早期病毒学复发可预测慢性乙型肝炎患者停用核苷（酸）类

StephenW

早期病毒学复发可预测慢性乙型肝炎患者停用核苷（酸）类似物后的 ALT 发作
Kin Seng Liem 1 2，Heng Chi 2，Scott Fung 1，David K Wong 1，Colina Yim 1，Seham Noureldin 1，Jiayun Chen 1，Robert A de Man 2，Arif Sarowar 1，Jordan J Feld 1 3，Bettina E Hansen 1 2 4 , 侯金林 5 , 杰鹏 5 , 哈里·拉·詹森 1 2
隶属关系
隶属关系

    1
    多伦多肝病中心，大学健康网络，加拿大多伦多。
    2
    荷兰鹿特丹伊拉斯姆斯大学鹿特丹医学中心胃肠病学和肝病学系。
    3
    McLaughlin-Rotman 全球健康中心，加拿大多伦多。
    4
    加拿大多伦多大学卫生政策、管理和评估研究所。
    5
    广东省病毒性肝炎研究重点实验室，南方医科大学南方医院传染病科，广州，中国。

    PMID：36048970 DOI：10.1111/jvh.13742

抽象的

当慢性乙型肝炎 (CHB) 患者在实现 HBsAg 消失之前停止核苷（酸）类似物 (NA) 治疗时，通常会出现难以及早预测的发作。我们确定了停用 NA 后发作的发生率、严重程度、结果和预测因素。纳入随机对照试验的 45 名患者；来自外部前瞻性队列的 107 名患者用于验证。再治疗标准是预先定义的。通过 Cox 比例风险回归评估治疗前和治疗后 ALT 耀斑 (>5x ULN) 的预测因子。 NA 撤除 72 周后，23/45 (51%) 名患者出现 >5x ULN 和 14 (31%) >20x ULN。发生 ALT > 5x ULN 的中位时间是 NA 退出后 12 周。 ALT > 5x ULN 的独立预测因素是停药第 6 周时的男性（HR [95%CI] 3.2 [1.2-8.9]；p=0.03）和血清 HBV DNA（1.2 [1.0-1.8]；p=0.03） .具体而言，第 6 周 HBV DNA >10,000 IU/mL 预测 ALT >5x ULN (3.4 [1.4-8.4]; p=0.01)，这是经过外部验证的。总之，这项关于治疗后发作的研究揭示了慢性乙型肝炎的高累积发病率。第 6 周 HBV DNA >10,000 IU/mL 独立预测发作。所提出的阈值能够预测可能受益于更密切监测和早期再治疗的患者即将发生的发作。

关键词：停产；耀斑;核苷（酸）类似物；病毒性肝炎。

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StephenW

Early virologic relapse predicts ALT flares after nucleos(t)ide analogue withdrawal in patients with chronic hepatitis B
Kin Seng Liem  1   2 , Heng Chi  2 , Scott Fung  1 , David K Wong  1 , Colina Yim  1 , Seham Noureldin  1 , Jiayun Chen  1 , Robert A de Man  2 , Arif Sarowar  1 , Jordan J Feld  1   3 , Bettina E Hansen  1   2   4 , Jinlin Hou  5 , Jie Peng  5 , Harry L A Janssen  1   2
Affiliations
Affiliations

    1
    Toronto Centre for Liver Disease, University Health Network, Toronto, Canada.
    2
    Department of Gastroenterology and Hepatology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.
    3
    McLaughlin-Rotman Centre for Global Health, Toronto, Canada.
    4
    Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada.
    5
    Department of Infectious Diseases, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, China.

    PMID: 36048970 DOI: 10.1111/jvh.13742

Abstract

When patients with chronic hepatitis B (CHB) stop nucleos(t)ide analogue (NA) therapy before achieving HBsAg loss, flares often ensue which are challenging to predict early. We determined the incidence, severity, outcome and predictors of flares after NA withdrawal. Forty-five patients enrolled in an RCT were included; 107 patients from an external, prospective cohort were used for validation. Retreatment criteria were pre-defined. Pre- and post-treatment predictors of ALT flare (>5x ULN) were evaluated by Cox proportional-hazards regression. Seventy-two weeks after NA withdrawal, 23/45 (51%) patients had developed >5x ULN and 14 (31%) >20x ULN. Median time to develop ALT >5x ULN was 12 weeks after NA withdrawal. Independent predictors of ALT >5x ULN were male sex (HR [95%CI] 3.2 [1.2-8.9]; p=0.03) and serum HBV DNA (1.2 [1.0-1.8]; p=0.03) at week 6 off-therapy. Specifically, week 6 HBV DNA >10,000 IU/mL predicted ALT >5x ULN (3.4 [1.4-8.4]; p=0.01), which was externally validated. In conclusion, this study on post-treatment flares revealed a high cumulative incidence in CHB. Week 6 HBV DNA >10,000 IU/mL independently predicted flares. The proposed threshold enables prediction of imminent flares in patients who may benefit from closer monitoring and earlier retreatment.

Keywords: discontinuation; flares; nucleos(t)ide analogue; viral hepatitis.

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