血清定量HBsAg和HBV DNA预测HBeAg阳性慢性HBV感染显著肝炎活动的性能比较

Performance comparison of quantitative serum HBsAg and HBV DNA in predicting significant hepatitis activity in patients with HBeAg-positive chronic HBV infection

目的 对比评价血清HBsAg和HBV DNA预测HBeAg阳性慢性HBV感染显著肝炎活动的性能。方法 505例HBeAg阳性患者入选本研究。HBsAg、HBeAg采用Architect I2000免疫分析仪检测,HBV DNA采用LightCycler 480 qPCR仪检测;血清ALT采用Architect C16000生化分析仪检测。肝脏病理学分级和分期参照Scheuer标准。显著肝炎活动分三个层级,依次定义为“ALT≥20 IU/L或(分级>G1或分期>S1)”、“ALT≥30 IU/L或(分级>G1或分期>S1)”、“ALT≥40 IU/L或(分级>G1或分期>S1)”。结果 根据ALT与HBsAg、HBeAg和HBV DNA的LOESS回归分析,279例患者被界定为疑似HBV高复制人群。总体人群,HBsAg和HBV DNA预测三个层级显著肝炎活动的ROC曲线下面积(AUC)依次为0.737和0.532、0.737和0.548、0.686和0.545,疑似HBV高复制人群,HBsAg和HBV DNA预测三个层级显著肝炎活动的AUC依次为0.866和0.544、0.837和0.540、0.787和0.564。无论总体或疑似HBV高复制人群,HBsAg和HBV DNA预测三个层级显著肝炎活动的AUC分别均显著大于和均接近对角参考线下面积(P均<0.002和P均>0.150),HBsAg预测三个层级显著肝炎活动的AUC均显著大于HBV DNA(P<0.001)。以HBsAg≤4.699 log10 IU/mL为标准,其预测总体人群ALT≥20 IU/L、≥40 IU/L显著肝炎活动的灵敏度和特异度分别为86.50%和56.25%、89.52%和43.94%,预测疑似HBV高复制人群ALT≥20 IU/L、≥40 IU/L显著肝炎活动的灵敏度和特异度分别为75.37%和81.82%、80.51%和67.44%。结论 HBsAg对HBeAg阳性显著肝炎活动有良好预测意义,而HBV DNA没有预测价值。

Objective To comparatively evaluate the performance of serum HBsAg and HBV DNA in predicting significant hepatitis activity in HBeAg-positive patients with chronic HBV infection. Methods 505 HBeAg-positive patients were enrolled. HBsAg and HBeAg were measured in an Abbott Architect I2000 automatic immunoassay system, HBV DNA was measured in a Roche LightCycler 480 qPCR system, and serum ALT was measured in an Abbott Architect C16000 automatic biochemical analysis system. Diagnoses of Liver pathological grade and stage referred to the Scheuer standard. Significant hepatitis activity was divided into three levels, which were successively defined as “ALT≥20 IU/L or(pathological grade>G1 or stage>S1)”, “ALT≥30 IU/L or(pathological grade>G1 or stage>S1)”, and “ALT≥40 IU/L or(pathological grade>G1 or stage>S1)”. Results According to LOESS regression analyses of ALT with HBsAg, HBeAg and HBV DNA, 279 patients were classified as possible high HBV replication population. In the total number of infected, the areas under ROC curve(AUCs) of HBsAg and HBV DNA for predicting the three levels of significant hepatitis activity were successively 0.737 and 0.532, 0.737 and 0.548, and 0.686 and 0.545;in possible high HBV replication population, the AUCs of HBsAg and HBV DNA for predicting the three levels of significant hepatitis activity were successively 0.866 and 0.544, 0.837 and 0.540, and 0.787 and 0.564. In both overall and possible high HBV replication population, the AUCs of HBsAg and HBV DNA for predicting the three levels of significant hepatitis activity were all significantly greater than and all close to the area under diagonal reference line(all P<0.002 and all P>0.150);and the AUCs of HBsAg for predicting the three levels of significant hepatitis activity were all significantly greater than those of HBV DNA(P<0.001). With standard of HBsAg≤4.699 log10 IU/mL, the sensitivity and specificity of HBsAg for predicting significant hepatitis activity with ALT≥20 IU/L, ALT≥40 IU/L of overall population were 86.50% and 56.25%, 89.52% and 43.94%, respectively;and of possible high HBV replication population were 75.37% and 81.82%, 80.51% and 67.44%, respectively. Conclusion HBsAg has good performance and HBV DNA has no value in predicting significant hepatitis activity in patients with HBeAg-positive chronic HBV infection.