Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong.
Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan.
J Gastroenterol Hepatol. 2020 Dec;35(12):2202-2209. doi: 10.1111/jgh.15058. Epub 2020 May 1.
Hepatitis B core-related antigen (HBcrAg) has been shown to correlate with various viral markers in chronic hepatitis B, but its role in defining natural history is not well studied. We aimed to investigate the use of HBcrAg to define different phases of chronic hepatitis B.
Stored residual serum samples from longitudinal cohorts of chronic hepatitis B patients in Hong Kong and Japan were studied. Viral markers were measured in three serial serum samples for each patient. Patients were divided into six groups for analysis: hepatitis B e antigen (HBeAg)-positive chronic infection (EPI), HBeAg-positive chronic hepatitis (EPH), HBeAg seroconversion (ES), HBeAg-negative chronic hepatitis (ENH), HBeAg-negative chronic infection (ENI), and HBsAg seroclearance (SS).
In total, 166 patients followed up for 100 (76-113) months were included. HBcrAg was correlated with hepatitis B virus DNA and HBsAg levels in both HBeAg-positive and HBeAg-negative patients. HBcrAg cut-off of ≥ 6.0 log U/mL could best differentiate HBeAg-positive from HBeAg-negative patients (area under receiver operating characteristic curve of 0.99, P < 0.001). HBcrAg could not differentiate patients in EPI and EPH phases, but HBcrAg declined dramatically at HBeAg seroconversion. In HBeAg-negative patients, HBcrAg ≥ 4.0 log U/mL could best differentiate ENH from ENI (area under receiver operating characteristic curve of 0.81; P < 0.001), with high specificity (81.6%) but only moderate sensitivity (65.7%) at baseline. Undetectable HBcrAg was found in 17%, 63%, and 89% patients in ENH, ENI, and SS groups at the last visit, respectively.
HBcrAg provides useful information to stage the natural history of chronic hepatitis B, particularly identifying HBeAg-positive patients and HBeAg-negative patients with active disease.
乙型肝炎核心相关抗原（HBcrAg）已被证明与慢性乙型肝炎的各种病毒标志物相关，但它在定义自然史中的作用尚未得到充分研究。本研究旨在探讨使用 HBcrAg 来定义慢性乙型肝炎的不同阶段。
研究了来自香港和日本慢性乙型肝炎患者纵向队列的储存剩余血清样本。对每位患者的三份连续血清样本进行病毒标志物检测。将患者分为六组进行分析：乙型肝炎 e 抗原（HBeAg）阳性慢性感染（EPI）、HBeAg 阳性慢性肝炎（EPH）、HBeAg 血清学转换（ES）、HBeAg 阴性慢性肝炎（ENH）、HBeAg 阴性慢性感染（ENI）和 HBsAg 血清学清除（SS）。
共纳入 166 例患者，随访 100（76-113）个月。HBcrAg 与 HBeAg 阳性和 HBeAg 阴性患者的乙型肝炎病毒 DNA 和 HBsAg 水平相关。HBcrAg 截断值≥6.0 log U/mL 可最好地区分 HBeAg 阳性和 HBeAg 阴性患者（ROC 曲线下面积为 0.99，P<0.001）。HBcrAg 不能区分 EPI 和 EPH 期患者，但 HBeAg 血清学转换时 HBcrAg 显著下降。在 HBeAg 阴性患者中，HBcrAg≥4.0 log U/mL 可最好地区分 ENH 和 ENI（ROC 曲线下面积为 0.81；P<0.001），基线时具有高特异性（81.6%）但仅中等敏感性（65.7%）。在最后一次就诊时，ENH、ENI 和 SS 组分别有 17%、63%和 89%的患者 HBcrAg 不可检测。
HBcrAg 提供了有用的信息来分期慢性乙型肝炎的自然史，特别是识别 HBeAg 阳性患者和具有活动性疾病的 HBeAg 阴性患者。
