隐匿性乙型肝炎患者乙肝病毒preS／S基因突变分析  

A study on sequence variations in preS/S regions of hepatitis B virus in occult infective patients

作　　者：吴蓓颖[1] 蔡刚[1] 林佳菲[1] 陆秋涯[1] 李琳[1] 樊绮诗[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院检验科,200025

出　　处：《中华微生物学和免疫学杂志》2011年第8期724-728,共5页Chinese Journal of Microbiology and Immunology

摘　　要：目的隐匿性乙肝感染与严重慢性肝损伤的病毒学与免疫学机制尚未完全阐明，拟通过研究隐匿性HBVpreS／S区基因变异，初步揭示隐匿性乙肝发生及其致慢性严重肝损伤的病毒学因素。方法收集瑞金医院门诊及住院HBsAg阴性患者的血清，抽提DNA，利用巢式PCR方法对隐匿性感染进行检测；克隆阳性标本的preS／S区全长基因并测序分析，探讨其突变类型与严重慢性肝损伤的关系。结果在全部468份HBsAg阴性血清中共检出隐匿性HBV感染69例，HBcAb单独强阳性组、HBeAb单独强阳性组、HBeAg单独阳性组、HBcAb与HBsAb同时强阳性组和5项指标全阴性组的检出率分别为16％、8．7％、36．4％、18．3％和0％。隐匿性感染患者血清HBV．DNA水平明显低于HBsAg阳性感染患者，隐匿性HBVpreS／S区缺失突变、preS2基因M1I和Q2K突变，S基因Q129N／R／P、G185R和S210R突变的频率明显高于HBsAg阳性组。伴严重肝损伤的隐匿性感染较无严重肝损伤隐匿性感染患者在性别比例及血清HBV—DNA水平方面均有明显差异。伴严重肝损伤的隐匿性感染的HBV在preS2基因MII和Q2K，S基因G185R和S210R的突变频率明显高于无严重肝损伤者，但preS缺失和s基因Q129N／R／P的突变频率低于无严重肝损伤者。以伴严重肝损伤的隐匿性感染与HBsAg阳性严重肝损伤者相比，后者HBV—DNA水平明显高于前者，但preS2基因MII和Q2K、S基因G185R和S210R突变的频率明显低于前者。结论隐匿性感染与HBsAg阳性病人之间致慢性严重肝损伤的病毒学因素存在不同；preS2区MII和Q2K以及s区G185R和S210R等突变对于隐匿性乙肝患者而言，可能是评价其是否进展为严重慢性肝损伤的有用指标。Objective To assess the sequence variations in preS/S regions of occult hepatitis B virus （OHB） and their relationship to severe chronic hepatic injury. Methods We collected samples from HBsAg negative patients, and evaluated their HBV-DNA by nest-PCR. HBV-DNA positive samples were used for analysis of preS/S region by PCR sequencing. Results Sixty-nine cases with HBV-DNA were identified in 468 cases without HBsAg. The positive percents were 16%, 8.7%, 36.4%, 18.3% and 0% in group of only HBcAb positive, only HBeAb positive, only HBeAg positive, both HBcAb and HBsAb positive and all indexes negative, respectively. The level of HBV-DNA of OHB was significant lower than that in HBsAg positive patients. Compared with HBsAg positive controls, preS/S deletion, MII and Q2K in preS2 region, Q129N/R/P,G185R and S210R in S region were more common in OHB. Moreover, MII and Q2K in preS2 region, G185R and S210R in S region in OHB with severe chronic hepatic injury were more com- mon that those in OHB without severe chronic hepatic injury. Compared with HBsAg positive patients with severe chronic hepatic injury, the level of HBV-DNA was lower, while the frequency of MII and Q2K mutation in preS2 region, G185R and S210R in S region were more common in OHB patients with severe chronic hepatic injury. Conclusion The virological factors were different between OHB and HBsAg positive pa- tients. The MII and Q2K in preS2 region, G185R and S210R in S region might be useful for prognosis eval- uation of OHB patients.

关 键 词：乙型肝炎病毒 前S/S基因 突变分析 肝损害 

分 类 号：R51[医药卫生—内科学]