自然变异与干扰素诱导变异中HBV突变位点的规律及HBV突变与抗病毒药物关系研究

发布时间：2019-01-01 21:52

【摘要】：目的比较HBV-BCP区/前C/C区自然变异者与干扰素诱导变异者变异位点的规律，进而初步分析是否存在特定的干扰素诱导突变位点；探讨普通干扰素和拉米夫定在HBV-BCP区/前C/C区自然突变者中的短期抗病毒疗效；探讨普通干扰素诱导的HBV-BCP区/前C/C区突变者序贯应用聚乙二醇干扰素和拉米夫定序贯抗病毒治疗的短期疗效。方法采用回顾性队列研究，病例来自于郑州大学第一附属医院感染科门诊的104例检测出HBV-C基因区段（C基因启动子（BCP）/前C/C基因）突变的HBeAg阴性的慢性乙型肝炎（CHB-e）患者，据突变前有无干扰素治疗史分为自然变异组(A组，60例)和干扰素诱导变异组（B组，44例），通过分析两组突变位点的规律，进一步确定HBV-C基因区段是否存在干扰素诱导的特点突变位点；A组根据抗病毒药物的选择分为普通干扰素组（A1组，32例）和拉米夫定组（A2组，28例），检测两组抗病毒治疗6个月后的ALT、HBV-DNA水平；B组停用普通干扰素，根据其再次抗病毒药物的选择分为聚乙二醇干扰素组（B1组，共16例）和拉米夫定组（B2组，共28例），检测两组抗病毒治疗6个月后的ALT、HBV-DNA水平。结果 1．60例HBV自然变异者（A组）与44例干扰素诱导变异者（B组）相比，前C区G1896A位点在两组的突变率分别为73.33%和68.18%，两组差异无统计学意义（P0.05）；BCP区双位点（A1762T并G1764A）在两组的突变率分别为71.67%和65.90%，两组差异无统计学意义（P0.05）；C基因区热点突变位点（I97L、S87G、L60V）的突变率在B组明显高于A组，差异有统计学意义（P0.05）。 2．A组60例自然变异者中32例（A1组）和28例（A2组）分别接受普通干扰素和拉米夫定抗病毒治疗6个月后，ALT复常率分别为90.63%和93.75%，两组差异无统计学意义（P0.05）；HBV-DNA阴转率分别为96.43%和100%，且差异无统计学意义（P0.05）。 3．B组44例普通干扰素诱导变异者均停用普通干扰素干扰素，其中B1组（16例）和B2组（28例）分别接受聚乙二醇干扰素和拉米夫定序贯抗病毒治疗6个月后，两组ALT复常率分别为31.25%和75.00%，，B2组明显高于B1组且差异有统计学意义（P＜0.05）；两组HBV-DNA阴转率分别为37.50%和82.14%，B2组明显高于B1组且差异有统计学意义。结论 1．HBV-BCP区/前C/C区自然变异者与干扰素诱导变异者前C区G1896A位点及BCP区A1762T并G1764A双位点均有较高的突变率，但两组无明显差异，C基因区热点突变位点（I97L、S87G、L60V）在干扰素诱导突变组明显高于自然变异组，我们推测C基因区热点突变位点（I97L、S87G、L60V）可能是干扰素持续作用后的特定突变位点。 2．HBV-BCP区/前C/C区自然变异者，干扰素和拉米夫定的近期应答率均较高且无明显差异。 3．普通干扰素诱导HBV-BCP区/前C/C区变异者,应用拉米夫定序贯抗病毒治疗较聚乙二醇干扰素效果好。
[Abstract]:Objective to compare the mutation sites of HBV-BCP / former C / C region with those induced by interferon, and to analyze the existence of specific IFN- induced mutation sites. To investigate the short-term antiviral efficacy of interferon and lamivudine in HBV-BCP / pre-C / C mutants. Objective: to investigate the short-term efficacy of HBV-BCP / pre-C region mutation induced by common interferon in patients with sequential application of pegylated interferon and lamivudine sequentially antiviral therapy. Methods A retrospective cohort study was used. The cases were from 104 chronic hepatitis B (CHB-e) patients with HBeAg negative mutations in the HBV-C gene region (BCP) / ex-C gene) detected in the Department of Nosocomial infection, first affiliated Hospital, Zhengzhou University. According to the history of interferon therapy before mutation, they were divided into natural mutation group (group A, n = 60) and interferon induced mutation group (group B, n = 44). It was further determined whether there were characteristic mutation sites induced by interferon in the HBV-C gene region. Group A was divided into normal interferon group (group A1, 32 cases) and lamivudine group (group A2, 28 cases) according to the choice of antiviral drugs. Group B stopped using common interferon. According to its choice of antiviral drugs, it was divided into two groups: polyethylene glycol interferon group (group B1, n = 16) and lamivudine group (group B2, n = 28). The ALT, of two groups after 6 months of antiviral therapy was detected. HBV-DNA level. Results 1.The mutation rates of G1896A locus in precore C region were 73.33% and 68.18% in group A and group B, respectively, compared with those in group B induced by interferon in 60 cases (group A), and in group B (group B), the mutation rates of G1896A locus were 73.33% and 68.18%, respectively. There was no significant difference between the two groups (P0.05). The mutation rates of two loci of BCP (A1762T and G1764A) in the two groups were 71.67% and 65.90, respectively. There was no significant difference between the two groups (P0.05). The mutation rate of C gene hot spot locus (I97LX S87GG L60V) in group B was significantly higher than that in group A (P0.05). 2. In group A, 32 cases (A1 group) and 28 cases (A2 group) were treated with common interferon and lamivudine antiviral therapy for 6 months respectively. The normal rates of ALT were 90.63% and 93.75%, respectively. There was no significant difference between the two groups (P0.05). The negative conversion rate of HBV-DNA was 96.43% and 100%, respectively, and the difference was not statistically significant (P0.05). 3. In group B, all 44 normal interferon induced variants were stopped. Group B1 (16 cases) and group B2 (28 cases) were treated with PEG-interferon and lamivudine sequential antiviral therapy for 6 months, respectively. The recovery rate of ALT in the two groups was 31.25% and 75.00%, respectively, which was significantly higher than that in the B1 group (P < 0. 05). The negative conversion rate of HBV-DNA in the two groups was 37.50% and 82.14%, respectively, which was significantly higher than that in the B1 group. Conclusion the G1896A locus of preC region and the double locus of A1762T and G1764A of BCP region in 1.HBV-BCP / pre C / C region mutation group and interferon induced mutation group have high mutation rate, but there is no significant difference between the two groups, and there is no significant difference between the two groups, and there is no significant difference between the two groups, and there is no significant difference between the two groups, and there is no significant difference between the two groups. S87Gfl60V) was significantly higher in interferon induced mutation group than that in natural mutation group. We speculated that the hot spot mutation site of C gene region (I97LX S87GFL60V) might be a specific mutation site after continuous interferon treatment. The short-term response rates of interferon and lamivudine in 2.HBV-BCP / pre C / C region natural variants were higher than those in Lamivudine. 3. The effect of lamivudine sequential antiviral therapy was better than that of pegylated interferon in inducing HBV-BCP / pre C / C region mutation by common interferon.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R512.62

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