摘要
目的监测HBsAg浓度在恩替卡韦（ETV）治疗的HBeAg阳性的慢性乙型肝炎（CHB）患者血清中的动态变化，探讨其对治疗反应的预测价值。方法回顾性研究。选择2011年1月至2013年7月在福建医科大学附属第一医院肝病中心住院及门诊接受ETV治疗（0．5mg／d）的HBeAg阳性CHB患者26例，并进行1年的随访研究；于抗病毒治疗的0、3、6、9、12个月分别收集血清；化学发光法定量检测各时间点的HBsAg、HBeAg浓度；实时荧光PCR定量检测血清HBVDNA载量；速率法检测ALT含量；1年病毒学应答定义为抗病毒治疗1年后血清HBVDNA低于检测下限（500IU／m1）；统计学分析采用正态性检验、t检验、，检验、相关性程度分析、绘制ROC曲线。结果17例患者发生病毒学应答（VR＋），9例未发生病毒学应答（VR-）；基线ALT水平VR＋组[（141．82±77．29）IU／ml]与VR-组[（134．20±49．76）IU／mlJ无明显差别（t=0．27，P=0．793）；HBVDNAVR＋组[（6．76±1．00）lgIU／m1]明显低于VR-组[（7．65±0．87）lg1U／ml]（t=-2．27，P=0．033）；HBsAg浓度VR＋组[（3．79±0．61）lgIU／ml]与VR-组[（4．19±0．43）lgIU／ml]无明显差别（t=-1．75，P=0．094）；HBsAg与HBVDNA水平呈正相关（r=0．45，P=0．02）。HBsAg在治疗开始的前3个月下降较快，3个月后下降较缓慢。从基线到治疗3个月时，VR＋组HBsAg平均下降（0．324-0．29）lgIU／ml，VR一组下降（0．14±0．10）lgIU／ml，差异具有统计学意义（t=2．245，P=0．035）；治疗3个月时lgHBsAg浓度的ROC曲线下面积最大（AUC=0．840，P=0．022），临界值3．8650lgIU／ml的Youden指数最大（0．602），其诊断敏感度为82．4％，特异度为77．8％。结论ETV治疗3个月时lgHBsAg≤3．86501U／ml可作为预测ETV治疗1年病毒学应答的指标。（中华捡验医学杂志，2014，37：96—99）
Objective To monitor the dynamic changes of quantitative hepatitis B surface antigen concentrations in HBeAg-positive treatment-naive CHB patients and to investigate its potential role in predicting virological response to entecavir therapy. Methods This was a retrospective study. 26 HBeAg- positive treatment-naive CHB patients receiving ETV （0.5 mg once a day） were consecutively recruited and followed up for 1 year from the Center of Liver diseases of the First Affiliated Hospital of Fujian Medical University between January 2011 and July 2013. Serums samples were collected at baseline and every 3 months （month 3, month 6, month 9 and month 12, respectively）. HBsAg and HBeAg concentrations were measured using commercially available chemiluminescence assay. HBV DNA levels were determined by real- time polymerase chain reaction. ALT levels were measured by velocity method. A VR（virological response） was defined as HBV DNA levels decreased to less than 500 IU/ml through 1 year of ETV treatment. The statistical analyses including Student t-test, X2-test, ROC curve analysis, etc. were performed using statistical analysis software SPSS version 16.0 and GraphPad Prism software version 5.0. Results After 1 year of treatment, 17 patients achieved VR, 9 patients didnt. Baseline characteristics of the patients were as follows ： there was no significant difference of ALT levels between the VR ＋ group and VR - group （ 141.82 ± 77.29 IU/ml and 134.2±49.76 IU/ml, respectively, t =0.27, P =0.793）. HBV DNA levels of VR ＋ group was signi？ cantly lower than that of the VR - group （6.76 ± 1.00 lg IU/ml and 7.65 ±0.87 lg IU/ ml, respectively, t = - 2.27, P = 0. 033）. HBsAg concentration of the VR ＋ group was lower than that of the VR - group, but showed no-statistically significant （3.79 ±0.61 lg IU/ml and 4.19 ±0.43 lg IU/ml, respectively, t = - 1.75 P = 0. 094）. A rapid decline in HBsAg concentration during the first 3 months of therapy followed by a much slower decline in the subsequent period was observed. From baseline to month 3, the reductions of HBsAg concentration were 0. 32 ± 0.29 and 0. 14 ±0. 10 lg IU/ml in VR ＋ and VR - groups （t = 2. 245, P = 0. 035 ） , respectively. The lg HBsAg concentration at month 3 showed the biggest area under the curve （AUC） （AUC = 0. 840, P = 0. 005）. The best cut-off value for the HBsAg concentration at month 3 for the prediction of VR was 3. 8650 lg IU/ml, with a diagnostic sensitivity and specificity of 82.4% and 77.8%, respectively. Conclusions HBsAg level less than or equal to 3. 8650 lg IU/ml at month 3 of ETV treatment may be a useful parameter in predicting virological response to ETV in HBeAg-positive CHB patients.
出处
《中华检验医学杂志》
CAS
CSCD
北大核心
2014年第2期96-99,共4页
Chinese Journal of Laboratory Medicine
基金
国家自然科学基金资助项目（81371888）
福建省高校产学合作科技重大项目（2013Y4002）
福建省科技计划重点项目（2011Y0023）
