jvh.13153。 对未治疗的慢性乙型肝炎患者的核苷（t）ide类似物

StephenW

J Viral Hepat. 2019 Jul;26 Suppl 1:59-68. doi: 10.1111/jvh.13153.
Histological response to combination therapy with nucleos(t)ide analogs and peginterferon alpha in treatment-naïve chronic hepatitis B patients.
Zhang Q1, Li G2,3, Yu Y1, Qiu C1,4, Zheng J1, Zhang H1, Zhang M1, Song Z5, Yang Y5, Du X6, Hong J3, Lu J3, Li N3, Tang Q3, Xu L3, Wang X4, Huang Y1, Zhang J1,5, Chen Z2, Zhang W1,4.
Author information

1
    Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
2
    State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
3
    Department of Infectious Diseases, Shenzhen University General Hospital, Shenzhen, China.
4
    Institutes of Biomedical Sciences and Key Laboratory of Medical Molecular Virology, Fudan University, Shanghai, China.
5
    Department of Hepatology, The Second Hospital of Yinzhou of Ningbo, Ningbo, China.
6
    Department of Hepatology, Beilun People's Hospital, Ningbo, China.

Abstract

Although nucleos(t)ide analog (NA) monotherapy is effective in hepatitis B virus suppression and fibrosis regression, serological response rates are not satisfactory. Studies assessing the benefits of combination therapy with NAs and peginterferon alpha (PegIFNα) in patients with chronic hepatitis B (CHB) have produced conflicting results and mainly focused on serological outcomes. Histological changes in response to combination therapy have not been evaluated in real-world practice. This study aimed to evaluate the histological changes in response to NA-PegIFNα combination therapy in CHB patients and to comprehensively compare the efficacy of NA-PegIFNα combination therapy and NA monotherapy. We conducted a retrospective analysis of data from 40 CHB patients who underwent either NA-PegIFNα combination therapy or NA monotherapy. Changes in histology at 48 weeks after treatment initiation were evaluated. Serological characteristics were also analysed and compared between the NA-PegIFNα combination therapy and NA monotherapy groups and between histological responders and nonresponders. Compared to baseline biopsies, both fibrosis staging and necroinflammatory grading scores were significantly lower in the second biopsies examined post-treatment in both groups. Nearly all patients experienced a reduction in inflammation (87.5% in both groups), but there was a subgroup of patients who exhibited either no significant improvement or fibrosis progression (33.3% and 31.2% in the NA monotherapy and NA-PegIFNα combination therapy groups, respectively). Nearly, all patients achieved ALT normalization and sustained virological response (SVR) after 48 weeks of antiviral treatment. Approximately one-third of individuals (36.8% and 30% in the two groups, respectively) achieved HBeAg loss at 48 weeks after treatment initiation. Although there were no significant differences in overall rates of histological, biochemical, virological and serological responses between the two groups, an earlier virological response and a higher cumulative SVR rate over time were observed during long-term follow-up in patients treated with NA-PegIFNα combination therapy (P = 0.0129). Trends of more rapid HBeAg loss and a higher cumulative HBeAg loss rate throughout long-term follow-up were also observed but were not statistically significant. The ALT normalization rates at 24 and 48 weeks after treatment initiation were associated with the histological response. Significant regression of fibrosis and resolution of necroinflammation were induced with either NA-PegIFNα combination therapy or NA monotherapy. Significant biochemical, virological and serological responses were observed in both groups, and the response rates at 48 weeks were similar in the two groups. Over time during long-term follow-up, the virological and serological responses were faster and superior following the combination regimen.

© 2019 John Wiley & Sons Ltd.
KEYWORDS:

chronic hepatitis B; histopathology; nucleos(t)ide analogs; peginterferon

PMID:
    31380588
DOI:
    10.1111/jvh.13153

StephenW

J病毒肝病。 2019年7月; 26增刊1：59-68。 doi：10.1111 / jvh.13153。
对未治疗的慢性乙型肝炎患者的核苷（t）ide类似物和聚乙二醇干扰素α联合治疗的组织学反应。
Zhang Q1，Li G2,3，Yu Y1，Qiu C1,4，Zheng J1，Zhang H1，Zhang M1，Song Z5，Yang Y5，Du X6，Hong J3，Lu J3，Li N3，Tang Q3，Xu L3，Wang X4，黄Y1，张J1,5，陈Z2，张W1,4。
作者信息

1
    复旦大学附属华山医院感染科，上海
2
    浙江大学医学院附属第一医院传染病诊断与治疗协同创新中心国家重点实验室，杭州，中国。
3
    深圳大学总医院传染病科，深圳
4
    复旦大学生物医学科学研究所和医学分子病毒学重点实验室，上海
五
    宁波市鄞州区第二医院肝病科，宁波
6
    中国宁波市北仑人民医院肝病科

抽象

尽管核苷（酸）类似物（NA）单一疗法在乙型肝炎病毒抑制和纤维化消退中是有效的，但血清学应答率并不令人满意。评估慢性乙型肝炎（CHB）患者使用NAs和聚乙二醇干扰素α（PegIFNα）联合治疗的益处的研究产生了相互矛盾的结果，主要集中在血清学结果上。在实际操作中尚未评估对组合疗法的组织学变化。本研究旨在评估CHB患者NA-PegIFNα联合治疗的组织学变化，并综合比较NA-PegIFNα联合治疗与NA单药治疗的疗效。我们对40名接受NA-PegIFNα联合治疗或NA单药治疗的CHB患者的数据进行了回顾性分析。评估治疗开始后48周的组织学变化。还分析了NA-PegIFNα组合疗法和NA单一疗法组之间以及组织学应答者和无应答者之间的血清学特征。与基线活组织检查相比，两组患者在治疗后检查的第二次活组织检查中纤维化分期和坏死性炎症分级评分均显着降低。几乎所有患者均出现炎症减轻（两组均为87.5％），但有一组患者无明显改善或纤维化进展（NA单药治疗和NA-PegIFNα联合治疗组为33.3％和31.2％，分别）。几乎所有患者在抗病毒治疗48周后均达到ALT正常化和持续病毒学应答（SVR）。大约三分之一的个体（分别为36.8％和30％）在治疗开始后48周达到HBeAg消失。尽管两组之间的组织学，生物化学，病毒学和血清学反应总体发生率没有显着差异，但在NA-治疗的患者长期随访期间观察到较早的病毒学应答和较高的累积SVR率。 PegIFNα联合治疗（P = 0.0129）。在整个长期随访中观察到更快的HBeAg消失和更高的累积HBeAg丢失率的趋势，但没有统计学意义。治疗开始后24和48周的ALT正常化率与组织学反应相关。用NA-PegIFNα组合疗法或NA单一疗法诱导纤维化的显着消退和坏死性炎症的消退。两组均观察到显着的生化，病毒学和血清学反应，两组的48周反应率相似。随着时间的推移，在长期随访期间，组合方案后病毒学和血清学反应更快，更优越。

©2019 John Wiley＆Sons Ltd.
关键词：

慢性乙型肝炎;组织病理学;核苷（酸）类似物;聚乙二醇干扰素

结论：
    31380588
DOI：
    10.1111 / jvh.13153