Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
Department of Viroscience, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
J Infect Dis. 2022 Dec 28;227(1):113-122. doi: 10.1093/infdis/jiac210.
Emerging evidence suggests a pivotal role for B-cell responses in the natural history of chronic hepatitis B. Serum levels of antibodies to hepatitis B core antigen (anti-HBc) vary across infection stages, but their role in predicting response to antiviral therapy is uncertain.
Anti-HBc levels were assessed before peginterferon (PEG-IFN) therapy in patients with chronic hepatitis B who either started de novo PEG-IFN (n = 299; 195 hepatitis B e antigen [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 histological findings, and (3) treatment response.
We studied 390 patients. The hepatitis B virus (HBV) genotype were A, B, C, and D in 24%, 9%, 16%, and 49%, respectively; 72% of patients were Caucasian. Among currently untreated HBeAg-positive patients, anti-HBc was correlated with HBV DNA, hepatitis B core-related antigen (HBcrAg), hepatitis B surface antigen (HBsAg), and HBV RNA, but not with alanine aminotransferase (ALT). Higher anti-HBc was associated with more severe histological inflammatory activity (P < .001), irrespective of HBeAg status. After de novo PEG-IFN, higher anti-HBc levels were associated with HBeAg loss, sustained response, HBsAg decline, and HBsAg clearance (P < .050). Among patients treated with add-on PEG-IFN, higher anti-HBc was associated with HBeAg loss (P = .01).
Serum anti-HBc levels correlate with histological inflammatory activity. Higher anti-HBc levels were associated with favorable treatment outcomes. These findings suggest that anti-HBc could be used to select patients most likely to respond to immunomodulatory therapy.
NCT00114361, NCT00146705, NCT00877760, and NCT01532843.
新出现的证据表明 B 细胞反应在慢性乙型肝炎的自然史中起着关键作用。乙型肝炎核心抗原（抗-HBc）的血清水平在感染阶段有所不同，但它们在预测抗病毒治疗反应方面的作用尚不确定。
在开始使用聚乙二醇干扰素（PEG-IFN）治疗慢性乙型肝炎患者之前，评估了抗-HBc 水平，这些患者要么开始新的 PEG-IFN（n = 299；195 例 HBeAg 阳性），要么开始将 PEG-IFN 添加到现有的核苷（酸）类似物基础上（n = 91；均为 HBeAg 阳性）。研究了抗-HBc 与（1）血清生物标志物、（2）肝组织学发现和（3）治疗反应之间的关系。
我们研究了 390 名患者。乙型肝炎病毒（HBV）基因型分别为 A、B、C 和 D 的患者比例为 24%、9%、16%和 49%；72%的患者为白种人。在未接受治疗的 HBeAg 阳性患者中，抗-HBc 与 HBV DNA、乙型肝炎核心相关抗原（HBcrAg）、乙型肝炎表面抗原（HBsAg）和 HBV RNA 相关，但与丙氨酸氨基转移酶（ALT）无关。较高的抗-HBc 与更严重的组织学炎症活动相关（P <.001），与 HBeAg 状态无关。在开始新的 PEG-IFN 治疗后，较高的抗-HBc 水平与 HBeAg 丢失、持续反应、HBsAg 下降和 HBsAg 清除相关（P <.050）。在接受添加 PEG-IFN 治疗的患者中，较高的抗-HBc 与 HBeAg 丢失相关（P =.01）。
血清抗-HBc 水平与组织学炎症活动相关。较高的抗-HBc 水平与治疗结果良好相关。这些发现表明，抗-HBc 可用于选择最有可能对免疫调节治疗有反应的患者。
NCT00114361、NCT00146705、NCT00877760 和 NCT01532843。
