改善慢性乙型肝炎患者核苷酸类似物停药后复发的预测

StephenW

Improving the prediction of relapse after nucleos(t)ide analogue discontinuation in patients with chronic hepatitis B
Do Seon Song  1   2 , Jeong Won Jang  1   2 , Sun Hong Yoo  1   2 , Jung Hyun Kwon  1   2 , Soon Woo Nam  1   2 , Si Hyun Bae  1   2 , Jong Young Choi  1   2 , Seung Kew Yoon  1   2
Affiliations
Affiliations

    1
    Division of Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
    2
    The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea.

    PMID: 33417679 DOI: 10.1093/cid/ciab007

Abstract

Background: Current guidelines recommend rules for stopping nucleos(t)ide analogues (NAs) in chronic hepatitis B (CHB) patients, but off-therapy relapse is still high. This study aimed to identify predictors of off-therapy relapse and improve existing stopping rules.

Methods: This retrospective study included 488 CHB patients (262 HBeAg-positive and 226 HBeAg-negative) who discontinued NAs. Post-treatment relapse was investigated.

Results: During the median follow-up period of 73.3 months, the cumulative 5-year and 10-year virologic relapse (VR) rates were 73.5% and 76.1%, respectively. In HBeAg-positive patients, end-of-therapy hepatitis B surface antigen (HBsAg) levels (hazard ratio [HR], 1.93; 95% confidence interval [CI], 1.42-2.61) and consolidation duration ≥2 years (HR, 0.31; 95% CI, 0.17-0.58) were independent predictors of VR. Consolidation ≥2 years and low HBsAg levels (≤560 IU/mL) significantly lowered VR rates. In HBeAg-negative patients, only the HBsAg level (HR, 1.61; 95% CI, 1.24-2.11) was independently predictive of VR. Cirrhosis was significantly associated with higher VR rates in HBeAg-negative patients with low HBsAg levels (≤800 IU/mL). Combining end-of-therapy HBsAg levels with current stopping rules or consolidation duration further reduced off-therapy relapse, with 2-year VR rates of approximately 15%-25% in HBeAg-positive patients and 50% in HBeAg-negative patients.

Conclusions: End-of-therapy HBsAg levels, consolidation duration, and cirrhosis are key determinants of off-therapy relapse. Together with low HBsAg levels, extended consolidation therapy for ≥2 years should be ensured, and cirrhotic patients should continue NAs even if low HBsAg levels are achieved. A combination of these parameters will help identify individuals at low risk of relapse and significantly improve the predictive ability of the existing stopping rules.

Keywords: antiviral therapy; cessation; chronic hepatitis B; relapse.

© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected].

StephenW

改善慢性乙型肝炎患者核苷酸类似物停药后复发的预测
杜善颂1 2，郑源章1 2，孙洪Yo 1 2，郑贤权1 2，顺宇南1 2，时贤贝1 2，钟英才1 2，成邱园1 2
隶属关系
隶属关系

    1个
    韩国天主教大学医学院内科学系肝病科，首尔。
    2
    韩国首尔天主教大学医学院天主教大学肝脏研究中心。

    PMID：33417679 DOI：10.1093 / cid / ciab007

抽象

背景：目前的指南推荐了在慢性乙型肝炎（CHB）患者中停止使用核苷酸（t）类似物（NAs）的规则，但非治疗复发率仍然很高。这项研究旨在确定非治疗复发的预测因素，并改善现有的停止规则。

方法：这项回顾性研究包括488例中断NAs的CHB患者（262 HBeAg阳性和226 HBeAg阴性）。治疗后复发进行了调查。

结果：在73.3个月的中位随访期中，5年和10年累计病毒学复发率分别为73.5％和76.1％。在HBeAg阳性患者中，治疗结束后的乙肝表面抗原（HBsAg）水平（危险比[HR]为1.93； 95％置信区间[CI]为1.42-2.61），巩固期≥2年（HR为0.31） ； 95％CI（0.17-0.58）是VR的独立预测因子。合并≥2年和低HBsAg水平（≤560IU / mL）可显着降低VR率。在HBeAg阴性患者中，只有HBsAg水平（HR，1.61； 95％CI，1.24-2.11）独立预测VR。 HBsAg水平低（≤800IU / mL）的HBeAg阴性患者中，肝硬化与较高的VR率显着相关。将治疗结束时的HBsAg水平与当前的停药规则或合并持续时间相结合，可进一步减少非治疗复发，HBeAg阳性患者的2年VR率约为15％-25％，HBeAg阴性患者的50％。

结论：治疗结束后HBsAg水平，巩固持续时间和肝硬化是决定治疗后复发的关键因素。与低HBsAg水平一起，应确保延长巩固治疗≥2年，并且即使达到低HBsAg水平，肝硬化患者也应继续NAs。这些参数的组合将有助于识别复发风险低的个体，并显着提高现有停止规则的预测能力。

关键词：抗病毒治疗；戒烟慢性乙型肝炎复发。

©2021年作者，牛津大学出版社，美国传染病学会出版。版权所有。有关权限，请发送电子邮件至：[email protected]。