实用肝脏病杂志 ›› 2016, Vol. 19 ›› Issue (1): 20-24.doi: 10.3969/j.issn.1672-5069.2016.01.006

• 乙型肝炎 • 上一篇    下一篇

血清HBsAg和HBV DNA定量水平预测慢性乙型肝炎患者肝组织炎症活动度和纤维化程度的评价*

陆伟, 张占卿, 沈芳, 王雁冰, 丁荣蓉, 周新兰, 冯艳玲   

  1. 201508 上海市公共卫生临床中心肝炎二科(陆伟,张占卿,王雁冰,丁蓉荣,周新兰),检验科(沈芳), 病理科(冯艳玲)
  • 收稿日期:2015-03-31 出版日期:2016-01-10 发布日期:2016-02-04
  • 作者简介:陆伟,女,44岁,大学本科,主治医师。主要从事慢性乙型肝炎的基础与临床研究。E-mail:b33lw@163.com
  • 基金资助:
    *基金项目:上海市卫生和计划生育委员会重点科研项目(编号:20134032)

Serum HBsAg levels and HBV DNA loads in prediction of hepatic histological activity grading and fibrosis staging in patients with chronic hepatitis B

Lu Wei, Zhang Zhanqing, Shen Fang, Wang Yanbing, Ding Rongrong, Zhou Xinlan, Feng Yanling   

  1. Second Division,Department of Hepatology,Public Clinical Health Center,Fudan University,Shanghai 201508,China
  • Received:2015-03-31 Online:2016-01-10 Published:2016-02-04

摘要: 目的评价血清HBsAg水平和HBV DNA载量预测CHB患者肝组织炎症活动度和纤维化程度的效能。方法740例CHB患者被随机分成训练集和验证集,训练集HBeAg阳性和阴性患者分别为281例和169例,验证集HBeAg阳性和阴性患者分别为170例和120例。肝活检取得肝组织,将肝组织病理学分级和分期≥G2和≥S2、≥G3和≥S3、≥G4和≥S4分别定义为显著炎症和纤维化、严重炎症和纤维化、进展期炎症和纤维化。采用Abbott Architect I2000检测血清HBsAg,采用实时定量PCR法检测血清HBV DNA。结果在HBeAg阳性患者,训练集血清HBsAg水平预测严重纤维化和进展期纤维化的效能达到了中度,其ROC曲线下面积分别为0.707和0.726;基于Youden指数确定的血清HBsAg预测严重纤维化和进展期纤维化的最佳截断点为≤6.683×103 IU/ml和≤6.427×103 IU/ml,在训练集其对应的灵敏度和特异度分别为0.682和0.754及0.673和0.634,在验证集则分别为0.667和0.806及0.644和0.619;在HBeAg阴性患者,训练集血清HBV DNA载量有预测显著炎症和显著纤维化的效能,其ROC曲线下面积分别为0.629和0.671。基于Youden指数确定的血清HBV DNA预测显著炎症和显著纤维化的最佳截断点为≥4.315×104 IU/ml和≥2.748×103 IU/ml,在训练集其对应的灵敏度和特异度分别为0.444和0.606及0.795和0.717,在验证集则分别为0.446和0.613及0.797和0.622。结论血清HBsAg水平对HBeAg阳性患者的严重纤维化和进展期纤维化有显著的预测价值,而血清HBV DNA载量对HBeAg阴性患者的显著炎症和显著纤维化有一定的预测意义。

关键词: 慢性乙型肝炎, 乙型肝炎病毒表面抗原, 乙型肝炎病毒DNA, 肝纤维化, 无创诊断

Abstract: Objective To evaluate the efficacies of serum HBsAg levels and HBV DNA loads in prediction of hepatic histological activity grading and fibrosis staging in patients with chronic hepatitis B. Methods 740 patients with CHB were randomly divided into training set and validation set. 281 were HBeAg-positive,and 169 HBeAg-negative in training set,and 170 were HBeAg-positive,and 120 HBeAg-negative in validation set. Liver biopsies were performed,and histological activity grading and fibrosis staging ≥G2 and ≥S2,≥G3 and ≥S3, and ≥G4 and ≥S4 were respectively defined as significant inflammation and significant fibrosis, severe inflammation and severe fibrosis,and advanced inflammation and advanced fibrosis. Serum HBsAg was measured by Abbott Architect I2000,and serum HBV DNA was assayed by real-time PCR. Results In HBeAg-positive patients,the efficiencies of serum HBsAg levels for prediction of severe fibrosis and advanced fibrosis achieved moderate levels in training set,and the areas under ROC curves were 0.707 and 0.726, respectively; the optimal cut-off-value of serum HBsAg levels as determined by Youden indexes for prediction of severe fibrosis and advanced fibrosis were ≤6.683×103 IU/mL and ≤6.427×103 IU/mL,and the corresponding sensitivities and specificities in training set were 0.682 and 0.754,and 0.673 and 0.634,respectively,and those in validation set were 0.667 and 0.806,and 0.644 and 0.619,respectively;In HBeAg-negative patients,the efficiencies of serum HBV DNA loads for prediction of significant inflammation and significant fibrosis were significant,and the areas under ROC curves were 0.629 and 0.671,respectively;the optimal cut-off-value of serum HBV DNA levels as determined by Youden indexes for prediction of significant inflammation and significant fibrosis were ≥4.315×104 IU/mL and ≥2.748×103 IU/mL,respectively,and the corresponding sensitivities and specificities in training set were 0.444 and 0.606,and 0.795 and 0.717,respectively,and those in validation set were 0.446 and 0.613,and 0.797 and 0.622,respectively. Conclusions Serum HBsAg levels in HBeAg-positive patients with CHB have significant values for prediction of severe fibrosis and advanced fibrosis,and serum HBV DNA loads in HBeAg-negative patients have some hints of significant inflammation and significant fibrosis in liver tissues.

Key words: Hepatitis B, Hepatitis B viral surface antigen, Hepatitis B virus DNA, Quantitative measurement, Liver fibrosis, Noninvasive diagnosis