核心抗体阳性合格献血者隐匿性乙肝病毒感染分子生物学特性及追踪结果的研究  

Characterization and follow-up study of occult hepatitis B viral Infection in anti-HBc positive qualified blood donors

作　　者：叶贤林[1] 李彤[1] 孙淑君[1] 许晓绚[1] 杜鹏[1] 曾劲峰[1] 朱为刚[1] 杨宝成[1] 黎诚耀[2] Jean-Pierre Allain 

机构地区：[1]深圳市血液中心,广东深圳518035 [2]南方医科大学生物技术学院 [3]剑桥大学血液学系输血医学部

出　　处：《中国输血杂志》2016年第9期890-894,共5页Chinese Journal of Blood Transfusion

摘　　要：目的了解我国核心抗体阳性合格献血者隐匿性乙肝病毒感染(OBI)情况,分析血清学和分子生物性特征。方法对HBs Ag(-)、NAT检测无反应性的合格献血者血浆,进行乙肝两对半检测和anti-HBs定量检测,对核心抗体阳性标本进行病毒核酸提取,和BCP/PC区及S区巢式PCR扩增,对扩增结果阳性产物纯化后进行基因测序及序列分析,同时进行QPCR定量检测。对HBV DNA阳性的献血者进行追踪检测和分析。结果在1 033名合格献血者中,抗-HBc(+)占47.4%,阳性率随年龄的增长而增加(P<0.001),30岁以下年龄组为32.6%而到50岁以上年龄组为为69.8%。777/1033为抗-HBs(+),占75.2%。在抗-HBc(+)人群中共检出14例HBV DNA(+),其中7例抗-HBs滴度在100 IU/L以上,在抗-HBc(+)合格献血者中OBI阳性率为2.86%。8/14例OBI为B型,1例为C型。7/14能追踪的标本中,1例发现抗-HBe血清转换为阳性。所有追踪标本的病毒均变成检不出。5例BCP/PC区序列发生突变,3例S区氨基酸变异。结论经HBs Ag及NAT检测合格的抗-HBc(+)献血者,其血液中仍有一定几率含有HBV DNA,存在经输血传播病毒的威胁,提示在乙肝高流行地区需进一步提高核酸检测方法的灵敏度,必要时可增加抗-HBc的检测。Objective To evaluate the prevalence of occult HBV infection （OBI） among the anti-HBc positive qualified blood donors, and to analyze the serological and biological characteristics of hepatitis B virus. Methods Anti-HBc positive blood donations negative for HBsAg and HBV DNA were evaluated by standard NAT from Shenzhen for the presence of HBV DNA by sensitive nested PCR and QPCR. The titers of anti-HBs were quantified. The HBV DNA positive donors were followed up. Results Of the 1 033 qualified donors, 47.4% carried anti-HBc as evidence of exposure to HBV. Between different age groups, there was a steady increase in the anti-HBc positive rate, ranging from 32. 6% in the age group of less than 30 years to 69.8% in the age group of 〉 50 years （P 〈0. 001 ）. 777/1 033 （75.2%） carried anti-HBs （ 〉 10 IU/L）. HBV DNA was detected in 14 donors who were anti-HBc positive, HBsAg negative and routine NAT negative. Seven of those 14 specimens had anti-HBs titer above 100 mIU/ml. The prevalence of OBI in anti-HBc-positive qualified blood donors was 2. 86%. 8/14 OBI cases were genotype B and one was genotype C. Seven cases were followed up. One case converted to anti-HBe. In all traced samples, HBV DNA became undetectable. In five cases mutations in BCP/PC were found. In 3 cases, amino acid substitutions were found in S region. Conclusion A small proportion of anti-HBc positive qualified donors carry HBV DNA after HBsAg and NAT screening. This finding suggests the possibility of HBV transmission from asymptomatic donors, especially in areas of high HBV prevalence. More sensitive NAT rather than anti-HBc testing should be considered to improve blood safety.

关 键 词：献血者 隐匿性乙肝病毒感染 乙肝病毒核心抗体 HBV DNA 

分 类 号：R512.62[医药卫生—内科学] R446.6[医药卫生—临床医学]