乙肝病毒前C基因区1896位点变异的临床研究

发布时间：2018-05-14 14:44

本文选题：乙型肝炎病毒 + 前C基因区　；参考：《大连医科大学》2007年硕士论文

【摘要】： 乙型肝炎的治疗目前仍是医学的一大难题。目前,对乙肝患者病情变化及治疗效果监测的实验室指标多为血清免疫学指标、肝功能及病毒DNA载量作为主要指标,然而,这些项目难以解释血清免疫学指标好转而实际上患者病情并未缓解,或者免疫学指标与生化学指标、病毒载量不一致的情况,无法满足临床治疗的需要。乙肝病毒(HBV)前C基因区1896位点(nt1896)的变异是较常见的变异,HBV变异后对乙肝诊断、治疗、预防都产生重大影响。目的:了解HBsAg(+)/HBeAb(+)/HBcAb(+)和HBsAg(+)/HBeAg(+) /HBcAb(+)的慢性乙肝病人血清HBV DNA前C基因区nt1896的变异情况及其与HBV DNA水平及转氨酶(ALT)关系。方法:将所有的实验对象分为HBsAg(+)/HBeAb(+)/HBcAb(+)组和HBsAg(+)/HBeAg(+)/HBcAb(+)组,分别检测肝功能指标,进一步根据ALT分组。用免疫荧光PCR法定量检测HBV DNA并用聚合酶链反应杂交(PCR—ELISA)检测HBV前C区nt1896位点的变异情况。用χ~2检验进行统计学分析,P0.05被认为有差异。结果:172例患者中有89例HBV DNA阳性,其中58例发生nt1896位点变异,变异率为65.2%(58/89)。HBsAg(+)/HBeAg(+)/HBcAb组的106例中,血清HBV DNA阳性64例,阳性率60.4%,平均浓度1.46×10~7(2.15×10~3—5.0×10~7)拷贝/ml , nt1896变异40例,变异率为62.5%(40/64)。HBsAg(+)/HBeAb(+)/HBcAb组的66例中, HBV DNA阳性25例,阳性率37.9%,平均浓度3.01×10~6(1.10×10~3—5.0×10~7)拷贝/ml。nt1896变异18例,变异率为72.0%(18/25)。经统计分析,两组HBV DNA阳性率有显著差异, nt1896位变异率无显著差异。根据ALT范围进一步分组发现,在HBsAg(+)/HBeAb(+)/HBcAb(+)患者中ALT升高组(40U/L)DNA(+)的15例全部发生变异,变异率100%,而ALT正常组HBV DNA(+)的10例中只有3例发生变异,变异率30%(3/10),两组间P0.05。结论:HBsAg(+)/HBeAg(+)/HBcAb(+)和HBsAg(+)/HBeAb(+) /HBcAb(+)慢性乙型肝炎病人都存在较高的前C区nt1896变异率( P0.05)。前C区A1896变异可能是影响HBV DNA复制的一个因素,尤其对HBsAg(+)/HBeAb(+)/HBcAb(+)的乙肝病人,前C区变异阳性者比无前C区变异者伴有更高水平的HBV DNA。
[Abstract]:The treatment of hepatitis B is still a big problem in medicine. At present, the laboratory indexes for monitoring the state of illness and therapeutic effect of hepatitis B patients are mostly serum immunological indexes, liver function and viral DNA load are the main indexes, however, These items are difficult to explain the improvement of serum immunological indicators but in fact the patient's condition has not been alleviated or the immunological index is inconsistent with the biochemical index and the viral load can not meet the need of clinical treatment. The mutation of 1896 locus nt1896 in the preC region of hepatitis B virus (HBV) is a common mutation which has a great influence on the diagnosis, treatment and prevention of HBV. Objective: to investigate the variation of serum nt1896 in serum of chronic hepatitis B patients with HBs / HBeAb (/ HBeAb) and / HBeAg (+ / HBeAg () / HBcAbs) and their relationship with HBV DNA level and alt. Methods: all the subjects were divided into two groups: HBsAg (/ HBeAb) group and HBsAg (/ HBeAg (/ HBeAg) group). Liver function indexes were measured and further grouped according to ALT. HBV DNA was quantitatively detected by immunofluorescence PCR assay and PCR-ELISA-PCR was used to detect the variation of nt1896 locus in HBV precore region. Statistical analysis with 蠂 2 test was considered to be different. Results of the 172 patients, 89 were HBV DNA positive, 58 of them had nt1896 site mutation, and the variation rate was 65.2g / 58 / 89 路HBsAg (64 of 106 cases in the HBeAg / HBcAb group), the positive rate was 60.44.The average concentration was 1.46 脳 102.15 脳 103-5.0 脳 10 ~ (7) copies / ml, and the nt1896 mutation was 40 / ml, respectively, and the mean concentration was 1.46 脳 102.15 脳 103-5.0 脳 10 ~ (7) / ml, and the mean concentration was 1.46 脳 102.15 脳 10 ~ (3) ~ 5.0 脳 10 ~ (7) / ml. The variation rate was 62.5% 40 / 64 路HBsAg (25 out of 66 cases in the / HBeAb group, 37.9%, mean concentration 3.01 脳 101.10 脳 101.10 脳 101.10 脳 10 ~ (7) / ml. Nt1896 (n = 18 / 25). Statistical analysis showed that there was significant difference in HBV DNA positive rate between the two groups, but there was no significant difference in nt1896 site variation rate between the two groups. According to the range of ALT, 15 of the patients with elevated ALT in 40 U / L ALT (/ HBeAb) had all mutated, the mutation rate was 100%, but only 3 out of 10 cases of HBV DNA() in the normal ALT group had mutation, with a variation rate of 30% / 10%, between the two groups (P0.05). Conclusion there is a high preC-region nt1896 mutation rate (P0.05) in patients with chronic hepatitis B, including:% HBeAg (/ HBeAg) and HBeAb / HBcAb (+ / HBeAb) / HBcAb.Conclusion there is a high preC-region nt1896 mutation rate (P0.05) in patients with chronic hepatitis B. Pre-C region A1896 mutation may be one of the factors affecting HBV DNA replication, especially in hepatitis B patients with HBsAg / HBeAb (P / HBeAb), preC-region mutation positive patients have higher levels of HBV DNA than those without pre-C mutation.
【学位授予单位】：大连医科大学
【学位级别】：硕士
【学位授予年份】：2007
【分类号】：R373

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