摘要
目的探讨乙型肝炎核心抗体(抗-HBc)预测乙型肝炎表面抗原(HBsAg)清除的可能性。方法60例既往经聚乙二醇干扰素α-2a联合核苷(酸)类似物(NAs)抗病毒治疗的慢性乙型肝炎患者,根据能否获得HBsAg清除,分为清除组41例,未清除组19例。通过双抗原夹心法检测基线和疗程中24、48、72周及96周患者的抗-HBc定量水平。采用Logistic回归分析和受试者操作特征曲线(ROC)评价相关影响因素对HBsAg清除的预测能力。结果随着抗病毒治疗的延长,总体人群、清除组和未清除的抗-HBc定量水平均呈进行性下降趋势,但清除组的抗-HBc水平在基线和抗病毒治疗过程中的连续检测时间点均显著高于未清除组(P值均<0.05)。多因素Logistic回归示:基线抗-HBc定量水平、24周HBsAg下降幅度(单位:log_(10) IU/ml)、治疗中丙氨酸转氨酶(ALT)>1.5倍正常值上限(ULN)均为HBsAg清除的影响因素(分别为OR=0.156,P=0.026;OR=0.134,P=0.023;OR=0.239,P=0.028)。其中,基线抗-HBc定量水平是预测HBsAg清除的最佳独立预测因子(OR=0.235;P=0.004),当其>3.40 log_(10) IU/ml时预测HBsAg清除的敏感性和特异性分别为56.1%和89.5%。为提高预测准确性,借鉴Logistic回归模型构建联合预测因子的方法,其中联合因子3的预测价值最高(ROC曲线下面积可达0.870;95%CI为0.781~0.960;P<0.001);联合因子3的cut-off值为>0.386,敏感性和特异性分别为80.5%和78.9%。运用联合指标可进一步提高预测价值,以基线抗-HBc定量水平为基础的任意两个指标或两个以上指标的联合,预测HBsAg清除率可达到94.12%~100%。结论基线抗-HBc定量水平的HBsA清除的预测价值最高,与治疗中ALT>1.5×ULN和24周HBsAg下降幅度联合能更精准的预测HBsAg清除,是可靠的非侵入性生物标志物。
Objective To explore the possibility of hepatitis B core antibody(anti-HBc)in predicting hepatitis B virus surface antigen(HBsAg)clearance.Methods Sixty cases with chronic hepatitis B who were previously treated with peginterferonα-2a combined with nucleos(t)ide analogues(NAs)antiviral therapy were divided according to the HBsAg clearance or non-clearance;41 cases in the clearance group and 19 cases in the non-clearance group.Double antigen sandwich method was used to detect patients anti-HBc quantitative levels during the course of treatment and at baseline,24,48,72 and 96 weeks.Logistic regression analysis and receiver operating characteristic curve(ROC)were used to evaluate the predictive ability of related influencing factors for HBsAg clearance.Results With antiviral treatment prolongation,anti-HBC quantitative levels in the overall population showed a progressive downward trend in the clearance group and the non-clearance group,but the anti-HBC level in the clearance group was significantly higher than non-clearance group at the baseline and successive detection time points during the antiviral treatment(P<0.05).Multivariate logistic regression showed that baseline quantitative anti-HBC level,HBsAg decline at week 24(log_(10) IU/ml),and alanine aminotransferase(ALT)>1.5 times the upper limit of normal value(ULN)were all influencing factors for HBsAg clearance during the treatment(OR=0.156,P=0.026;OR=0.134,P=0.023;OR=0.239,P=0.028).Among them,the baseline quantitative anti-HBc level was the best independent predictor for HBsAg clearance(OR=0.235;P=0.004),and the sensitivity and specificity for predicting HBsAg clearance at>3.40 log_(10) IU/mL were 56.1%and 89.5%,respectively.Logistic regression model was used as a reference to construct combined predictors in order to improve the prediction accuracy.Among them,the combined factor 3 had the highest predictive value(the area under the ROC curve had reached up to 0.870;95%CI was 0.781~0.960;P<0.001).The cut-off value of combined factor 3 was>0.386,and the sensitivity and specificity were 80.5%and 78.9%,respectively.In addition,the combined index had further improved the predictive value,which is the combination of any two or more indexes based on the baseline quantitative anti-HBC level,and HBsAg clearance predictive rate had reached 94.12%~100%.Conclusion The baseline quantitative anti-HBC level has the highest predictive value for HBsAg clearance.The combination of ALT>1.5×ULN and HBsAg decline at 24 weeks during the treatment can more precisely predict HBsAg clearance.Therefore,it is a reliable non-invasive biomarker.
作者
林潇
王晓晓
宋爱心
鲁俊峰
柳雅立
金怡
曹振环
马丽娜
郑燕红
陈新月
Lin Xiao;Wang Xiaoxiao;Song Aixin;Lu Junfeng;Liu Yali;Jin Yi;Cao Zhenhuan;Ma Lina;Zheng Yanhong;Chen Xinyue(Fist Department of Liver Disease Center,Beijing Youan Hospital,Capital Medical University,Beijing 100069,China)
出处
《中华肝脏病杂志》
CSCD
北大核心
2021年第7期673-678,共6页
Chinese Journal of Hepatology
基金
"十三五"国家科技重大专项课题(2017ZX10202201,2017ZX10201201-001-008,2017ZX10302201-004-003,2017ZX10202202-005-010)
首都卫生发展科研专项项目(首发2020-1-2181)
北京市属医院科研培育项目(pX2017057)。
