|
摘要：
|
|
摘要：目的 探讨乙型肝炎病毒e抗原（hepatitis B virus e antigen，HBeAg）阳性慢性
乙型肝炎（chronic hepatitis B，CHB）患者恩替卡韦（entecavir，ETV）治疗中乙型
肝炎病毒核心相关抗原（hepatitis B virus core-related antigen，HBcrAg）水平变化及
其对治疗效果的预测价值。方法 选取2019年1月至2019年9月保定市人民医院收治的133例
HBeAg阳性CHB患者为研究对象。所有患者均给予ETV治疗至少48周。以治疗48周内
是否完全应答分为完全应答（59例）和非完全应答（74例）。采用荧光定量PCR检测
HBV DNA水平，采用全自动免疫分析仪检测HBeAg和HBsAg水平，采用化学发光酶
免疫法检测HBcrAg水平，采用全自动生化分析仪检测丙氨酸氨基转移酶（alanine
aminotransferase，ALT）、天门冬氨酸氨基转移酶（aspartate aminotransferase，
AST）、白蛋白（albumin，ALB）及肌酐（creatinine，Cr）水平。HBcrAg与HBV
DNA、HBeAg、HBsAg的相关性采用Pearson相关性分析。采用受试者工作特征
（receiver operator characteristic，ROC）曲线分析HBcrAg对HBeAg阳性CHB患者完全
应答的预测价值。结果 完全应答组患者基线HBV DNA [（5.22 ± 1.25）lg IU/ml vs（6.57 ±
1.50）lg IU/ml]、HBeAg [（2.53 ± 0.56）lg S/CO vs（3.82 ± 0.46）lg S/CO]、HBsAg
[（3.34 ± 0.77）lg IU/ml vs（3.91 ± 0.83）lg IU/ml]、HBcrAg [（7.69 ± 2.33）lg U/ml vs
（8.36 ± 2.67）lg U/ml] 水平显著低于非完全应答组患者（P均＜ 0.05）。Logistic多因
素回归分析表明，HBV DNA（OR = 27.139，95%CI：8.760～84.077，P ＜ 0.001）、
HBeAg（OR = 2.382，95%CI：1.505～3.768，P ＜ 0.001）、HBsAg（OR = 1.197，
95%CI：1.043～1.374，P = 0.011）、HBcrAg（OR = 1.962，95%CI：1.478～2.605，P ＜
0.001）均为HBeAg阳性CHB患者48周内非完全应答的危险因素（P ＜ 0.05）。完全应
答组患者基线、治疗12周、治疗24周、治疗48周HBcrAg水平分别为（7.20 ± 2.33）lg U/ml、
（6.12 ± 2.10）lg U/ml、（5.73 ± 2.01）lg U/ml、（5.51 ± 1.52）lg U/ml，非完全应答
组分别为（8.36 ± 2.67）lg U/ml、（7.83 ± 2.43）lg U/ml、（7.16 ± 1.87）lg U/ml、（6.43 ±
1.73）lg U/ml。重复测量方差分析表明，两组间差异有统计学意义（F组别 = 23853，
P组别 ＜ 0.001），各时间点差异有统计学意义（F时间 = 73.134，P时间 ＜ 0.001），组别
和时间无交互作用（F交互 = 0.514，P交互 = 0.084）。完全应答组基线、治疗12周、治疗
24周及治疗48周HBcrAg水平均显著低于非完全应答组（P均＜ 0.05）。完全应答组治
疗12周、治疗24周及治疗48周HBcrAg水平均显著低于基线（P ＜ 0.05）；非完全应答
组治疗24周、治疗48周HBcrAg水平显著低于基线（P ＜ 0.05）。Pearson相关性分析表
明，HBcrAg与HBV DNA、HBeAg和HBsAg均呈显著正相关（r值分别为0.804、0.875、
0.863，P均＜ 0.001）。基线HBcrAg预测HBeAg阳性CHB患者完全应答的ROC曲线下
面积为0.783（渐进95%CI：0.704～0.861），HBcrAg为7.695 lg U/ml时预测价值最高，
敏感度为0.730、特异度为0.729。结论 HBV DNA、HBeAg、HBsAg、HBcrAg等HBV相
关标志物均为ETV治疗48周后HBeAg阳性CHB患者非完全应答的危险因素，且在治疗
过程中伴随着HBcrAg的变化，HBcrAg对于患者非完全免疫应答具有预测价值。
|
|
Abstract: Objective To investigate the levels and predictive value of hepatitis B virus corerelated antigen (HBcrAg) in chronic hepatitis B (CHB) patients with hepatitis B virus e antigen
(HBeAg) positive in treatment with entecavir (ETV). Methods A total of 133 CHB patients
with HBeAg positive in Baoding People’s Hospital from January 2019 to September 2019
were selected. All patients were treated with ETV for at least 48 weeks. The patients were
divided into complete response group (59 cases) and incomplete response group (74 cases)
according to the response status within 48 weeks. The level of HBV DNA was detected
by fluorescence PCR, HBeAg and HBsAg were detected by automatic immune analyzer,
HBcrAg was detected by chemiluminescent enzyme immunoassay, alanine aminotransferase
(ALT), aspartate aminotransferase (AST), albumin (ALB) and creatinine (Cr) were detected
by automatic biochemical analyzer. The correlation of HBcrAg and HBV DNA, HBeAg
