Consolidation treatment needed for sustained HBsAg-negative response induced by interferon-alpha in HBeAg positive chronic hepatitis B patients

Minghui Li; Fangfang Sun; Xiaoyue Bi; Yanjie Lin; Liu Yang; Yao Lu; Lu Zhang; Gang Wan; Wei Yi; Linqing Zhao; Yao Xie

doi:10.1016/j.virs.2022.03.001

June 2022

Minghui Li, Fangfang Sun, Xiaoyue Bi, Yanjie Lin, Liu Yang, Yao Lu, Lu Zhang, Gang Wan, Wei Yi, Linqing Zhao and Yao Xie. Consolidation treatment needed for sustained HBsAg-negative response induced by interferon-alpha in HBeAg positive chronic hepatitis B patients[J]. Virologica Sinica, 2022, 37(3): 390-397. doi: 10.1016/j.virs.2022.03.001

Citation: Minghui Li, Fangfang Sun, Xiaoyue Bi, Yanjie Lin, Liu Yang, Yao Lu, Lu Zhang, Gang Wan, Wei Yi, Linqing Zhao, Yao Xie. Consolidation treatment needed for sustained HBsAg-negative response induced by interferon-alpha in HBeAg positive chronic hepatitis B patients .VIROLOGICA SINICA, 2022, 37(3) : 390-397. http://dx.doi.org/10.1016/j.virs.2022.03.001

持续HBsAg阴性应答的HBeAg阳性的慢性乙型肝炎患者中干扰素-α巩固治疗的必要性

李明慧 ^a,b ,
孙芳芳 ^a ,
毕潇月 ^a ,
林妍洁 ^b ,
杨柳 ^a ,
路遥 ^a ,
张璐 ^a ,
万钢 ^c ,
易为 ^d,, ,
赵林清 ^e,, ,
谢尧 ^a,b,,

1 首都医科大学附属北京地坛医院肝病二科, 北京, 100015, 中国;
2 北京大学地坛教学医院肝病二科, 北京, 100015, 中国;
3 首都医科大学附属北京地坛医院病案统计科, 北京, 100015, 中国;
4 首都医科大学附属北京地坛医院妇产科, 北京, 100015, 中国;
5 首都儿科研究所病毒研究室, 儿童病毒病病原学北京市重点实验室, 北京 100020, 中国

通讯作者： 易为, yiwei1215@163.com; 赵林清, linqingz525@163.com; 谢尧, xieyao00120184@sina.com
收稿日期： 2021-10-21
录用日期： 2022-02-25

摘要

乙型肝炎表面抗原（HBsAg）清除被认为是慢性乙型肝炎（CHB）患者的功能性治愈。本研究的目的是评估经干扰素治疗获得HBsAg清除的初治的HBeAg阳性的慢乙肝患者的持久性。这是一项前瞻性研究，入组经干扰素治疗获得HBsAg消失的HBeAg阳性的慢乙肝患者，停止干扰素治疗后12周内入组并随访48周。每3-6个月观察病毒学标志物、生化指标和肝脏影像学检查。主要评价指标为持续性功能治愈。还探索与HBsAg持续阴性或复阳相关的因素。持续性HBsAg消失率为91.8%（212/231）。巩固治疗12-24周和≥24周的患者HBsAg持续阴性率高于巩固治疗< 12周的患者（98.3%和91.2%比86.7%，P=0.068），且巩固治疗组的表面抗体水平显著高于巩固治疗< 12周的患者（P < 0.05）。HBsAg和HBV DNA复阳的累积发生率分别为8.2%和3.9%。巩固治疗时间≥ 12周的是持续功能治愈的预测因素（OR：3.318，95% CI：1.077-10.224，P=0.037），而停止干扰素治疗时HBeAg阳性状态是HBsAg复阳的预测因素（OR：12.271，95% CI：1.076-139.919，P=0.043）。HBeAg阳性的慢乙肝患者经干扰素-α治疗获得的功能治愈是持久的，获得HBsAg消失后需要巩固干扰素治疗≥ 12-24周。
- 慢性乙型肝炎(CHB)
- , 功能性治愈
- , HBeAg阳性
- , HBsAg消失
- , 干扰素(IFN)

Consolidation treatment needed for sustained HBsAg-negative response induced by interferon-alpha in HBeAg positive chronic hepatitis B patients

Minghui Li ^a,b ,
Fangfang Sun ^a ,
Xiaoyue Bi ^a ,
Yanjie Lin ^b ,
Liu Yang ^a ,
Yao Lu ^a ,
Lu Zhang ^a ,
Gang Wan ^c ,
Wei Yi ^d,, ,
Linqing Zhao ^e,, ,
Yao Xie ^a,b,,

a Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China;
b Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, 100015, China;
c Department of Biostatistics, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China;
d Department of Gynecology and Obstetrics, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China;
e Laboratory of Virology, Beijing Key Laboratory of Etiology of Viral Diseases in Children, Capital Institute of Pediatrics, Beijing, 100020, China

Corresponding author: Wei Yi, yiwei1215@163.com Linqing Zhao, linqingz525@163.com Yao Xie, xieyao00120184@sina.com
Received Date: 21 October 2021
Accepted Date: 25 February 2022

Abstract

Hepatitis B surface antigen (HBsAg) clearance is considered as functional cure in patients with chronic hepatitis B (CHB). This study aimed to assess the durability of HBsAg clearance achieved by interferon-based therapies in patients with CHB who were originally positive for hepatitis B envelope antigen (HBeAg). In this prospective study, HBeAg-positive CHB patients with confirmed HBsAg loss under interferon-based therapies were enrolled within 12 weeks from end of treatment and followed up for 48 weeks. Virological markers, biochemical indicators, and liver imaging examinations were observed every 3-6 months. Sustained functional cure was analysed as primary outcome. Factor associated with sustained HBsAg loss or reversion was also investigated. The rate of HBsAg loss sustainability was 91.8% (212/231). Patients receiving consolidation treatment for 12-24 weeks or ≥ 24 weeks had higher rates of sustained HBsAg negativity than those receiving consolidation treatment for < 12 weeks (98.3% and 91.2% vs. 86.7%, P=0.068), and the former groups had significantly higher anti-HBs levels than the later (P < 0.05). The cumulative incidence of HBsAg reversion and HBV DNA reversion was 8.2% and 3.9%, respectively. Consolidation treatment of ≥ 12 weeks[odd ratio (OR) 3.318, 95% confidence interval (CI) 1.077-10.224, P=0.037) was a predictor of sustained functional cure, and HBeAg-positivity at cessation of treatment (OR 12.271, 95% CI 1.076-139.919, P=0.043) was a predictor of HBsAg reversion. Interferon-alpha induced functional cure was durable and a consolidation treatment of ≥ 12-24 weeks was needed after HBsAg loss in HBeAg-positive CHB patients.
- Chronic hepatitis B (CHB)
- , Functional cure
- , HBeAg positive
- , HBsAg loss
- , Interferon (IFN)

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