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[HBeAg阳性慢性乙型肝炎患者血清HBsAg水平、HBsAg/HBV DNA比值及其与肝脏炎症活动度的相关性的临床意义]

[Clinical significance of serum HBsAg levels, HBsAg/HBV DNA ratio, and association with liver inflammation activity in HBeAg-positive chronic hepatitis B].

作者信息

Li Ge, Wang Jie, Bao Yanting, Zheng Liangda, Ge Ke, Zhou Xiang, Chen Gongying

机构信息

The sixth Hospital Affiliated to Zhejiang Chinese Medicine University, Hangzhou 310015, China.

出版信息

Zhonghua Gan Zang Bing Za Zhi. 2015 Jan;23(1):40-5. doi: 10.3760/cma.j.issn.1007-3418.2015.01.010.

DOI:10.3760/cma.j.issn.1007-3418.2015.01.010
PMID:25751385
Abstract

OBJECTIVE

To study the clinical significance of hepatitis B surface antigen (HBsAg) levels and HBsAg/hepatitis B virus (HBV) DNA ratio in relation to liver inflammation in HBeAg-positive chronic hepatitis B (CHB).

METHODS

One hundred and fifty-three Chinese patients with chronic HBV infection with HBeAg-positive status were enrolled in the study.Quantitative measurements were made for HBsAg levels by immunoassay (Architect HBsAg QT by Abbott Diagnostic) and HBV DNA by real-time fluorescence quantitative PCR.Levels of liver function markers were measured by standard methods.Liver biopsy specimens were obtained from all patients and used to score the histology (liver inflammation) activity index (HAI) and grade (G) the extent of necroinflammation.Statistical correlation analysis was performed to determine the association of HBsAg titre or HBsAg/HBV DNA ratio with the various parameters of liver injury.

RESULTS

HBsAg titre and HBsAg/HBV DNA ratio were significantly correlated (r =0.578, P less than 0.0001).A significant positive correlation (r =0.642, P less than 0.0001) was found between HBsAg titre and HBV DNA load, and a significant negative correlation was found between the HAI and HBsAg (r =-0.389, P less than 0.0001) and HBsAg/HBV DNA ratio (r =-0.307, P=0.000l).A significant positive correlation was found between alanine aminotransferase (ALT) level and the HAI (r =0.480, P less than 0.0001).Patients with G less than 2 necroinflammation had significantly higher HBsAg titre and HBsAg/HBV DNA ratio than patients with G more than or equal to 2 necroinflammation (both P less than 0.01) but similar levels ofHBV DNA.Generation of a receiver operating characteristic curve using G more than or equal to 2 as the positive index provided the following area under the curve (AUC) values:HBsAg titre, 0.700; HBsAg/HBV DNA ratio, 0.672; ALT level, 0.713.When the random chance AUC was 0.5, all levels of AUC were statistically significant (Pless than 0.001).HBsAg titre (sensitivity =76.92%) was more sensitive than ALT level (sensitivity =76.92%), and HBsAg/HBV DNA ratio (specificity =81.33%) was more specific than ALT level (specificity =81.33%).Youden's index for comprehensive evaluation using ALT was higher than those for HBsAg titre or HBsAg/HBV DNA ratio.When HBsAg and ALT were considered in parallel, the sensitivity increased to 94.08% and specificity rose to 85.60%.

CONCLUSION

HBsAg titre, HBsAg/HBV DNA ratio and ALT levels can be used as the index for judging the degree of liver inflammation in HBeAg-positive CHB patients.Higher sensitivity and specificity are attained when HBsAg and ALT are used in series or parallel.

摘要

目的

研究乙肝表面抗原(HBsAg)水平及HBsAg/乙肝病毒(HBV)DNA比值与HBeAg阳性慢性乙型肝炎(CHB)肝脏炎症的临床意义。

方法

153例HBeAg阳性的慢性HBV感染中国患者纳入本研究。采用免疫分析法(雅培诊断公司的Architect HBsAg QT)定量检测HBsAg水平,采用实时荧光定量PCR检测HBV DNA。采用标准方法检测肝功能指标水平。所有患者均获取肝活检标本,用于组织学(肝脏炎症)活动指数(HAI)评分及坏死性炎症程度分级(G)。进行统计相关性分析以确定HBsAg滴度或HBsAg/HBV DNA比值与肝损伤各项参数之间的关联。

结果

HBsAg滴度与HBsAg/HBV DNA比值显著相关(r = 0.578,P < 0.0001)。HBsAg滴度与HBV DNA载量之间存在显著正相关(r = 0.642,P < 0.0001),HAI与HBsAg(r = -0.389,P < 0.0001)及HBsAg/HBV DNA比值(r = -0.307,P = 0.0001)之间存在显著负相关。丙氨酸氨基转移酶(ALT)水平与HAI之间存在显著正相关(r = 0.480,P < 0.0001)。坏死性炎症G<2的患者HBsAg滴度及HBsAg/HBV DNA比值显著高于G≥2的患者(均P < 0.01),但HBV DNA水平相似。以G≥2作为阳性指标生成受试者操作特征曲线,得到以下曲线下面积(AUC)值:HBsAg滴度为0.700;HBsAg/HBV DNA比值为0.672;ALT水平为0.713。当随机概率AUC为0.5时,所有AUC水平均具有统计学意义(P < 0.001)。HBsAg滴度(灵敏度 = 76.92%)比ALT水平(灵敏度 = 76.92%)更敏感,HBsAg/HBV DNA比值(特异度 = 81.33%)比ALT水平(特异度 = 81.33%)更特异。使用ALT进行综合评估的约登指数高于HBsAg滴度或HBsAg/HBV DNA比值。当同时考虑HBsAg和ALT时,灵敏度增至94.08%,特异度升至85.60%。

结论

HBsAg滴度、HBsAg/HBV DNA比值及ALT水平可作为判断HBeAg阳性CHB患者肝脏炎症程度的指标。HBsAg与ALT串联或并联使用时可获得更高的灵敏度和特异度。

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