自然變異與干擾素誘導(dǎo)變異中HBV突變位點(diǎn)的規(guī)律及HBV突變與抗病毒藥物關(guān)系研究
發(fā)布時間：2019-01-01 21:52
【摘要】：目的 比較HBV-BCP區(qū)/前C/C區(qū)自然變異者與干擾素誘導(dǎo)變異者變異位點(diǎn)的規(guī)律，進(jìn)而初步分析是否存在特定的干擾素誘導(dǎo)突變位點(diǎn)；探討普通干擾素和拉米夫定在HBV-BCP區(qū)/前C/C區(qū)自然突變者中的短期抗病毒療效；探討普通干擾素誘導(dǎo)的HBV-BCP區(qū)/前C/C區(qū)突變者序貫應(yīng)用聚乙二醇干擾素和拉米夫定序貫抗病毒治療的短期療效。 方法 采用回顧性隊(duì)列研究，病例來自于鄭州大學(xué)第一附屬醫(yī)院感染科門診的104例檢測出HBV-C基因區(qū)段（C基因啟動子（BCP）/前C/C基因）突變的HBeAg陰性的慢性乙型肝炎（CHB-e）患者，據(jù)突變前有無干擾素治療史分為自然變異組(A組，60例)和干擾素誘導(dǎo)變異組（B組，44例），通過分析兩組突變位點(diǎn)的規(guī)律，進(jìn)一步確定HBV-C基因區(qū)段是否存在干擾素誘導(dǎo)的特點(diǎn)突變位點(diǎn)；A組根據(jù)抗病毒藥物的選擇分為普通干擾素組（A1組，32例）和拉米夫定組（A2組，28例），檢測兩組抗病毒治療6個月后的ALT、HBV-DNA水平；B組停用普通干擾素，根據(jù)其再次抗病毒藥物的選擇分為聚乙二醇干擾素組（B1組，共16例）和拉米夫定組（B2組，共28例），檢測兩組抗病毒治療6個月后的ALT、HBV-DNA水平。 結(jié)果 1．60例HBV自然變異者（A組）與44例干擾素誘導(dǎo)變異者（B組）相比，前C區(qū)G1896A位點(diǎn)在兩組的突變率分別為73.33%和68.18%，兩組差異無統(tǒng)計(jì)學(xué)意義（P0.05）；BCP區(qū)雙位點(diǎn)（A1762T并G1764A）在兩組的突變率分別為71.67%和65.90%，兩組差異無統(tǒng)計(jì)學(xué)意義（P0.05）；C基因區(qū)熱點(diǎn)突變位點(diǎn)（I97L、S87G、L60V）的突變率在B組明顯高于A組，差異有統(tǒng)計(jì)學(xué)意義（P0.05）。 2．A組60例自然變異者中32例（A1組）和28例（A2組）分別接受普通干擾素和拉米夫定抗病毒治療6個月后，ALT復(fù)常率分別為90.63%和93.75%，兩組差異無統(tǒng)計(jì)學(xué)意義（P0.05）；HBV-DNA陰轉(zhuǎn)率分別為96.43%和100%，且差異無統(tǒng)計(jì)學(xué)意義（P0.05）。 3．B組44例普通干擾素誘導(dǎo)變異者均停用普通干擾素干擾素，其中B1組（16例）和B2組（28例）分別接受聚乙二醇干擾素和拉米夫定序貫抗病毒治療6個月后，兩組ALT復(fù)常率分別為31.25%和75.00%，，B2組明顯高于B1組且差異有統(tǒng)計(jì)學(xué)意義（P＜0.05）；兩組HBV-DNA陰轉(zhuǎn)率分別為37.50%和82.14%，B2組明顯高于B1組且差異有統(tǒng)計(jì)學(xué)意義。 結(jié)論 1．HBV-BCP區(qū)/前C/C區(qū)自然變異者與干擾素誘導(dǎo)變異者前C區(qū)G1896A位點(diǎn)及BCP區(qū)A1762T并G1764A雙位點(diǎn)均有較高的突變率，但兩組無明顯差異，C基因區(qū)熱點(diǎn)突變位點(diǎn)（I97L、S87G、L60V）在干擾素誘導(dǎo)突變組明顯高于自然變異組，我們推測C基因區(qū)熱點(diǎn)突變位點(diǎn)（I97L、S87G、L60V）可能是干擾素持續(xù)作用后的特定突變位點(diǎn)。 2．HBV-BCP區(qū)/前C/C區(qū)自然變異者，干擾素和拉米夫定的近期應(yīng)答率均較高且無明顯差異。 3．普通干擾素誘導(dǎo)HBV-BCP區(qū)/前C/C區(qū)變異者,應(yīng)用拉米夫定序貫抗病毒治療較聚乙二醇干擾素效果好。
[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.
【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R512.62
本文編號：2398144
[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.
【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R512.62
【參考文獻(xiàn)】
相關(guān)期刊論文 前9條
1 邱望龍,李福元,管岑,潘志靈,黃四邑;慢性乙型肝炎C基因啟動子變異與干擾素治療應(yīng)答的關(guān)系[J];實(shí)用肝臟病雜志;1998年03期
2 朱銀芳;顧錫炳;蔣亦明;吳杭源;;HBeAg陰性的慢性乙型病毒性肝炎外周血T細(xì)胞亞群的變化[J];現(xiàn)代中西醫(yī)結(jié)合雜志;2011年21期
3 徐丙發(fā);范清林;魏偉;宋禮華;;干擾素-α及長效干擾素抗肝炎病毒作用機(jī)制的研究進(jìn)展[J];中國藥理學(xué)通報(bào);2008年10期
4 郎振為,韓紅蕾,許德軍,徐瑞平,呂運(yùn)海;干擾素治療前后慢性乙型肝炎患者的血清學(xué)和組織學(xué)觀察[J];中華傳染病雜志;2002年02期
5 王永福,耿立霞,郭春林,楊國安,陳鵬,王宏坤;乙型肝炎病毒前C區(qū)變異對干擾素療效的影響[J];中國煤炭工業(yè)醫(yī)學(xué)雜志;2003年12期
6 韓永年,張欣欣,陸志檬;乙型肝炎病毒變異與干擾素治療的關(guān)系[J];肝臟;1999年03期
7 萬學(xué)發(fā),鄭松柏,肖宏,蔡楓,徐偉民;外周血T細(xì)胞亞群及有關(guān)細(xì)胞因子水平與前C區(qū)變異相關(guān)性研究[J];肝臟;2003年04期
8 ;In vitro resistance to interferon of hepatitis B virus with precore mutation[J];World Journal of Gastroenterology;2005年05期
9 Yoshihiro Furuichi;Hirotake Tokuyama;Satoshi Ueha;Makoto Kurachi;Fuminori Moriyasu;Kazuhiro Kakimi;;Depletion of CD25~+CD4~+T cells (Tregs) enhances the HBV-specific CD8~+ T cell response primed by DNA immunization[J];World Journal of Gastroenterology;2005年24期
本文編號：2398144
本文鏈接：http://www.lk138.cn/yixuelunwen/xiaohjib/2398144.html
最近更新
教材專著
