慢性乙型肝炎患者停用核苷（酸）类似物后的停药反应：一

StephenW

慢性乙型肝炎患者停用核苷（酸）类似物后的停药反应：一项国际、多中心、多种族队列（RETRACT-B 研究）
Grishma Hirode 1 , Hannah Sj Choi 2 , Chien-Hung Chen 3 , Tung-Hung Su 4 , Wai-Kay Seto 5 , Stijn Van Hees 6 , Margarita Papatheodoridi 7 , Sabela Lens 8 , Grace Wong 9 , Sylvia R M Braken - Nan Chien 11，Jordan Feld 1，Milan Sonneveld 10，Henry Ly Chan 9，Xavier Forns 8，George V Papatheodoridis 7，Thomas Vanwolleghem 6，Man-Fung Yuen 5，Yao-Chun Hsu 12，Jia-Horng Mark Kao 4， Cornberg 13 , Bettina E Hansen 14 , Wen-Jei Jeng 11 , Harry LA Janssen 15 , RETRACT-B 学习组
隶属关系
隶属关系

    1
    多伦多肝病中心，多伦多总医院，大学健康网络，加拿大；加拿大多伦多大学医学科学研究所；加拿大多伦多病毒性肝炎护理网络 (VIRCAN)。
    2
    多伦多肝病中心，多伦多总医院，大学健康网络，加拿大；加拿大多伦多大学医学科学研究所。
    3
    台湾高雄长庚纪念医院。
    4
    台湾国立台湾大学医院。
    5
    香港大学医学系和肝脏研究国家重点实验室，中国香港特别行政区。
    6
    比利时安特卫普安特卫普大学医院胃肠病学和肝病科。
    7
    希腊雅典国立和卡波迪斯特里安大学医学院。
    8
    巴塞罗那医院诊所、IDIBAPS 和 CIBEREHD，西班牙巴塞罗那大学。
    9
    香港中文大学，香港特别行政区，中国。
    10
    荷兰鹿特丹 Erasmus MC 大学医学中心胃肠病学和肝病学系。
    11
    台湾林口长庚大学长庚纪念医院林口医学中心胃肠肝病科。
    12
    台湾义大医院/义守大学。
    13
    德国汉诺威医学院胃肠病学、肝病学和内分泌学系；德国汉诺威个体感染医学中心 (CiiM)。
    14
    多伦多肝病中心，多伦多总医院，大学健康网络，加拿大；加拿大多伦多病毒性肝炎护理网络 (VIRCAN)。
    15
    多伦多肝病中心，多伦多总医院，大学健康网络，加拿大；加拿大多伦多大学医学科学研究所；加拿大多伦多病毒性肝炎护理网络 (VIRCAN)。电子地址：[email protected]。

    PMID：34762906 DOI：10.1053/j.gastro.2021.11.002

抽象的

背景和目的：由乙型肝炎表面抗原 (HBsAg) 消失定义的功能性治愈在核苷（酸）类似物 (NA) 治疗期间很少见，并且关于有限 NA 治疗的指南尚未完善。我们的目标是在大型、国际、多中心、多种族的慢性乙型肝炎 (CHB) 患者队列中分析停止 NA 后的治疗后结果。

方法：该队列研究包括乙型肝炎 e 抗原 (HBeAg) 阴性并停止 NA 治疗的病毒抑制型 CHB 患者。主要结果是 NA 停止后 HBsAg 消失，次要结果包括病毒学、生化和临床复发、ALT 升高、再治疗和 NA 停止后肝脏相关事件。

结果：在 1,552 名 CHB 患者中，HBsAg 消失的累积概率在 12 个月时为 3.2%，在随访 48 个月时为 13.0%。高加索人（与亚洲人相比：SHR 6.8；95% CI 2.7-16.8；P < .001）和治疗结束时 HBsAg 水平 <100 IU/mL 的患者（与 ≥100 IU/mL）的 HBsAg 消失率更高：SHR 22.5；95% CI 13.1-38.7；P < .001）。在 48 个月的随访中，HBsAg 水平 <1000 IU/mL 的白种人和治疗结束时 HBsAg 水平 <100 IU/mL 的亚洲人具有较高的 HBsAg 消失预测概率 (>30%)。肝功能失代偿和肝细胞癌 (HCC) 的发生率分别为 0.48/1000 人年和 0.29/1000 人年。 7/19 失代偿患者和 2/14 HCC 患者发生死亡。

结论： NA 戒断的最佳候选者是病毒抑制、HBeAg 阴性、HBsAg 水平低的非肝硬化 CHB 患者，特别是 <1000 IU/mL 的白种人和 <100 IU/mL 的亚洲人。但是，建议进行严格的监视以防止恶化。

