Histological response to combination therapy with nucleos(t)ide analogs and peginterferon alpha in treatment-naive chronic hepatitis B patients
Histological response to combination therapy with nucleos(t)ide analogs and peginterferon alpha in treatment-naive chronic hepatitis B patients
复制标题
初治慢性乙型肝炎患者对核苷（酸）类似物和聚乙二醇干扰素α联合治疗的组织学反应
DOI：
10.1111/jvh.13153
复制
发表时间：
2019
影响因子：
2.5
通讯作者：
Zhang Wenhong
中科院分区：
文献类型：
--
作者：
Zhang Qiran;Li Guojun;Yu Yiqi;Qiu Chao;Zheng Jianming;Zhang Hanyue;Zhang Miaoqu;Song Zhangzhang;Yang Yusheng;Du Xinfang;Hong Jiemin;Lu Jian;Li Niuniu;Tang Quanzhen;Xu Long;Wang Xuanyi;Huang Yuxian;Zhang Jiming;Chen Zhi;Zhang Wenhong
尽管核苷（酸）类似物（NA）单药治疗在抑制B型肝炎病毒和纤维化消退方面有效，但血清学应答率并不令人满意。评估NAs和聚乙二醇干扰素α（PegIFNα）联合治疗慢性B型肝炎（CH B）患者的获益的研究产生了相互矛盾的结果，主要集中在血清学结局上。尚未在真实的实践中评价联合治疗后的组织学变化。本研究旨在评价CHB患者对NA‐PegIFNα联合治疗的组织学变化，并全面比较NA‐PegIFNα联合治疗与NA单药治疗的疗效。我们对40例接受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。评价治疗开始后48周的组织学变化。还分析了血清学特征，并在NA‐PegIFNα联合治疗组和NA单药治疗组之间以及组织学应答者和非应答者之间进行了比较。与基线活检相比，两组治疗后检查的第二次活检的纤维化分期和坏死性炎症分级评分均显著降低。几乎所有患者的炎症减轻（两组均为87.5%），但有一个亚组的患者未表现出显著改善或纤维化进展（NA单药治疗组和NA‐PegIFNα联合治疗组分别为33.3%和31.2%）。几乎所有患者在48周的抗病毒治疗后都实现了ALT正常化和持续病毒学应答（SVR）。大约三分之一的个体（两组分别为36.8%和30%）在治疗开始后48周达到HBeAg下降。尽管两组之间的组织学、生化、病毒学和血清学应答的总体发生率无显著差异，但在长期随访期间，在接受NA-PegIFNα联合治疗的患者中观察到较早的病毒学应答和随时间推移较高的累积SVR率（P= 0. 0129）。在长期随访期间，也观察到HBeAg丢失更快和累积HBeAg丢失率更高的趋势，但无统计学显著性。治疗开始后24周和48周的ALT正常化率与组织学反应相关。NA-PegIFN α联合治疗或NA单药治疗诱导纤维化显著消退和坏死性炎症消退。两组均观察到显著的生化、病毒学和血清学应答，48周时两组的应答率相似。在长期随访期间，随着时间的推移，联合治疗方案后的病毒学和血清学应答更快且上级。
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.