慢性乙型肝炎患者乙型肝炎e抗原丢失的核苷酸（t）ide类似物

StephenW

Exploration of nucleos(t)ide analogs cessation in chronic hepatitis B patients with hepatitis B e antigen loss
Yan Xue  1 , Meng Zhang  1 , Tao Li  1 , Feng Liu  2 , Li-Xin Zhang  1 , Xiao-Ping Fan  1 , Bao-Hua Yang  1 , Lei Wang  3
Affiliations
Affiliations

    1
    Department of Infectious Disease and Hepatology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250033, Shandong Province, China.
    2
    Department of Hepatology, Tianjin Second People's Hospital, Tianjin 300000, China.
    3
    Department of Infectious Disease and Hepatology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250033, Shandong Province, China. [email protected].

    PMID: 33911470 PMCID: PMC8047530 DOI: 10.3748/wjg.v27.i14.1497

Abstract

Background: Nucleos(t)ide analogs (NAs) cessation in chronic hepatitis B (CHB) patients remains a matter of debate in clinical practice. Current guidelines recommend that patients with hepatitis B e antigen (HBeAg) seroconversion discontinue NAs after relatively long-term consolidation therapy. However, many patients fail to achieve HBeAg seroconversion after the long-term loss of HBeAg, even if hepatitis B surface antigen (HBsAg) loss occurs. It remains unclear whether NAs can be discontinued in this subset of patients.

Aim: To investigate the outcomes and factors associated with HBeAg-positive CHB patients with HBeAg loss (without hepatitis B e antibody) after cessation of NAs.

Methods: We studied patients who discontinued NAs after achieving HBeAg loss. The Cox proportional hazards model was used to identify predictors for virological relapse after cessation of NAs. The cut-off value of the consolidation period was confirmed using receiver operating characteristic curves; we confirmed the cut-off value of HBsAg according to a previous study. The log-rank test was used to compare cumulative relapse rates among groups. We also studied patients with CHB who achieved HBeAg seroconversion and compared their cumulative relapse rates. Propensity score matching analysis (PSM) was used to balance baseline characteristics between the groups.

Results: We included 83 patients with HBeAg loss. The mean age of these patients was 32.1 ± 9.5 years, and the majority was male (67.5%). Thirty-eight patients relapsed, and the cumulative relapse rate at months 3, 6, 12, 24, 36, 60, 120, and 180 were 22.9%, 36.1%, 41.0%, 43.5%, 45.0%, 45.0%, 45.0%, and 52.8%, respectively. Twenty-six (68.4%) patients relapsed in the first 3 mo after NAs cessation, and 35 patients (92.1%) relapsed in the first year after NAs cessation. Consolidation period (≥ 24 mo vs < 24 mo) (HR 0.506, P = 0.043) and HBsAg at cessation (≥ 100 IU/mL vs < 100 IU/mL) (HR 14.869, P = 0.008) were significant predictors in multivariate Cox regression. In the PSM cohort, which included 144 patients, there were lower cumulative relapse rates in patients with HBeAg seroconversion (P = 0.036).

Conclusion: HBeAg-positive CHB patients with HBeAg loss may be able to discontinue NAs therapy after long-term consolidation, especially in patients with HBsAg at cessation < 100 IU/mL. Careful monitoring, especially in the early stages after cessation, may ensure a favorable outcome.

Keywords: Cessation; Chronic hepatitis B; Hepatitis B e antigen; Nucleos(t)ide analogs.

©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.

StephenW

慢性乙型肝炎患者乙型肝炎e抗原丢失的核苷酸（t）ide类似物的探索
严雪1，张萌1，陶丽1，刘凤2，张立新1，范小平1，杨宝华1，王雷3
隶属关系
隶属关系

    1个
    山东大学奇卢医学院第二医院传染病和肝病科，山东济南250033
    2个
    天津市第二人民医院肝科，天津300000
    3
    山东大学奇卢医学院第二医院传染病与肝病科，山东济南250033 [email protected]。

    PMID：33911470 PMCID：PMC8047530 DOI：10.3748 / wjg.v27.i14.1497

抽象的

背景：慢性乙型肝炎（CHB）患者停止使用核苷类似物（NAs）仍是临床实践中的一个争论的问题。目前的指南建议，经过相对长期的巩固治疗后，患有乙型肝炎e抗原（HBeAg）血清转换的患者应停用NAs。然而，即使发生乙型肝炎表面抗原（HBsAg）丢失，许多患者在长期丢失HBeAg后也无法实现HBeAg血清转换。尚不清楚在该亚组患者中是否可以停用NAs。

目的：调查与NAs停止后HBeAg阳性（无乙肝e抗体）的HBeAg阳性CHB患者相关的结局和影响因素。

方法：我们研究了达到HBeAg丧失后中止NAs的患者。使用Cox比例风险模型确定NA终止后病毒学复发的预测因素。合并期的临界值使用接收器的工作特性曲线确定。我们根据先前的研究证实了HBsAg的临界值。使用对数秩检验来比较各组之间的累积复发率。我们还研究了实现HBeAg血清转化的CHB患者，并比较了其累积复发率。倾向得分匹配分析（PSM）用于平衡各组之间的基线特征。

结果：我们纳入了83例HBeAg丢失的患者。这些患者的平均年龄为32.1±9.5岁，大多数为男性（67.5％）。 38例患者复发，第3、6、12、24、36、60、120和180个月的累积复发率分别为22.9％，36.1％，41.0％，43.5％，45.0％，45.0％，45.0％ ，和52.8％。停止NAs后的前3个月中有26例（68.4％）复发，而停止NAs后的第一年中有35例（92.1％）复发。巩固期（≥24 mo vs <24 mo）（HR 0.506，P = 0.043）和停药时HBsAg（≥100 IU / mL vs <100 IU / mL）（HR 14.869，P = 0.008）是多变量Cox的重要预测指标回归。在包括144名患者的PSM队列中，HBeAg血清转化患者的累积复发率较低（P = 0.036）。

结论：HBeAg阳性的HBeAg丢失的CHB患者在长期巩固后可能能够停止NAs治疗，尤其是在HBsAg停止<100 IU / mL的患者中。仔细的监测，尤其是在戒烟后的早期阶段，可以确保取得良好的结果。

关键词：戒烟；慢性乙型肝炎；乙型肝炎e抗原；核苷类似物。

©2021年作者。百世登出版集团有限公司出版。保留所有权利。

StephenW

https://www.wjgnet.com/1007-9327/full/v27/i14/1497.htm