HBeAg 阳性慢性乙型肝炎感染患者停用口服抗病毒药物后的持

StephenW

HBeAg 阳性慢性乙型肝炎感染患者停用口服抗病毒药物后的持续病毒反应和复发
孙芳芳 1 2 、李振华 3 、胡蕾平 1 、邓文 1 、江婷婷 1 、王世玉 1 、毕晓月 1 、卢慧慧 1 4 、刘洋 1 、林艳杰 5 、曾展 5 、申戈 1 、 刘如玉 1，常敏 1，吴淑玲 1，高元娇 1，郝红晓 1，徐梦娇 1，陈晓雪 1，张璐 1，吕耀 1，董建平 2，谢耀 1 5，李明辉 1 5
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二科。
     2个
     北京大学第三医院北京市海淀区海淀医院感染科，中国北京。
     3个
     首都医科大学附属北京地坛医院妇产科，中国北京。
     4个
     华中科技大学同济医学院武汉儿童医院（武汉市妇幼保健院）妇产科，武汉，中国。
     5个
     北京大学地坛教学医院肝病二科，中国北京。

     PMID：36505492 PMCID：PMC9732422 DOI：10.3389/fimmu.2022.1082091

抽象的

目的：探讨乙型肝炎e抗原（HBeAg）阳性慢性乙型肝炎（CHB）患者停用口服抗病毒药物后的持续病毒学应答及复发情况，监测疾病进展及肝硬化、肝硬化等不良事件发生情况。 肝细胞癌。

方法：这是一项前瞻性观察研究。 入组了在实现 HBeAg 血清学转换 3 年以上后继续核苷（酸）类似物 (NA) 治疗的患者。 签署知情同意书后，患者停止NA治疗并接受随访。 随访期间收集患者的抗病毒治疗信息，自入组后每3个月进行一次随访观察。 随访期间监测病毒学指标、肝肾功能、血清学和肝脏影像学。 本研究旨在探讨停药后持续病毒学应答率、HBV DNA复发率、临床复发率及相关因素。

结果：共纳入82例患者，其中男性42例（51.22%），女性40例（48.78%），中位年龄34.00（31.00，37.25）岁。 所有入组患者均随访 1 年。 随访结束时，36.59%（30/82）的患者出现持续病毒学应答，63.41%（52/82）的患者出现HBV DNA再激活，17.07%（14/82）的患者出现临床复发， 10.98% (9/82) 的患者出现 HBeAg 逆转。 随访期间未发生肝硬化、肝细胞癌等不良事件。 持续病毒学应答患者乙型肝炎表面抗原（HBsAg）中位水平低于HBV DNA再激活患者（2.92 vs.3.18 log10IU/ml，Z=-1.492/P=0.136），中位水平 HBV DNA再激活患者的基线HBsAg低于临床复发患者（3.01 vs.3.45 log10IU/mL，Z=-1.795/P=0.073），但差异无统计学意义。 持续病毒学应答和HBV DNA再激活患者的中位总治疗时间无显着统计学差异[69.50（56.25，86.00）vs.62.50（44.00，88.50）个月，Z=-0.689/P=0.491]， 巩固治疗时间[41.50（36.75，54.75）比40.50（36.00，53.75）个月，Z=-0.419/P=0.675]。

结论：HBeAg阳性CHB患者停止口服抗病毒治疗后的持续病毒学应答率较低，且多见于HBsAg水平较低的患者。 停止 NA 治疗后仍需要密切监测患者。

关键词：乙肝病毒DNA； 乙肝抗原； 慢性乙型肝炎； 临床复发； 核苷（酸）类似物； 持续的病毒学反应。

版权所有 © 2022 Sun, Li, Hu, Deng, Jiang, Wang, Bi, Lu, Yang, Lin, Zeng, Shen, Liu, Chang, Wu, Gao, Hao, Xu, Chen, Zhang, Lu, Dong, Xie and Li .
利益冲突声明