and HBsAg were analyzed by Pearson correlation analysis. The predictive value of HBcrAg
for the complete response of CHB patients with HBeAg positive was analyzed by receiver
operator characteristic (ROC) curve. Results The baseline HBV DNA [(5.22 ± 1.25) lg IU/ml
vs (6.57 ± 1.50) lg IU/ml], HBeAg [(2.53 ± 0.56) lg S/CO vs (3.82 ± 0.46) lg S/CO], HBsAg
[(3.34 ± 0.77) lg IU/ml vs (3.91 ± 0.83) lg IU/ml] and HBcrAg [(7.69 ± 2.33) lg U/ml
vs (8.36 ± 2.67) lg U/ml] levels of patients in complete response group were significantly
lower than those in incomplete response group (all P ＜ 0.05). Logistic multivariate
regression analysis showed that HBV DNA (OR = 27.139, 95%CI: 8.760～84.077, P ＜ 0.001),
HBeAg (OR = 2.382, 95%CI: 1.505～3.768, P ＜ 0.001), HBsAg (OR = 1.197, 95%CI:
1.043～1.374, P = 0.011) and HBcrAg (OR = 1.962, 95%CI: 1.478～2.605, P ＜ 0.001) were
risk factors for incomplete response with 48 weeks of CHB patients with HBeAg positive.
HBcrAg level of patients in complete response group at baseline, 12 weeks, 24 weeks and
48 weeks of treatment were (7.20 ± 2.33) lg U/ml, (6.12 ± 2.10) lg U/ml, (5.73 ± 2.01) lg U/ml and
(5.51 ± 1.52) lg U/ml,respectively, which were (8.36 ± 2.67) lg U/ml, (7.83 ± 2.43) lg U/ml,
(7.16 ± 1.87) lg U/ml and (6.43 ± 1.73) lg U/ml, respectively in incomplete response group.
Variance analysis of repeated measurement showed that there were significant differences
between the two groups (Fgroup = 23853, Pgroup ＜ 0.001) and at each time point (Ftime = 73.134,
Ptime ＜ 0.001), and there was no interaction between time and groups (Finteractive = 0.514,
Pinteractive = 0.084). HBcrAg levels of patients in complete response group at baseline,
12 weeks, 24 weeks and 48 weeks of treatment were significantly lower than those in
incomplete response group (all P ＜ 0.05). HBcrAg levels of patients in complete response
group at 12 weeks, 24 weeks and 48 weeks of treatment were significantly lower that than at
baseline (all P ＜ 0.05). HBcrAg levels of patients in incomplete response group at 24 weeks
and 48 weeks of treatment were significantly lower than that at baseline (all P ＜ 0.05). Pearson
correlation analysis showed that HBcrAg had significantly positive associations with HBV
DNA, HBeAg and HBsAg (r = 0.804, 0.875, 0.863; all P ＜ 0.001). The area under the ROC
curve of baseline HBcrAg predicted complete response in CHB patients with HBeAg positive
was 0.783 (progressive 95%CI: 0.704～0.861), with the highest predictive value at HBcrAg of
7.695 lg U/ml, the sensitivity was 0.730 and the specificity was 0.729. Conclusions HBVrelated markers such as HBV DNA, HBeAg, HBsAg and HBcrAg were all risk factors for
incomplete response in CHB patients with HBeAg positive after 48 weeks of ETV treatment,
and were accompanied by changes in HBcrAg during treatment. HBcrAg had a predictive
value for patients with noncomplete immune responses.
|
|
基金项目：
|
|
|
|
作者简介：
|
|
|
|
参考文献：
|
|
|
|
服务与反馈：
|
|
【文章下载】【加入收藏】
|
|
|
|