慢性乙型肝炎HBsAg及HBsAg/HBV DNA比值与组织病理炎症活动度的相关性

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

目的 研究HBeAg阳性慢性乙型肝炎（CHB）基线血清HBsAg、HBsAg/HBVDNA比值与肝组织病理炎症活动度的相关性. 方法 回顾性分析153例HBeAg阳性CHB患者基线HBsAg、HBsAg/HBV DNA比值与肝组织病理炎症活动度的相关性.采用Taqman荧光定量PCR法检测血清HBV DNA水平,定量检测血清HBsAg滴度. 结果 HBsAg （log10IU/ml）与HBV DNA （log10IU/ml）、HBsAg/HBV DNA比值进行相关性分析,相关系数r分别为0.642、0.57,P值均＜ 0.0001,均呈显著性正相关;HBsAg和HBsAg/HBV DNA比值与炎症活动度进行相关性分析,相关系数r分别为-0.389、-0.307,P值均＜0.0001,二者与炎症活动度均呈负相关;而ALT （log10U/L）与炎症活动度呈正相关（r=0.480,P＜0.0001）.肝组织炎症活动度中度及以上患者的血清HBsAg及HBsAg/HBV DNA比值均显著低于轻度及以下患者,组间差异具有统计学意义（P均＜ 0.01）.HBsAg、HBsAg/HBV DNA比值及ALT在组织炎症活动度最优截断点的受试者工作曲线下面积分别为0.700、0.672、0.713;当机会曲线下面积等于0.5时,其显著性水平均有统计学意义（P均＜0.001）.HBsAg诊断组织炎症活动度的灵敏度为76.92％高于ALT的4.36％;HBsAg/HBV DNA比值的特异度为81.33％高于ALT的64.00％,ALT的约登指数均高于HBsAg及HBsAg/HBV DNA比值.当HBsAg与ALT并联时,其灵敏度高达94.08％;串联时,其特异度可高达85.60％. 结论 HBeAg抗原阳性CHB患者HBsAg、HBsAg/HBV DNA比值及ALT均可作为肝组织炎症程度的判断指标,HBsAg与ALT并联或串联诊断时具有更高的灵敏度和特异度.

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 ＜ 0.0001）.A significant positive correlation （r =0.642,P ＜ 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 ＜ 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 ＜ 0.0001）.Patients with G ＜ 2 necroinflammation had significantly higher HBsAg titre and HBsAg/HBV DNA ratio than patients with G ≥ 2 necroinflarnmation （both P ＜ 0.01） but similar levels ofHBV DNA.Generation of a receiver operating characteristic curve using G ≥ 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 （P＜ 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.