慢性HBV感染者抗病毒治疗前HBV基本核心启动子及前C区突变的检测及意义  

The prevalence and significance of HBV basic core promoter /precore mutations in untreated chronic hepatitis B patients

作　　者：郑金鑫[1] 于敏[1] 席宏丽[1] 郑颖颖[1] 尹胜杰[1] 张独佾[1] 王芳[1] 曾争[1] 于岩岩[1] 

机构地区：[1]北京大学第一医院感染疾病科,北京100034

出　　处：《临床肝胆病杂志》2011年第3期286-288,共3页Journal of Clinical Hepatology

基　　金：国家自然科学基金资助项目(NO.30671855);美国国家癌症研究所(NCI)资助项目(N01-CO-12400);国家"十一五"重大科技专项资助项目(2008ZX10002004)

摘　　要：目的研究慢性乙型肝炎病毒(HBV)感染者抗病毒治疗前HBV基本核心启动子(BCP)突变和前C区(PreC)突变与HBeAg、HBV DNA水平和慢性肝病进展的关系。方法收集283例慢性HBV感染者抗病毒治疗前的血清标本,其中慢性乙型肝炎(CHB)185例,肝硬化(LC)98例。采用PCR后直接测序法检测HBV BCP和PreC区突变,同时确定基因型。结果在HBeAg阴性和HBeAg阳性CHB患者中,前C区A1896变异率分别为44.6%(37/83)和21.6%(22/102)(χ2=11.154,P=0.001),LC患者分别为43.4%(23/53)和17.0%(8/47)(χ2=8.101,P=0.004)。在HBeAg阳性患者中,BCP T1762/A1764双突变率LC组和CHB组分别为89.4%(42/47)和70.6%(72/102)(χ2=6.310,P=0.012)。在单变量分析中,只有年龄(≥45岁)(χ2=27.861,P<0.001)、BCP T1762/A1764双突变(χ2=8.675,P=0.003)和HBV DNA(≥105拷贝/ml)(χ2=20.499,P<0.001)与LC进展有关。多因素Logistic回归分析(匹配年龄和性别)发现,BCP T1762/A1764双突变(OR=3.260,95%CI:1.401～7.586;wald=7.517,P=0.006)和HBV DNA(≥105拷贝/ml)(OR=4.640,95%CI:2.331～9.237;wald=19.089,P<0.001)是LC进展的危险因素。结论前C区A1896突变与HBeAg的消失有关;年龄(≥45岁)、BCP T1762/A1764双突变和HBV DNA高载量(≥105拷贝/ml)与肝硬化进展有关。Objective To study the association of hepatitis B virus（HBV） basic core promoter（BCP）/precore（Pre C） mutations with the HBeAg,HBV DNA level and the progression of liver disease.Methods 283 untreated HBV patients were divided into 2 groups： chronic hepatitis B group with 185 patients（CHB,185） and liver cirrhosis group with 98 patients（LC,98）.HBV BCP and PreC mutations and genotypes were determined by direct sequencing.Results Precore（A1896） mutation was higher in HBeAg negative than that in HBeAg positive patients in CHB [44.6%（37/83）vs 21.6%（22/102）,χ2=11.154,P=0.001] and LC [43.4%（23/53）vs 17.0%（8/47）,χ2=8.101,P=0.004],respectively.Among HBeAg positive patients,BCP dual mutations（T1762/A1764） were more common in LC patients than that in CHB patients [89.4%（42/47）vs 70.6%（72/102）,χ2=6.310,P=0.012].In univariant analysis,age（≥45 years）（χ2=27.861, P0.001）,BCP T1762/A1764 mutations（χ2=8.675,P=0.003） and HBV DNA（≥105 copies/ml）（χ2=20.499,P0.001） were associated with the progression of LC.Multivariate logistic regression analysis（adjusted for age and gender） revealed that BCP T1762/A1764 mutations（OR=3.260,95% CI：1.401～7.586;wald=7.517,P=0.006） and HBV DNA（≥105 copies/ml）（OR=4.640,95% CI：2.331～9.237;wald=19.089,P0.001） were independently associated with the LC development.Conclusion PreC mutation（A1896） was associated with HBeAg loss.Age（≥45years）,T1762/A1764 mutations,HBV DNA（≥105 copies/ml）were risk factors for LC progression.

关 键 词：肝炎病毒 乙型 基因 病毒 突变 肝炎 乙型 慢性 肝硬化 

分 类 号：R512.62[医药卫生—内科学]