乙型肝炎病毒基因型、基础核心启动子和C区变异与干扰素疗效的观察  

The association between hepatits B virus genotype, the mutations in the basic core gene promoter, pre C/ C region and the treatment response to interferon α-lb

作　　者：董菁[1] 董晓雯[2] 张苏华[3] 林国贤 苏智军[5] 刘家俊[6] 孙家敏[7] 陈攸涛[1] 陈靖[1] 江家骥[1] 

机构地区：[1]福建医科大学附属第一医院肝病中心,福州 350005 [2]福建医科大学附属协和医院高干科,福州 350005 [3]福建医科大学附属闽东医院感染科,福州 350005 [4]福建莆田医学院附属医院感染科,福州 350005 [5]福建医科大学附属泉州第一医院感染科,福州 350005 [6]厦门大学附属第一医院肝病中心 [7]龙岩市第二医院感染科

出　　处：《中华传染病杂志》2011年第1期21-25,共5页Chinese Journal of Infectious Diseases

基　　金：福建省教育厅教授发展基金课题项目（JS06053）

摘　　要：目的探讨HBV基因型、基础核心启动子（BCP）和C区变异与IFNa抗病毒疗效的相关性。方法选择IFNa-1b治疗6个月的HBeAg阳性慢性乙型肝炎（CHB）患者，随访6个月。应用限制性片段长度多态性（RFLP）法检测HBV基因型，PCR测定BCP、前c／c区核苷酸序列。计量资料采用t检验、方差分析，计数资料采用卡方检验、Fisher确切概率法，并进行多因素条件Logistic回归分析。结果共39例CHB患者完成观察，治疗结束时，应答16例，占41．0％；随访结束时，应答者中持续应答12例，占30．8％，复发4例，占10．3％。其中B基因型29例，占74．4％，c基因型10例，占25．6％。基因型型别差异与IFNd-1b疗效无关。8例患者BCP区T1762／A1764双变异，占20．5％，与IFNa—lb疗效无相关。8例患者检出A1896变异，占20．5％，随访结束时获得疗效的3例A1896变异株感染者均复发。C区非淋巴细胞表位测序发现，15例患者L60V变异，占38．5％，14例为197I。变异，占35．9％。与60V比较，表现为60L的患者在随访结束时的HBeAg血清学转换率和HBVDNA阴转率明显低（Fisher确切概率法，P：0．0126、0．0069）。与97L比较，表现为97I的患者在治疗结束时和随访结束时的HBVDNA阴转率明显低（Fisher确切概率法，P-0．0484、0．0024）。Logistic回归分析显示，基因型、C区变异与IFNa-lb疗效无相关。结论HBV基因型、BCP双变异与IFNa的疗效无关，c区非淋巴细胞表位L60V及197L变异可能有利于IFNa的治疗。Objective To investigate the association between hepatitis B virus （HBV） genotype, the mutations in HBV basic core gene promoter（BCP）, pre C/C gene region and treatment response to interferon （IFN）a-lb. Methods Hepatitis B e antigen （HBeAg） positive chronic hepatitis B （CHB） patients were treated with IFNa lb for 6 months and were followed up for 6 months after the end of treatment. Restriction Fragment Length Polymorphism （RFLP） was used for determining HBV genotype. HBV DNA was amplified by polymerase chain reaction （PCR） and analyzed for BCP and pre C/C gene region by sequencing. Measurement data were compared using t test and analysis ofvariance. Enumeration data were compared using chi-square test, Fisher exact probability test. Logistic regression analysis was utilized for multi-factor analysis. Results There were 39 patients who completed the treatment and follow up in this study. At the end of treatment, 16 （41.0%） patients showed response to the IFNa lb treatment. At the end of follow up, four out of 16 patients who achieved on treatment response relapsed. Among 3a patients, 29（74.4% ） were infected with genotype B and 10（25. 6%） with genotype C. The treatment response rates were not significant different between the groups with different genotypes. The double mutation pattern （T1762/A1764） was found in eight （20. 5%） patients. The response rates to IFNa-lb treatment were not significant different between the group with and without double mutation pattern. A1896 mutation was detected in eight patients at baseline. Three of them became HBeAg negative at the end of treatment and returned to HBeAg positive during follow-up. The non-lyphocyte epitope mutations, L60V and I97L, were found in 15 patients （38.5~） and 14 patients （35.9%）, respectively. At the end of followup, the patients with 60V had a significantly lower HBeAg seroconversion rate and HBV DNA undetectable rate compared to the patients with 60L （Fisher exact probability test; P = 0. 0126 a

关 键 词：肝炎病毒 乙型 变异(遗传学) 基因型 干扰素-A 启动区(遗传学) 

分 类 号：R51[医药卫生—内科学]