抗 HBc 水平与慢性乙型肝炎患者的肝脏炎症和对聚乙二醇干扰

StephenW

抗 HBc 水平与慢性乙型肝炎患者的肝脏炎症和对聚乙二醇干扰素的反应有关
Sylvia M Brakenhoff 1 ，Robert J de Knegt 1 ，Jeffrey Oliveira 1 ，Annemiek A van der Eijk 2 ，Anneke J van Vuuren 1 ，Bettina E Hansen 3 4 ，Harry L A Janssen 3 ，Robert A de Man 1 ，André Boonstra 1 ，米兰Ĵ桑内维尔德 1
隶属关系
隶属关系

    1
    荷兰鹿特丹大学医学中心 Erasmus MC 胃肠病学和肝病学系。
    2
    荷兰鹿特丹大学医学中心 Erasmus MC 病毒科学系。
    3
    多伦多肝病中心，多伦多西部和综合医院，大学健康网络，加拿大多伦多。
    4
    加拿大多伦多大学卫生政策、管理和评估研究所。

    PMID：35599306 DOI：10.1093/infdis/jiac210

抽象的

背景：新出现的证据表明，B 细胞反应在慢性乙型肝炎 (CHB) 的自然病程中起着关键作用。 HBcAg（抗-HBc）的血清抗体水平因感染阶段而异，但它们在预测抗病毒治疗反应中的作用尚不确定。

方法：在聚乙二醇干扰素 (PEG-IFN) 治疗之前评估抗 HBc 水平，这些患者要么从头开始 PEG-IFN（n = 299；195 HBeAg 阳性），要么开始将 PEG-IFN 作为现有药物的附加物。核（s）潮类似物骨架（n = 91，所有 HBeAg 阳性）。探讨了抗 HBc 与 (1) 血清生物标志物、(2) 肝脏组织学和 (3) 治疗反应之间的关联。

结果：我们研究了 390 名患者。 HBV 基因型在 24/9/16/49% 中为 A/B/C/D，72% 为高加索人。在目前未经治疗的 HBeAg 阳性患者中，抗 HBc 与 HBV DNA、HBcrAg、HBsAg 和 HBV RNA 相关，但与 ALT 无关。与 HBeAg 状态无关，较高的抗 HBc 与更严重的组织学炎症活动相关（p < 0.001）。从头 PEG-IFN 后，较高的抗 HBc 与 HBeAg 消失、持续反应、HBsAg 下降和 HBsAg 清除相关（p < 0.050）。在接受附加 PEG-IFN 治疗的患者中，较高的抗 HBc 与 HBeAg 消失相关（p = 0.012）。

结论：血清抗 HBc 水平与组织学炎症活动相关。较高的抗 HBc 水平与良好的治疗结果相关。这些发现表明，抗 HBc 可用于选择最有可能对免疫调节治疗产生反应的患者。

关键词：B细胞；乙型肝炎；血清生物标志物；抗-HBc；肝脏炎症。

StephenW

Anti-HBc levels are associated with liver inflammation and response to peginterferon in chronic hepatitis B patients
Sylvia M Brakenhoff  1 , Robert J de Knegt  1 , Jeffrey Oliveira  1 , Annemiek A van der Eijk  2 , Anneke J van Vuuren  1 , Bettina E Hansen  3   4 , Harry L A Janssen  3 , Robert A de Man  1 , André Boonstra  1 , Milan J Sonneveld  1
Affiliations
Affiliations

    1
    Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
    2
    Department of Viroscience, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
    3
    Toronto Center for Liver Disease, Toronto Western and General Hospital, University Health Network, Toronto, Canada.
    4
    Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada.

    PMID: 35599306 DOI: 10.1093/infdis/jiac210

Abstract

Background: Emerging evidence suggests a pivotal role for B-cell responses in the natural history of chronic hepatitis B (CHB). Serum levels of antibodies to HBcAg (anti-HBc) vary across infection stages, but their role in predicting response to antiviral therapy is uncertain.

Methods: Anti-HBc levels were assessed before peginterferon (PEG-IFN) therapy in CHB patients who either initiated de novo PEG-IFN (n = 299; 195 HBeAg-positive), or started PEG-IFN as add-on to an existing nucleo(s)tide analogue backbone (n = 91, all HBeAg-positive). Associations were explored between anti-HBc and (1)serum biomarkers, (2)liver histology and (3)treatment response.

Results: We studied 390 patients. HBV-genotypes were A/B/C/D in 24/9/16/49%, and 72% were Caucasian. Among currently untreated HBeAg-positive patients, anti-HBc correlated with HBV DNA, HBcrAg, HBsAg and HBV RNA, but not with ALT. Higher anti-HBc was associated with more severe histological inflammatory activity (p < 0.001), irrespective of HBeAg-status. After de novo PEG-IFN, higher anti-HBc was associated with HBeAg-loss, sustained response, HBsAg-decline and HBsAg-clearance (p < 0.050). Among patients treated with add-on PEG-IFN, higher anti-HBc was associated with HBeAg-loss (p = 0.012).

Conclusions: Serum anti-HBc levels correlate with histological inflammatory activity. Higher anti-HBc levels were associated with favourable treatment outcomes. These findings suggest that anti-HBc could be used to select patients most likely to respond to immunomodulatory-therapy.

Keywords: B cell; Hepatitis B; Serum biomarkers; anti-HBc; liver inflammation.