Objective Selected populations of patients with chronic hepatitis B (CHB) may benefit from a combined use of pegylated interferon-alpha (pegIFN-α) and nucleos(t)ides (NUCs). The aim of our study was to assess the immunomodulatory effect of pegIFN-α on T and natural killer (NK) cell responses in NUC-suppressed patients to identify cellular and/or serological parameters to predict better T cell-restoring effect and better control of infection in response to pegIFN-α for a tailored application of IFN-α add-on. Design 53 HBeAg-negative NUC-treated patients with CHB were randomised at a 1:1 ratio to receive pegIFN-α-2a for 48 weeks, or to continue NUC therapy and then followed up for at least 6 months maintaining NUCs. Serum hepatitis B surface antigen (HBsAg) and hepatitis B core‐related antigen (HBcrAg) levels as well as peripheral blood NK cell phenotype and function and HBV-specific T cell responses upon in vitro stimulation with overlapping HBV peptides were measured longitudinally before, during and after pegIFN-α therapy. Results Two cohorts of pegIFN-α treated patients were identified according to HBsAg decline greater or less than 0.5 log at week 24 post-treatment. PegIFN-α add-on did not significantly improve HBV-specific T cell responses during therapy but elicited a significant multispecific and polyfunctional T cell improvement at week 24 post-pegIFN-α treatment compared with baseline. This improvement was maximal in patients who had a higher drop in serum HBsAg levels and a lower basal HBcrAg values. Conclusions PegIFN-α treatment can induce greater functional T cell improvement and HBsAg decline in patients with lower baseline HBcrAg levels. Thus, HBcrAg may represent an easily and reliably applicable parameter to select patients who are more likely to achieve better response to pegIFN-α add-on to virally suppressed patients. All data relevant to the study are included in the article or uploaded as supplemental information.

中文翻译：

---

HBcrAg 值可预测 NUC 抑制的 HBeAg 阴性慢性乙型肝炎患者对 pegIFN-α 的病毒学和免疫学反应


目的 特定的慢性乙型肝炎 (CHB) 患者人群可能会受益于聚乙二醇化干扰素-α (pegIFN-α) 和核苷（酸）苷 (NUC) 的联合使用。我们研究的目的是评估 pegIFN-α 对 NUC 抑制患者的 T 细胞和自然杀伤 (NK) 细胞反应的免疫调节作用，以确定细胞和/或血清学参数，从而预测更好的 T 细胞恢复效果和更好的控制感染对 pegIFN-α 的反应，以定制 IFN-α 附加应用。设计 53 名 HBeAg 阴性 NUC 治疗的 CHB 患者以 1:1 的比例随机接受 pegIFN-α-2a 治疗 48 周，或继续 NUC 治疗，然后随访至少 6 个月，维持 NUC。在使用重叠 HBV 肽体外刺激后，纵向测量血清乙型肝炎表面抗原 (HBsAg) 和乙型肝炎核心相关抗原 (HBcrAg) 水平以及外周血 NK 细胞表型和功能以及 HBV 特异性 T 细胞反应。以及pegIFN-α治疗后。结果 根据治疗后第 24 周 HBsAg 下降大于或小于 0.5 log 来确定两组接受 pegIFN-α 治疗的患者。 PegIFN-α附加疗法在治疗期间并未显着改善HBV特异性T细胞反应，但与基线相比，在pegIFN-α治疗后第24周引起了显着的多特异性和多功能T细胞改善。这种改善在血清 HBsAg 水平下降较多且基础 HBcrAg 值较低的患者中最为明显。结论 PegIFN-α 治疗可以在基线 HBcrAg 水平较低的患者中诱导更大的功能性 T 细胞改善和 HBsAg 下降。 因此，HBcrAg 可能是一个简单且可靠的适用参数，适用于选择更有可能对病毒抑制患者添加 pegIFN-α 产生更好反应的患者。与研究相关的所有数据都包含在文章中或作为补充信息上传。