干扰素-α治疗HBeAg阳性慢性乙型肝炎病毒感染的超长期随访

StephenW

Ultra long-term follow-up of interferon-alpha treatment for HBeAg-positive chronic hepatitis B virus infection
Hannah S J Choi  1 , Margo J H van Campenhout  2 , Anneke J van Vuuren  2 , Lisette A P Krassenburg  3 , Milan J Sonneveld  2 , Robert J de Knegt  2 , Bettina E Hansen  4 , Harry L A Janssen  5
Affiliations
Affiliations

    1
    Toronto Centre for Liver Disease, University Health Network, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
    2
    Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands.
    3
    Toronto Centre for Liver Disease, University Health Network, Toronto, ON, Canada; Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands.
    4
    Toronto Centre for Liver Disease, University Health Network, Toronto, ON, Canada; Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.
    5
    Toronto Centre for Liver Disease, University Health Network, Toronto, ON, Canada. Electronic address: [email protected].

    PMID: 32890755 DOI: 10.1016/j.cgh.2020.09.004

Abstract

Background and aims: Interferon-alpha (IFN-α) treatment for chronic hepatitis B (CHB) virus infection is finite and leads to relatively higher functional cure rates (HBsAg loss) than nucleo(s)tide analogue (NA) therapy. Effects of pegylated (PEG)/conventional IFN-α treatment on clinical outcomes were evaluated in an ultra long-term follow-up of CHB patients.

Methods: HBeAg-positive patients treated with (PEG)IFN-α at a tertiary referral centre between 1977-2014 were included. We reviewed medical charts and consulted the municipal registry for patient information. Patients were invited for a single visit at the outpatient clinic in the case of missing follow-up data. The endpoints included serum HBeAg/HBsAg loss and incidence of clinical events, using life table methods and person-years to analyze the incidence of events. Patients were censored upon retreatment.

Results: The study cohort included 267 patients, 67% male, 58% Caucasian, with a median age of 32 years. The median follow-up duration was 11.5 years. The 5 and 10-year cumulative incidence of HBsAg loss were 14% and 32%, respectively. Baseline factors associated with a higher rate of HBsAg loss were male sex, Caucasian race, genotype A, age ≥40 years, and cirrhosis. HBsAg loss rates did not differ significantly between those who received short-term (≤24 weeks) versus long-term (>24 weeks) therapy. Both HBeAg and HBsAg loss were significantly associated with improved clinical outcomes. Early response (HBeAg loss) was associated with more HBsAg loss and better patient outcomes.

Conclusions: During long-term follow-up, high rates of HBsAg loss were observed from a single (PEG)IFN-α course. Its persistent effects suggest that a role for IFN-α remains, potentially in novel combination therapies in search of a functional cure.

Keywords: immunomodulator; long-term outcomes; prognosis; viral hepatitis.

Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.

StephenW

干扰素-α治疗HBeAg阳性慢性乙型肝炎病毒感染的超长期随访
Hannah S J Choi 1，Margo J H van Campenhout 2，Anneke J van Vuuren 2，Lisette A P Krassenburg 3，Milan J Sonneveld 2，Robert J de Knegt 2，Bettina E Hansen 4，Harry L A Janssen 5
隶属关系
隶属关系

    1个
    加拿大安大略省多伦多大学健康网络多伦多肝病中心；加拿大安大略省多伦多市多伦多大学医学科学研究所。
    2
    荷兰鹿特丹伊拉斯姆斯大学医学中心胃肠病学和肝病学。
    3
    加拿大安大略省多伦多大学健康网络多伦多肝病中心；荷兰鹿特丹伊拉斯姆斯大学医学中心胃肠病学和肝病学。
    4
    加拿大安大略省多伦多大学健康网络多伦多肝病中心；荷兰鹿特丹伊拉斯姆斯大学医学中心胃肠病学和肝病学；加拿大安大略省多伦多市多伦多大学卫生政策，管理与评估研究所。
    5
    多伦多肝病中心，大学健康网络，多伦多，加拿大。电子地址：[email protected]。

    PMID：32890755 DOI：10.1016 / j.cgh.2020.09.004

抽象

背景与目的：干扰素-α（IFN-α）治疗慢性乙型肝炎（CHB）病毒的治疗是有限的，并且与核苷酸类似物（NA）治疗相比，可导致相对较高的功能治愈率（HBsAg损失）。在CHB患者的超长期随访中评估了聚乙二醇化（PEG）/常规IFN-α治疗对临床结局的影响。

方法：纳入1977-2014年间在三级转诊中心接受（PEG）IFN-α治疗的HBeAg阳性患者。我们检查了病历，并咨询了市政府有关患者的信息。如果缺少随访数据，则邀请患者在门诊就诊。终点包括血清HBeAg / HBsAg丢失和临床事件发生率，使用生命表方法和人年分析事件发生率。复诊后对患者进行检查。

结果：该研究队列包括267位患者，其中男性67％，白种人58％，中位年龄为32岁。中位随访时间为11。5年。 HBsAg丢失的5年和10年累积发生率分别为14％和32％。与HBsAg丢失率更高相关的基线因素是男性，白种人，基因型A，年龄≥40岁和肝硬化。接受短期（≤24周）治疗与长期（> 24周）治疗者之间的HBsAg丢失率无显着差异。 HBeAg和HBsAg的丢失均与改善临床结局密切相关。早期反应（HBeAg丢失）与更多的HBsAg丢失和更好的患者预后相关。

结论：在长期随访中，单次（PEG）IFN-α疗程观察到HBsAg丢失率高。它的持续作用表明，IFN-α的作用仍然存在，可能在寻求功能治愈的新型联合疗法中。

关键字：免疫调节剂；长期结果；预后病毒性肝炎。

版权所有©2020 AGA Institute。由Elsevier Inc.出版。保留所有权利。

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