摘要
目的了解慢性乙型肝炎病毒(HBV)感染者抗病毒治疗前阿德福韦酯(ADV)相关位点预存病毒变异的发生情况以及临床特点。方法采用基因测序的方法对211例拟行抗病毒治疗的慢性HBV感染者的血清样本进行P区病毒基因测序,同时检测HBV基因型、HBV血清学标志物、HBV DNA等。依据病毒检测结果分为预存病毒变异组和无变异组。结果 211例慢性HBV感染者中,检测出ADV预存病毒变异9例(4.27%),其中4例有不规范的核苷(酸)类似物用药史(ADV除外),变异位点以rtN238T为主(44.44%),且以多个位点变异(55.56%)、完全变异株和野生株共存(88.89%)为主;预存病毒变异组中男性及终末期肝病的构成比均高于无变异组(P<0.05,P<0.001);预存病毒变异组的年龄为(45.9±10.5)岁,无变异组为(35.6±10.2)岁(t=2.978,P=0.003);两组的HBV基因型构成、E抗原阳性状态及HBV DNA水平比较差异均无统计学意义。结论在未经ADV抗病毒治疗的慢性HBV感染者中存在ADV相关位点预存病毒变异,并可能与患者不规范应用抗病毒药物有关;HBV感染史较长、病情持续进展以及男性患者易出现ADV相关位点预存病毒变异;患者应该接受和执行规范的抗病毒治疗,以达到预防病毒变异,从而避免挽救治疗。
Objective To understand the pathogenic and clinical characteristics of HBV pre-existing mutations related to ADV among ADV treatment-naive patients with chronic HBV infection.Methods The gene resistance mutations of HBV P region in 211 ADV treatment-naive patients were analyzed by gene sequencing,meanwhile the HBV genotypes as well as HBV serum markers and HBV DNA levels were also determined.All patients were divided into pre-existing mutation group and non-mutation group based on the above data.Results Out of 211 patients,9 were found to have pre-existing mutations related to ADV and 4 of them had ill-formed usage of other antiviral drugs except for ADV.rtN238T mutation was found to be the dominant one（44.44%）,and multi-sites mutation（55.56%） and mutation co-existence with wild strain（88.89%） were also popular.The constituent ratios of males and end-stage liver diseases in pre-existing mutation group were higher than those in non-mutation group（P=0.013,〈0.001）.The average age of patients was 45.9±10.5 years in pre-existing mutation group and 35.6±10.2 years old in non-mutation group（t=2.978,P= 0.003）.There were no statistically significant differences of constituent ratio of HBeAg,HBV genotypes and HBV DNA levels between the two groups.Conclusions There may be some cases with pre-existing mutations in ADV treatment-naive patients,and these pre-existing mutations may be related to ill-formed usage of antiviral drugs.Male patients and patients with longer history of HBV infection are more likely to have pre-exist mutations.It is important for patients to accept normative antiviral treatment in order to prevent resistance and avoid salvage therapy.
出处
《中国预防医学杂志》
CAS
2013年第1期39-42,共4页
Chinese Preventive Medicine
基金
浙江省医药卫生科学研究基金(2008B167)
宁波市优秀中青年卫生技术人才资助项目(甬卫发2011-145号)
宁波市领军和拔尖人才培养工程资助项目[甬人社发﹝2012﹞131号]
关键词
肝炎病毒
乙型
预存病毒变异
基因测序
阿德福韦酯
Hepatitis B virus
Pre-existing resistance mutation
Gene sequencing
Adefovir dipivoxil
