Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing 100034, China.
The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, Zhejiang 310000, China.
Chin Med J (Engl). 2021 Mar 17;134(10):1160-1167. doi: 10.1097/CM9.0000000000001418.
Hepatitis B core-related antigen (HBcrAg) is a promising disease-monitoring marker for chronic hepatitis B (CHB). We investigated correlations between HBcrAg with antiviral efficacy and virological and histological variables.
One hundred and forty-five CHB patients from the mainland of China between August 2013 and September 2016 who underwent liver biopsy received entecavir therapy and had paired liver biopsy at 78 weeks. We analyzed correlations between HBcrAg and virological and histological variables in hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients. We also explored the predictors of HBeAg loss after 78 weeks of antiviral therapy. Pearson correlation analysis and logistic forward stepwise regression were the main statistic methods.
HBeAg-positive patients (n = 93) had higher baseline HBcrAg (median 7.4 vs. 5.3 log10 U/mL P < 0.001) and greater HBcrAg declines (median 1.6 vs. 0.9 log10 U/mL P = 0.007) than HBeAg-negative patients after 78 weeks of therapy. At baseline, HBcrAg correlated with hepatitis B virus (HBV) DNA in both HBeAg-positive (r = 0.641, P < 0.001) and -negative patients (r = 0.616, P < 0.001), with hepatitis B surface antigen (HBsAg) in HBeAg-positive patients (r = 0.495, P < 0.001), but not with anti-hepatitis B virus core antibody (anti-HBc). Weak correlations existed between HBcrAg, histology activity index (HAI; r = 0.232, P = 0.025), and Ishak fibrosis score (r = -0.292, P = 0.005) in HBeAg-positive patients. At 78 weeks, significant correlations existed only between HBcrAg and anti-HBc in HBeAg-positive (r = -0.263, P = 0.014) and HBeAg-negative patients (r = -0.291, P = 0.045). Decreased HBcrAg significantly correlated with reduced HBV DNA (r = 0.366, P = 0.001; r = 0.626, P < 0.001) and HBsAg (r = 0.526, P = 0.001; r = 0.289, P = 0.044) in HBeAg-positive and -negative patients, respectively, and with reduced HAI in HBeAg-positive patients (r = 0.329, P = 0.001). Patients with HBeAg loss (n = 29) showed a larger reduction in HBcrAg than those without (median 2.3 vs. 1.3 log10 U/mL, P = 0.001). In multivariate analysis, decreased HBcrAg was an independent predictor of HBeAg loss (P = 0.005).
HBcrAg reflects viral replication and protein production. Decreased HBcrAg could predict HBeAg loss after antiviral therapy.
Clinical Trials.gov: NCT01962155; https://www.clinicaltrials.gov/ct2/show/NCT01962155?term=NCT01962155&draw=2&rank=1.
乙型肝炎核心相关抗原（HBcrAg）是慢性乙型肝炎（CHB）疾病监测的有前途的标志物。我们研究了 HBcrAg 与抗病毒疗效以及病毒学和组织学变量之间的相关性。
2013 年 8 月至 2016 年 9 月，我们从中国大陆招募了 145 名接受恩替卡韦治疗并在 78 周时接受肝活检的 CHB 患者。我们分析了 HBeAg 阳性和 HBeAg 阴性患者中 HBcrAg 与病毒学和组织学变量之间的相关性。我们还探讨了抗病毒治疗 78 周后 HBeAg 丢失的预测因素。主要的统计方法是 Pearson 相关分析和逐步向前逻辑回归。
HBeAg 阳性患者（n=93）基线时的 HBcrAg 更高（中位数 7.4 比 5.3 log10 U/mL，P<0.001），治疗 78 周后 HBcrAg 下降幅度更大（中位数 1.6 比 0.9 log10 U/mL，P=0.007）。在基线时，HBcrAg 与 HBeAg 阳性（r=0.641，P<0.001）和阴性（r=0.616，P<0.001）患者的乙型肝炎病毒（HBV）DNA 相关，与 HBeAg 阳性患者的乙型肝炎表面抗原（HBsAg）相关（r=0.495，P<0.001），但与抗乙型肝炎病毒核心抗体（抗-HBc）无关。HBcrAg 与 HBeAg 阳性患者的组织学活动指数（HAI；r=0.232，P=0.025）和 Ishak 纤维化评分（r=-0.292，P=0.005）之间存在弱相关。在 78 周时，仅在 HBeAg 阳性（r=-0.263，P=0.014）和 HBeAg 阴性患者（r=-0.291，P=0.045）中，HBcrAg 与抗-HBc 之间存在显著相关性。HBcrAg 的降低与 HBV DNA（r=0.366，P=0.001；r=0.626，P<0.001）和 HBsAg（r=0.526，P=0.001；r=0.289，P=0.044）的降低显著相关，在 HBeAg 阳性患者中，与 HAI 的降低显著相关（r=0.329，P=0.001）。HBeAg 丢失的患者（n=29）的 HBcrAg 降低幅度大于未丢失的患者（中位数 2.3 比 1.3 log10 U/mL，P=0.001）。多变量分析显示，HBcrAg 的降低是 HBeAg 丢失的独立预测因素（P=0.005）。
HBcrAg 反映病毒复制和蛋白产生。HBcrAg 的降低可预测抗病毒治疗后的 HBeAg 丢失。
ClinicalTrials.gov：NCT01962155；https://www.clinicaltrials.gov/ct2/show/NCT01962155?term=NCT01962155&draw=2&rank=1。