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 YL 在审稿时向处理编辑声明与作者有共同的父母关系。

StephenW

Sustained viral response and relapse after discontinuation of oral antiviral drugs in HBeAg-positive patients with chronic hepatitis B infection
Fangfang Sun  1   2 , Zhenhua Li  3 , Leiping Hu  1 , Wen Deng  1 , Tingting Jiang  1 , Shiyu Wang  1 , Xiaoyue Bi  1 , Huihui Lu  1   4 , Liu Yang  1 , Yanjie Lin  5 , Zhan Zeng  5 , Ge Shen  1 , Ruyu Liu  1 , Min Chang  1 , Shuling Wu  1 , Yuanjiao Gao  1 , Hongxiao Hao  1 , Mengjiao Xu  1 , Xiaoxue Chen  1 , Lu Zhang  1 , Yao Lu  1 , Jianping Dong  2 , 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, Haidian Hospital, Beijing Haidian Section of Peking University Third Hospital, Beijing, China.
    3
    Department of Gynecology and Obstetrics, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
    4
    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.
    5
    Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, China.

    PMID: 36505492 PMCID: PMC9732422 DOI: 10.3389/fimmu.2022.1082091

Abstract

Objective: To investigate the sustained virological response and relapse in chronic hepatitis B (CHB) patients with hepatitis B e antigen (HBeAg) positive after stopping oral antiviral drugs, and to monitor the disease progression and the incidence of adverse events such as liver cirrhosis and hepatocellular carcinoma.

Methods: This is a prospective observational study. Patients who continued nucleos(t)ide analogue (NA) treatment after achieving HBeAg seroconversion for more than 3 years were enrolled. After signing the informed consent form, patients stopped NA treatment and received follow-up. During the follow-up, the antiviral treatment information of the patients was collected, and the follow-up observation was carried out every 3 months since the enrollment. We monitored the virological indexes, liver and kidney function, serology and liver imaging during follow-up. The purpose of this study was to explore the sustained virological response rate, HBV DNA recurrence rate, clinical relapse rate and the related factors after drug withdrawal.

Results: A total of 82 patients were enrolled, including 42 males (51.22%) and 40 females (48.78%), with a median age of 34.00 (31.00, 37.25) years. All enrolled patients were followed up for 1 year. At the end of the follow-up, 36.59% (30/82) of patients had sustained virological response, 63.41% (52/82) of patients had HBV DNA reactivation, 17.07% (14/82) of patients had clinical relapse, and 10.98% (9/82) of patients had HBeAg reversion. During the follow-up, there were no adverse events such as liver cirrhosis and hepatocellular carcinoma. The median level of hepatitis B surface antigen (HBsAg) in patients with sustained virological response was lower than that in patients with HBV DNA reactivation (2.92 vs.3.18 log10IU/ml, Z=-1.492/P=0.136), and the median level of baseline HBsAg in patients with HBV DNA reactivation was lower than that in patients with clinical relapse (3.01 vs.3.45 log10IU/mL, Z=-1.795/P=0.073), but the difference was not significant. There was no significant statistical difference between patients with sustained virological response and HBV DNA reactivation of the median total treatment time [69.50 (56.25, 86.00) vs.62.50 (44.00, 88.50) months, Z=-0.689/P=0.491], and the consolidation treatment time [41.50 (36.75, 54.75) vs.40.50 (36.00, 53.75) months, Z=-0.419/P=0.675].

Conclusion: The sustained virological response rate of HBeAg positive CHB patients after stopping oral antiviral treatment is lower, and it is more common in patients with lower HBsAg levels. Patients still need to be closely monitored after stopping NA therapy.

Keywords: HBV DNA; HBeAg; chronic hepatitis B; clinical relapse; nucleos(t)ide analogue; sustained virological response.

Copyright © 2022 Sun, Li, Hu, Deng, Jiang, Wang, Bi, Lu, Yang, Lin, Zeng, Shen, Liu, Chang, Wu, Gao, Hao, Xu, Chen, Zhang, Lu, Dong, Xie and Li.
Conflict of interest statement

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 YL declared a shared parent affiliation with the authors to the handling editor at the time of review.

StephenW

https://www.frontiersin.org/arti ... mu.2022.1082091/pdf