血清HBsAg、HBcrAg和HBV DNA预测慢性乙型肝炎肝组织病理状态的性能评价

Evaluation on predictive value of serum HBsAg,HBcrAg and HBV DNA for liver pathology in chronic hepatitis B patients

目的评价血清HBsAg、HBcrAg、HBV DNA预测慢性乙型肝炎肝组织病理状态的性能。方法将324例HBeAg阳性和255例HBeAg阴性慢性乙型肝炎患者随机分为3组匹配的训练集和验证集。血清HBsAg和HBcrAg分别采用Abbott Architect I2000和Fujirebio Lumipulse G1200全自动化学发光免疫系统检测,血清HBV DNA采用Bio-Rad Icycler荧光定量PCR仪检测。肝组织病理学诊断采用Scheuer评分系统,其中病理学分级包括G0~G4五级,分期包括S0~S4五期。结果无论HBeAg阳性或阴性患者,3个训练集与3个匹配的验证集性别比例和平均年龄、病理学分级和分期构成比之间的差异均无统计学意义（P〉0.05）。HBeAg阳性患者,血清HBsAg、HBcrAg、HBV DNA预测全集病理学分级≥G3和分期≥S4的ROC曲线下面积最大;参照预测3个训练集病理学分级≥G3和分期≥S4的最佳截断值,血清HBsAg、HBcrAg、HBV DNA预测3个匹配的验证集病理学分级≥G3和分期≥S4的灵敏度极差分别为37%和9%、30%和16%、17%和14%,特异度极差分别为12%和5%、13%和3%、15%和6%。HBeAg阴性患者,血清HBcrAg、HBV DNA预测全集病理学分级≥G2和分期≥S2的ROC曲线下面积最大;参照预测3个训练集病理学分级≥G2和分期≥S2的最佳截断值,血清HBcrAg、HBV DNA预测3个匹配的验证集病理学分级≥G2和分期≥S2的灵敏度极差分别为11%和20%、46%和19%,特异度极差分别为15%和2%、38%和16%。结论 HBeAg阳性患者,血清HBsAg、HBcrAg、HBV DNA可预测的最佳病理状态为病理学分级≥G3和分期≥S4,其预测理学分期≥S4的稳定性高于预测病理学分级≥G3;HBeAg阴性患者,血清HBcrAg和HBV DNA可预测的最佳病理状态为病理学分级≥G2和分期≥S2,血清HBcrAg预测病理学分级≥G2和分期≥S2的稳定性高于HBV DNA。

Objective To evaluate the predictive value of serum hepatitis B surface antigen（HBsAg）,hepatitis B core-related antigen（HBcrAg）and hepatitis B virus（HBV）DNA for liver pathology in chronic hepatitis B（CHB）patients.Methods CHB patients,containing 324 HBeAg-positive and 255 HBeAg-negative cases,were randomly divided into 3paired train and validation sets.Serum HBsAg and HBcrAg were measured by Lumipulse G1200 and Abbott Architect I2000 automatic chemiluminescence immunoassay analyzers,respectively.Serum HBV DNA was detected by Bio-Rad Icycler fluorescence quantitative PCR system.Scheuer scoring system was applied for pathological evaluation of liver tissues,containing 5 grades from G0 to G4 and 5 stages from S0 to S4.Results Gender ratio,average age and proportion of pathological grades and stages in 3 paired train and validation sets showed no statistically significant differences（P〈0.05）in both HBeAg positive and negative cases.In HBeAg-positive patients,the areas under receiver operating characteristic curve（ROC）of serum HBsAg,HBcrAg and HBV DNA for predicting≥ G3 and≥ S4 in complete set were the largest.Referring to the optimal cutoffs for predicting ≥ G3 and ≥ S4 in 3 train sets,the ranges of sensitivities of serum HBsAg,HBcrAg and HBV DNA for predicting ≥ G3 and ≥ S4 in the 3 matched validation sets were 37%,30%,17% and 9%,16%,14%,respectively.Meanwhile,the ranges of specificity were 12%,13%,15% and 5%,3%,6%,respectively.In HBeAg-negative patients,the areas under ROC of serum HBcrAg and HBV DNA for predicting≥ G2 and≥ S2 in complete set were the largest.Based on the optimal cutoffs in 3 train sets,the ranges of sensitivity of serum HBcrAg and HBV DNA for predicting≥ G2 and≥ S2 in the 3 matched validation sets were 11%,46% and 19%,20%,respectively,and the ranges of specificities were 15%,38% and 2%,16%,respectively.Conclusion In HBeAg-positive patients,serum HBsAg,HBcrAg and HBV DNA were suitable for predicting pathologic states of≥ G3 and≥ S4,and the stabilities for predicting ≥ S4 were better than those for predicting ≥ G3.In HBeAg-negative patients with pathologic states of≥ G2 and≥ S2,serum HBcrAg and HBV DNA were the best predictable indicators,and serum HBcrAg showed better stabilities than serum HBV DNA.