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乙肝病毒前C基因區(qū)1896位點(diǎn)變異的臨床研究

發(fā)布時(shí)間:2018-05-14 14:44

  本文選題:乙型肝炎病毒 + 前C基因區(qū); 參考:《大連醫(yī)科大學(xué)》2007年碩士論文


【摘要】: 乙型肝炎的治療目前仍是醫(yī)學(xué)的一大難題。目前,對(duì)乙肝患者病情變化及治療效果監(jiān)測(cè)的實(shí)驗(yàn)室指標(biāo)多為血清免疫學(xué)指標(biāo)、肝功能及病毒DNA載量作為主要指標(biāo),然而,這些項(xiàng)目難以解釋血清免疫學(xué)指標(biāo)好轉(zhuǎn)而實(shí)際上患者病情并未緩解,或者免疫學(xué)指標(biāo)與生化學(xué)指標(biāo)、病毒載量不一致的情況,無(wú)法滿足臨床治療的需要。乙肝病毒(HBV)前C基因區(qū)1896位點(diǎn)(nt1896)的變異是較常見(jiàn)的變異,HBV變異后對(duì)乙肝診斷、治療、預(yù)防都產(chǎn)生重大影響。 目的:了解HBsAg(+)/HBeAb(+)/HBcAb(+)和HBsAg(+)/HBeAg(+) /HBcAb(+)的慢性乙肝病人血清HBV DNA前C基因區(qū)nt1896的變異情況及其與HBV DNA水平及轉(zhuǎn)氨酶(ALT)關(guān)系。 方法:將所有的實(shí)驗(yàn)對(duì)象分為HBsAg(+)/HBeAb(+)/HBcAb(+)組和HBsAg(+)/HBeAg(+)/HBcAb(+)組,分別檢測(cè)肝功能指標(biāo),進(jìn)一步根據(jù)ALT分組。用免疫熒光PCR法定量檢測(cè)HBV DNA并用聚合酶鏈反應(yīng)雜交(PCR—ELISA)檢測(cè)HBV前C區(qū)nt1896位點(diǎn)的變異情況。用χ~2檢驗(yàn)進(jìn)行統(tǒng)計(jì)學(xué)分析,P0.05被認(rèn)為有差異。 結(jié)果:172例患者中有89例HBV DNA陽(yáng)性,其中58例發(fā)生nt1896位點(diǎn)變異,變異率為65.2%(58/89)。HBsAg(+)/HBeAg(+)/HBcAb組的106例中,血清HBV DNA陽(yáng)性64例,陽(yáng)性率60.4%,平均濃度1.46×10~7(2.15×10~3—5.0×10~7)拷貝/ml , nt1896變異40例,變異率為62.5%(40/64)。HBsAg(+)/HBeAb(+)/HBcAb組的66例中, HBV DNA陽(yáng)性25例,陽(yáng)性率37.9%,平均濃度3.01×10~6(1.10×10~3—5.0×10~7)拷貝/ml。nt1896變異18例,變異率為72.0%(18/25)。經(jīng)統(tǒng)計(jì)分析,兩組HBV DNA陽(yáng)性率有顯著差異, nt1896位變異率無(wú)顯著差異。根據(jù)ALT范圍進(jìn)一步分組發(fā)現(xiàn),在HBsAg(+)/HBeAb(+)/HBcAb(+)患者中ALT升高組(40U/L)DNA(+)的15例全部發(fā)生變異,變異率100%,而ALT正常組HBV DNA(+)的10例中只有3例發(fā)生變異,變異率30%(3/10),兩組間P0.05。 結(jié)論:HBsAg(+)/HBeAg(+)/HBcAb(+)和HBsAg(+)/HBeAb(+) /HBcAb(+)慢性乙型肝炎病人都存在較高的前C區(qū)nt1896變異率( P0.05)。前C區(qū)A1896變異可能是影響HBV DNA復(fù)制的一個(gè)因素,尤其對(duì)HBsAg(+)/HBeAb(+)/HBcAb(+)的乙肝病人,前C區(qū)變異陽(yáng)性者比無(wú)前C區(qū)變異者伴有更高水平的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.
【學(xué)位授予單位】:大連醫(yī)科大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2007
【分類號(hào)】:R373

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