摘要
目的分析大样本肝病人群中隐匿性HBV感染(OBI)检出率及其HBV S基因主要亲水区(MHR)免疫逃逸突变特点。方法回顾性收集2007年7月-2011年8月就诊于解放军302医院的11 650例肝病患者的临床资料和基因测序数据,分析OBI检出率及HBV S基因MHR免疫逃逸突变,并与不同滴度HBsAg的慢性乙型肝炎(CHB)患者的MHR突变对比。结果在6996例检测了血清HBsAg的肝病患者中共筛选出12例OBI患者(即血清HBsAg阴性且HBV DNA阳性),OBI检出率为0.172%(12/6996)。8例OBI患者HBV S基因直接测序成功,其中6例(75%,6/8)检出10种MHR突变,包括经典突变sG145R在内的9种已报道的OBI相关MHR突变。低滴度和中高滴度HBsAg两组CHB患者的主要MHR突变为sL110I、sT113S、sS143T、sR160K和sF161Y,除sS143T外均不是已报道且公认的OBI相关突变。结论本研究通过临床大样本分析显示肝病患者中有较高的OBI检出率,且多数患者可检出OBI相关MHR免疫逃逸突变,提示这些突变与OBI发生密切相关。
Objective To analyze the detection rate of occult HBV infection（OBI） and the characteristics of immune escape mutation in major hydrophilic region（MHR） of HBV S-gene with a large sample of liver diseases. Methods The clinical and genetic sequencing data of 11,650 patients with liver diseases admitted in Beijing 302 Hospital from July 2007 to August 2011 were retrospectively collected. The detection rate of OBI and the immune escape mutation in MHR of HBV S-gene were analyzed, and then compared with those in chronic hepatitis B（CHB） patients with different HBsAg levels. Results Twelve OBI patients with negative serum HBsAg level and positive HBV DNA level were screened from 6,996 patients with HBsAg quantitation, the detection rate of OBI was 0.172%（12/6,996）. HBV S gene was sequenced successfully in 8 OBI patients. Ten MHR associated immune-escape mutations were detected in 6 OBI patients, and 9 mutations among them were well documented to be OBI-associated mutations including classical mutation s G145 R. W hile, the main MHR mutations were sL110I, sT113S, sS143T, sR160K and sF161Y in both CHB patient groups with low-and medium to high-titers of HBsAg, and these mutations were not recognized OBI-related mutations except s S143 T. Conclusion The findings of present paper show a high detection rate of OBI in a large clinical sample of patients with liver diseases, and most OBI patients harbor OBI associated MHR immune escape mutation, indicating these mutations are closely associated with OBI occurrence.
作者
张凯
徐东平
陈容娟
赵丽
刘璐洁
林亚云
李奇
思兰兰
李晓东
李进
蔺淑梅
刘妍
ZHANG Kai;XU Dong-ping;CHEN Rong-juan;ZHAO Li;LIU Lu-jie;LIN Ya-yun;LI Qi;SI Lan-lan;LI Xiaodong;LI Jin;LIN Shu-mei;LIU Yan(Viral Hepatitis Research Laboratory, Institute of Infectious Diseases and Research Center for Clinical and Translational Medicine, 302 Hospital of PLA, Beijing 100039, China;Department of Infectious Diseases, the First Affiliated Hospital of Xi＇an Jiaotong University, Xihn 710061, China)
出处
《解放军医学杂志》
CAS
CSCD
北大核心
2018年第5期380-385,共6页
Medical Journal of Chinese People's Liberation Army
基金
国家自然科学基金面上项目(81572010
81373136)
北京市自然科学基金面上项目(7172206)
首都卫生发展科研专项自主创新项目(2016-2-5032)~~
关键词
乙型肝炎病毒
隐匿性感染
病毒突变
主要亲水区
免疫逃逸
hepatitis B virus
occult infection
viral mutation
major hydrophilic region
immune escape
