Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
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.
J Viral Hepat. 2019 Jul;26 Suppl 1:59-68. doi: 10.1111/jvh.13153.
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.
虽然核苷（酸）类似物（NA）单药治疗可有效抑制乙型肝炎病毒（HBV）并逆转肝纤维化，但血清学应答率并不理想。评估 NA 和聚乙二醇干扰素 α（PegIFNα）联合治疗慢性乙型肝炎（CHB）患者的获益的研究结果相互矛盾，主要集中在血清学结局上。NA-PegIFNα 联合治疗的组织学应答变化尚未在真实世界的实践中得到评估。本研究旨在评估 CHB 患者接受 NA-PegIFNα 联合治疗后的组织学变化，并全面比较 NA-PegIFNα 联合治疗与 NA 单药治疗的疗效。我们对接受 NA-PegIFNα 联合治疗或 NA 单药治疗的 40 例 CHB 患者的数据进行了回顾性分析。评估治疗开始后 48 周时的组织学变化。还分析了血清学特征，并比较了 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的差异。与基线活检相比，两组患者的纤维化分期和坏死性炎症评分在治疗后第二次活检时均显著降低。几乎所有患者的炎症均得到缓解（两组均为 87.5%），但有一小部分患者的炎症无明显改善或纤维化进展（NA 单药治疗组和 NA-PegIFNα 联合治疗组分别为 33.3%和 31.2%）。抗病毒治疗 48 周后，几乎所有患者的 ALT 恢复正常并获得持续病毒学应答（SVR）。治疗开始后 48 周时，约有三分之一的个体（两组分别为 36.8%和 30%）实现了 HBeAg 丢失。尽管两组的组织学、生化、病毒学和血清学应答的总体发生率无显著差异，但在 NA-PegIFNα 联合治疗组患者的长期随访中，观察到更早的病毒学应答和更高的累积 SVR 率（P=0.0129）。在长期随访中，还观察到 HBeAg 丢失更快和累积 HBeAg 丢失率更高的趋势，但无统计学意义。治疗开始后 24 周和 48 周时的 ALT 正常化率与组织学应答相关。NA-PegIFNα 联合治疗或 NA 单药治疗均能显著减轻肝纤维化和缓解坏死性炎症。两组均观察到显著的生化、病毒学和血清学应答，两组在 48 周时的应答率相似。在长期随访期间，联合治疗方案的病毒学和血清学应答更快且更优。
