抗-HBc半定量水平联合早期病毒学应答预测干扰素治疗慢性乙型肝炎的疗效

摘要/Abstract

摘要： 目的探讨血清抗-HBc半定量水平联合早期病毒学应答在预测干扰素初治的HBeAg阳性慢性乙型肝炎患者48周HBeAg血清学转换中的价值。方法回顾性分析2013年1月至2019年1月在上海市公共卫生临床中心就诊的干扰素初治的HBeAg阳性慢性乙型肝炎患者96例,所有患者均采用聚乙二醇干扰素治疗48周。治疗前及治疗期间每隔12周采用化学发光微粒子免疫分析法检测核心抗体水平。组间比较采用Mann -Whitney U检验和Kruskal-Wallis H检验,应用受试者工作特征(ROC)曲线评估预测效能。结果实现血清学应答的患者基线抗-HBc水平为11.92(10.07~12.80) s/co,未发生血清学应答患者为10.61(9.49~11.47)s/co。单因素logistic回归分析发现,基线抗-HBc水平(OR=1.469,95%CI:1.137~1.898, P<0.01)和早期病毒学应答(OR=3.507,95%CI:1.051~11.69, P=0.041)与干扰素治疗血清学应答具有独立相关性,多因素二元logistic回归分析提示,基线抗-HBc水平(OR=1.831,95%CI:1.299~2.582, P<0.01)及早期病毒学应答(OR=2.161,95%CI:1.595~7.851, P=0.024)对干扰素治疗的血清学应答有一定的预测价值。当基线抗-HBc水平cut off值为11.6 s/co时,ROC曲线下面积最大(AUROC=0.72,95%CI:0.59~0.86,P=0.004),诊断敏感度和特异度分别为73.42%和64.71%。将基线抗-HBc水平根据预测48周发生HBeAg血清学转换的cut-off值11.6 s/co和是否发生早期病毒学应答进行分层,基线抗-HBc≥11.6 s/co且实现早期病毒学应答时,48周HBeAg血清学转换率最高为42.86%(9/21);仅满足基线抗-HBc≥11.6 s/co或仅满足早期病毒学应答时,HBeAg血清学转换率分别为18.18%(2/11)和12.12%(4/33);当基线抗-HBc<11.6 s/co且未实现早期病毒学应答时,HBeAg血清学转换率为0.06%(2/31)。结论基线核心抗体的半定量水平联合早期病毒学应答,可以作为HBeAg阳性慢性乙型肝炎初治患者干扰素治疗效果的预测因子。

关键词: 慢性乙型肝炎, 干扰素, 核心抗体, 早期病毒学应答

Abstract: Objective To investigate the value of semi-quantitative detection of hepatitis B core antibody (HBcAb) combined with early virological response in predicting hepatitis B envelope antigen (HBeAg) seroconversion in HBeAg-positive chronic hepatitis B (CHB) patients treated with peginterferon initially.Methods A total of 96 HBeAg-positive CHB patients in our hospital from January 2013 to January 2019 were retrospectively analyzed. All patients were initially treated with peginterferon for 48 weeks. The level of HBcAb was measured by chemiluminescent microparticle immunoassay before and during treatment every 12 weeks. Mann-Whitney U test and Kruskal-Wallis H test were used to determine intergroup differences. Receiver operating characteristic (ROC) curve was used to calculate the diagnostic value.Results Baseline HBcAb levels of patients who achieved serological response were higher (11.92, 10.07-12.80 vs 10.61, 9.49-11.47, P=0.003). Univariate logistic regression analysis showed that baseline HBcAb level (odds ratio [OR]=1.469, 95% confidence interval: 1.137-1.898, P=0.003) and achievement of early virological response (OR=3.507, 95% CI: 1.051-11.69, P=0.041) were independently related to serological response of peginterferon. Multivariate binary logistic regression analysis suggested that baseline HBcAb level (OR=1.831, 95% CI: 1.299-2.582, P=0.001) and early virological response (OR=2.161, 95% CI: 1.595-7.851, P=0.024) could predict serological response in CHB patients receiving peginterferon. The cut-off value of baseline HBcAb was 11.6 S/CO with the area under the ROC curve of 0.72 (95% CI: 0.59-0.86, P=0.004), and the diagnostic sensitivity and specificity were 73.42% and 64.71%, respectively. Patients were stratified according to the baseline HBcAb cut-off value of 11.6 S/CO and the achievement of early virological response. The HBeAg seroconversion rate at week 48 of patients who achieved early virological response with baseline HBcAb ≥ 11.6 S/CO was 42.86%. The HBeAg seroconversion rates at week 48 of patients with either baseline HBcAb ≥ 11.6 S/CO or early virological response were 18.18% (2/11) and 12.12% (4/33). And only 0.06% (2/31) achieved HBeAg seroconversion among patients with baseline HBcAb < 11.6 S/CO and without early virological response.Conclusion The semi-quantitative detection of baseline HBcAb combined with early virological response may serve as a simple and valuable predictor of serological response in HBeAg-positive CHB patients receiving peginterferon initially, guiding physicians in clinical practice.

Key words: Chronic hepatitis B, Peginterferon, Hepatitis B core antibody, Early virological response

王倩倩, 胡乾坤, 张毅, 方钟, 黄晨璐, 许伟, 陈良, 黄玉仙. 抗-HBc半定量水平联合早期病毒学应答预测干扰素治疗慢性乙型肝炎的疗效[J]. 肝脏, 2019, 24(9): 1002-1006.

WANG Qian-qian, HU Qian-kun, ZHANG Yi, FANG Zhong, HUANG Chen-lu, XU Wei, CHEN Liang, HUANG Yu-xian. Combination of hepatitis B core antibody and early virological response for predicting serological response in hepatitis B patients receiving peginterferon[J]. Chinese Hepatolgy, 2019, 24(9): 1002-1006.

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