慢性乙型肝炎病毒学应答延长后停止抗病毒治疗的前瞻性研

StephenW

慢性乙型肝炎病毒学应答延长后停止抗病毒治疗的前瞻性研究Naveen Gara #1, Michele M Tana #2, Meera Kattapuram 3, Sungyoung Auh 4, Lauren Sullivan 3, Nancy Fryzek 3, Mary Walter 4, Regina Umarova 3, Xiongce Zhao 5, Gavin Cloherty 6, Edward H. , T 杰克梁 3 , 马克 G 加尼 3隶属关系隶属关系    1    美国加利福尼亚州埃斯孔迪多胃肠病学和肝脏研究所。    2    加利福尼亚大学旧金山医学院，美国加利福尼亚州旧金山。    3    美国国立卫生研究院国家糖尿病、消化和肾脏疾病研究所肝脏疾病分部，贝塞斯达，马里兰州，美国。    4    临床核心，国家糖尿病、消化和肾脏疾病研究所，美国国立卫生研究院，贝塞斯达，马里兰州，美国。    5    美国国立卫生研究院糖尿病、消化和肾脏疾病研究所主任办公室，贝塞斯达，马里兰州，美国。    6    雅培诊断，雅培公园，伊利诺伊州，美国。#同等贡献。    PMID：34558806 DOI：10.1002/hep4.1761抽象的慢性乙型肝炎 (CHB) 的核苷类似物 (NA) 治疗与改善临床结果相关，但通常需要长期使用。治疗是否可以安全退出以及与退出后结果相关的因素尚不明确。为了评估停止抗病毒治疗后的长期结局，前瞻性研究了接受抗病毒治疗 4 年或以上且乙型肝炎病毒 (HBV) DNA (≤100 IU/mL) 的乙型肝炎 e 抗原 (HBeAg) 阴性 CHB 患者停止抗病毒治疗并在最初的 6 个月内每月监测一次，之后每 3 个月监测一次。临床复发者根据复发的严重程度进行再治疗。 15 名患者在平均治疗持续时间为 8.4 年后退出拉米夫定 (4)、阿德福韦 (5) 或两者的组合 (6)。平均年龄为 45 岁，13 人为男性，8 人在治疗前最初为 HBeAg 阳性。经过平均 6.6 年的随访，结果因治疗前 HBeAg 状态而异。所有治疗前为 HBeAg+ 的患者均出现病毒学复发（8 名中的 8 名）； 8 人中有 6 人经历了临床复发； 8 人中有 4 人有 ALT 耀斑； 8 人中有 5 人需要重新开始治疗，其中 1 人清除了乙型肝炎表面抗原 (HBsAg)； 8 人中有 3 人未接受治疗，其中 1 人清除了 HBsAg。相比之下，治疗前 HBeAg 阴性的 7 名患者中有 4 名出现病毒学复发，7 名患者中有 3 名出现临床复发，7 名患者中有 1 名出现丙氨酸转氨酶 (ALT) 发作。没有人重新开始治疗，7 人中有 4 人清除了 HBsAg。戒断前 HBsAg 水平低是 HBsAg 消失的预测因素。结论：大多数无肝硬化的 HBeAg 阴性患者可以安全地停止 NA 治疗，长期缓解且 HBsAg 消失率高。最初为 HBeAg+ 的患者不应停止治疗，因为临床复发频繁且通常很严重。© 2021 作者。由 Wiley Periodicals LLC 代表美国肝病研究协会出版的 Hepatology Communications。

StephenW

Prospective Study of Withdrawal of Antiviral therapy in Patients with Chronic Hepatitis B after Prolonged Virological Response
Naveen Gara #  1 , Michele M Tana #  2 , Meera Kattapuram  3 , Sungyoung Auh  4 , Lauren Sullivan  3 , Nancy Fryzek  3 , Mary Walter  4 , Regina Umarova  3 , Xiongce Zhao  5 , Gavin Cloherty  6 , Edward Doo  3 , Theo Heller  3 , T Jake Liang  3 , Marc G Ghany  3
Affiliations
Affiliations

    1
    Gastroenterology & Liver Institute, Escondido, CA, USA.
    2
    University of California San Francisco School of Medicine, San Francisco, CA, USA.
    3
    Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
    4
    Clinical Core, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
    5
    Office of the Director, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
    6
    Abbott Diagnostics, Abbott Park, IL, USA.

#
Contributed equally.

    PMID: 34558806 DOI: 10.1002/hep4.1761

Abstract

Nucleoside analogue (NA) therapy for chronic hepatitis B (CHB) is associated with improved clinical outcomes, but usually requires long-term use. Whether treatment can be safely withdrawn and the factors associated with post-withdrawal outcome are not well defined. To assess long-term outcomes after stopping antiviral therapy, patients with hepatitis B e antigen (HBeAg)-negative CHB who had received antiviral therapy for 4 or more years with hepatitis B virus (HBV) DNA (≤100 IU/mL) were prospectively withdrawn from antiviral therapy and monitored monthly for the initial 6 months and every 3 months thereafter. Those with clinical relapse were retreated according to severity of relapse. Fifteen patients were withdrawn from lamivudine (4), adefovir (5), or a combination of the two (6) after a mean treatment duration of 8.4 years. The mean age was 45 years, 13 were male, and 8 were initially HBeAg-positive before treatment. After a mean follow-up of 6.6 years, outcomes differed by pretreatment HBeAg status. All patients who were HBeAg+ before treatment experienced virological relapse (8 of 8); 6 of 8 experienced clinical relapse; 4 of 8 had ALT flares; 5 of 8 required re-initiation of treatment, one of whom cleared hepatitis B surface antigen (HBsAg); and 3 of 8 remained off treatment, one of whom cleared HBsAg. In contrast, 4 of 7 patients who were HBeAg-negative before treatment experienced virological relapse, 3 of 7 experienced clinical relapse, and 1 of 7 had an alanine aminotransferase (ALT) flare. None restarted treatment, and 4 of 7 cleared HBsAg. Low pre-withdrawal HBsAg level was predictive of HBsAg loss. Conclusion: NA therapy can be safely withdrawn with long-term remission and high rates of HBsAg loss in most HBeAg-negative patients without cirrhosis. Patients who were initially HBeAg+ should not be withdrawn from treatment, because clinical relapse was frequent and often severe.

© 2021 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of the American Association for the Study of Liver Diseases.

StephenW

https://aasldpubs.onlinelibrary. ... t/10.1002/hep4.1761