4.355,P<0.001)。临床治愈组 HBsAg 和乙型肝炎病毒脱氧核糖核酸(HBV DNA)下降明显高于非临床治愈组(中位数:HBsAg 1.96 vs. 0.33 log10IU/ml,Z =-4.703,P < 0.001;HBV DNA 4.49 vs.3.13 log10IU/ml,Z=-3.053,P=0.002)。治愈组IFN-α2的升高明显高于非临床治愈组(497.89 vs. 344.74,Z=-2.126,P=0.034)。治疗24周后,临床治愈组的HBsAg、HBeAg、Flt3-L和IL-10明显低于非临床治愈组(中位数:HBsAg 0.70 vs. 3.15 log10IU/ml,Z= -4.535,P< 0.001;HBeAg 1.48 对 13.72 S/CO,Z = 2.512,P = 0.012;Flt3-l 0.00 对 2.24 pg/ml,Z = 3.137,P=0.002;IL-10 0.70 对 2.71 pg /ml,Z=-4.067,P < 0.001)。与非临床治愈组相比,临床治愈组的 HBsAg 显着降低(中位数 3.27 vs. 0.45,Z=-4.463,P < 0.001)。

结论:早期 PEG IFN α-2a 治疗期间细胞因子和病毒学标志物的动态变化与 HBeAg 阳性 CHB 患者的 HBsAg 消失有关。

关键词:慢性乙型肝炎;细胞因子;功能性治愈;乙型肝炎表面抗原;干扰素。

Copyright © 2022 Li, Zhang, Xie, Sun, Zeng, Deng, Jiang, Bi, Lin, Yang, Lu, Shen, Liu, Wu, Chang, Hu, Dong, Yi and Xie。
作者: StephenW    时间: 2022-5-23 20:02

Dynamic Changes of Cytokine Profiles and Virological Markers Associated With HBsAg Loss During Peginterferon Alpha-2a Treatment in HBeAg-Positive Chronic Hepatitis B Patients
Minghui Li 1 2 , Luxue Zhang 3 , Si Xie 4 , Fangfang Sun 1 , Zhan Zeng 2 , Wen Deng 1 , Tingting Jiang 1 , Xiaoyue Bi 1 , Yanjie Lin 2 , Liu Yang 1 , Yao Lu 1 , Ge Shen 1 , Ruyu Liu 1 , Shuling Wu 1 , Min Chang 1 , Leiping Hu 1 , Jianping Dong 5 , Wei Yi 6 , 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
    Infectious Disease Department, Xuanwu Hospital, Capital Medical University, Beijing, China.
    4
    Division of Hepatology, Hepato-Pancreato-Biliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.
    5
    Department of Infectious Diseases, Haidian Hospital, Beijing Haidian Section of Peking University Third Hospital, Beijing, China.
    6
    Department of Gynecology and Obstetrics, Beijing Ditan Hospital, Capital Medical University, Beijing, China.

    PMID: 35603222 PMCID: PMC9114800 DOI: 10.3389/fimmu.2022.892031

Abstract

Objective: To explore dynamic changes of cytokines and virological markers associated with hepatitis B surface antigen (HBsAg) loss during peginterferon alpha-2a (PEG-IFN α-2a) treatment in hepatitis B e antigen (HBeAg) positive chronic hepatitis B (CHB) patients.

Methods: It was a single-center prospective cohort study. HBeAg-positive CHB patients were prospectively and consecutively enrolled. Cytokines were detected at baseline, week 12 and 24 of PEG-IFN treatment. HBsAg disappearance rate was the primary evaluation index at 48 weeks of PEG-IFN treatment.

Results: Among 100 patients who completed the 48-week PEG-IFN α-2a treatment, 38 patients achieved serum HBeAg disappearance, 25 patients achieved HBeAg seroconversion, 9 patients achieved functional cure, 37 patients had HBsAg decline of ≥1 log IU/ml , and 8 patients produced hepatitis B surface antibody (HBsAb). Albumin (ALB), fms-like tyrosine kinase 3 ligand (FLT3-L) and interferon-alpha2 (IFN-α2) in the clinical cure group were significantly lower than those in the non-clinical-cure group at baseline. After 12 weeks of treatment, HBsAg in the clinical cure group was significantly lower than that in the non-clinical-cure group (median 1.14 vs. 3.45 log10IU/ml, Z=-4.355, P < 0.001). The decrease of HBsAg and hepatitis B virus desoxyribose nucleic acid (HBV DNA) in the clinical cure group was significantly higher than that in non-clinical-cure group (median: HBsAg 1.96 vs. 0.33 log10IU/ml, Z =-4.703, P< 0.001; HBV DNA 4.49 vs.3.13 log10IU/ml, Z=-3.053, P=0.002). The increase of IFN-α2 in the cure group was significantly higher than that in the non-clinical-cure group (497.89 vs. 344.74, Z=-2.126, P=0.034). After 24 weeks of treatment, HBsAg, HBeAg, Flt3-L, and IL- 10 in the clinical cure group were significantly lower than those in the non-clinical-cure group (median: HBsAg 0.70 vs. 3.15 log10IU/ml, Z=-4.535, P< 0.001; HBeAg 1.48 vs. 13.72 S/CO, Z = 2.512, P = 0.012; Flt3-l 0.00 vs 2.24 pg/ml, Z = 3.137, P=0.002; IL-10 0.70 vs. 2.71 pg/ml, Z=-4.067, P < 0.001). HBsAg decreased significantly in the clinical cure group compared with non-clinical-cure group (median 3.27 vs. 0.45, Z=-4.463, P < 0.001).

Conclusion: Dynamic changes of cytokines and virology markers during early PEG IFN α-2a treatment were associated with HBsAg loss in HBeAg-positive CHB patients.

Keywords: chronic hepatitis B; cytokine; functional cure; hepatitis B surface antigen; interferon.

Copyright © 2022 Li, Zhang, Xie, Sun, Zeng, Deng, Jiang, Bi, Lin, Yang, Lu, Shen, Liu, Wu, Chang, Hu, Dong, Yi and Xie.
作者: StephenW    时间: 2022-5-23 20:03

https://www.frontiersin.org/arti ... mmu.2022.892031/pdf




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