关键词：乙肝病毒； HBsAg 血清学转换；抗病毒物质;停产。

版权所有 © 2021 AGA 研究所。由 Elsevier Inc. 出版。保留所有权利。

StephenW

Off-therapy response after nucleos(t)ide analogue withdrawal in patients with chronic hepatitis B: An international, multi-center, multi-ethnic cohort (RETRACT-B study)
Grishma Hirode  1 , Hannah Sj Choi  2 , Chien-Hung Chen  3 , Tung-Hung Su  4 , Wai-Kay Seto  5 , Stijn Van Hees  6 , Margarita Papatheodoridi  7 , Sabela Lens  8 , Grace Wong  9 , Sylvia M Brakenhoff  10 , Rong-Nan Chien  11 , Jordan Feld  1 , Milan Sonneveld  10 , Henry Ly Chan  9 , Xavier Forns  8 , George V Papatheodoridis  7 , Thomas Vanwolleghem  6 , Man-Fung Yuen  5 , Yao-Chun Hsu  12 , Jia-Horng Kao  4 , Markus Cornberg  13 , Bettina E Hansen  14 , Wen-Juei Jeng  11 , Harry LA Janssen  15 , RETRACT-B study group
Affiliations
Affiliations

    1
    Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Canada; Institute of Medical Science, University of Toronto, Canada; The Toronto Viral Hepatitis Care Network (VIRCAN), Canada.
    2
    Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Canada; Institute of Medical Science, University of Toronto, Canada.
    3
    Kaohsiung Chang Gung Memorial Hospital, Taiwan.
    4
    National Taiwan University Hospital, Taiwan.
    5
    Department of Medicine and State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong, SAR, China.
    6
    Department of Gastroenterology and Hepatology, Antwerp University Hospital, Antwerp, Belgium.
    7
    Medical School of National and Kapodistrian University of Athens, Greece.
    8
    Hospital Clinic Barcelona, IDIBAPS and CIBEREHD, University of Barcelona, Spain.
    9
    The Chinese University of Hong Kong, Hong Kong, SAR, China.
    10
    Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, Netherlands.
    11
    Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital Linkou Medical Center, Chang Gung University, Linkou, Taiwan.
    12
    E-Da Hospital/I-Shou University, Taiwan, Taiwan.
    13
    Department of Gastroenterology, Hepatolology and Endocrinology, Hannover Medical School, Germany; Centre for Individualized Infection Medicine (CiiM), Hannover, Germany.
    14
    Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Canada; The Toronto Viral Hepatitis Care Network (VIRCAN), Canada.
    15
    Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Canada; Institute of Medical Science, University of Toronto, Canada; The Toronto Viral Hepatitis Care Network (VIRCAN), Canada. Electronic address: [email protected].

    PMID: 34762906 DOI: 10.1053/j.gastro.2021.11.002

Abstract

Background and aims: Functional cure, defined by hepatitis B surface antigen (HBsAg) loss, is rare during nucleos(t)ide analogue (NA) therapy and guidelines on finite NA therapy have not been well established. We aim to analyze off-therapy outcomes following NA cessation in a large, international, multi-center, multi-ethnic cohort of chronic hepatitis B (CHB) patients.

Methods: This cohort study included virally suppressed CHB patients who were hepatitis B e antigen (HBeAg) negative and stopped NA therapy. Primary outcome was HBsAg loss after NA cessation, and secondary outcomes included virological, biochemical, and clinical relapse, ALT flare, retreatment, and liver-related events after NA cessation.

Results: Among 1,552 CHB patients, cumulative probability of HBsAg loss was 3.2% at 12 months and 13.0% at 48 months of follow-up. HBsAg loss was higher among Caucasians (vs. Asians: SHR 6.8; 95% CI 2.7-16.8; P < .001), and among patients with HBsAg levels <100 IU/mL at end of therapy (vs. ≥100 IU/mL: SHR 22.5; 95% CI 13.1-38.7; P < .001). At 48 months of follow-up, Caucasians with HBsAg levels <1000 IU/mL and Asians with HBsAg levels <100 IU/mL at end of therapy had a high predicted probability of HBsAg loss (>30%). Incidence rate of hepatic decompensation and hepatocellular carcinoma (HCC) was 0.48 per 1000 person-years and 0.29 per 1000 person-years, respectively. Death occurred in 7/19 decompensated patients and 2/14 patients with HCC.

Conclusion: The best candidates for NA withdrawal are virally suppressed, HBeAg negative, non-cirrhotic CHB patients with low HBsAg levels, particularly Caucasians with <1000 IU/mL and Asians with <100 IU/mL. However, strict surveillance is recommended to prevent deterioration.

Keywords: HBV; HBsAg seroconversion; antiviral; discontinuation.

Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.