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

StephenW

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。

StephenW

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.

StephenW

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