病毒活动阳性的HBeAg阴性乙肝患者免疫学标志物、病毒感染基因型以及YMDD突变分析
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摘要
目的分析病毒活动阳性的HBe Ag阴性乙肝患者免疫学标志物、病毒感染基因型以及YMDD突变,探讨HBe Ag血清学转换相关的因素。方法收集拉米夫定持续12个月治疗患者,比较病毒活动阳性HBe Ag阴性和阳性患者的病免疫标志物表达、感染病毒基因型、拉米夫定耐药的差异。结果 1HBe Ag阴性乙肝患者中病毒活动率约54.10%,明显高于HBe Ag阳性患者,差异有统计学意义(P<0.01)。2HBe Ag阳性和HBe Ag阴性患者的血清学标志物表达模式和病毒基因型分布在明显不同,差异有统计学意义(P<0.01)。3YMDD相关病毒突变体检测发现,HBe Ag阴性患者YMDD突变率达到26.6%,明显高于HBe Ag阳性患者;其中YVDD突变型在HBe Ag阴性患者中最高,差异有统计学意义(P<0.01)。结论本研究的结果提示了HBe Ag转阴对于乙肝治疗疗效判断的不准确性,其不准确性原因可能涉反应机体免疫状态的血清标志物、HBV感染的基因型以及药物相关病毒突变型别。另外,HBe Ag转阴的乙肝患者低的持续病毒应答能力在一定程度上也预示了拉米夫定治疗耐药性几率增加。
Objective To identify the correlation factors in HBeAg seroconversion by analyzing Immune serum marker,HBV gene-type,YMDD in Hepatitis b patients with Virus activity positive and serum HBeAg negative. Methods Collected the patients treated by LAM for 12 mothes and compared immune serum marker,HBV gene- type,YMDD between positive and negative HBeAg. Results 1The rate of viral activity in negative HBeAg was 54. 10% higher than positive HBeAg( P<0. 01). 2the distribution of genotypes and Immune serum marker mode was different between negative and positive HBeAg( P<0. 01). 3The rate of YMDD mutation was 26. 6% in negative HBeAg,remarkable higher than positive HBe Ag,and the type of YVDD was highest in negative HBeAg( P<0. 01). Conclusion The results suggested that HBe Ag was not accuracy for judging effect of LAM treating Hepatitis b patients,the reasons maybe include the immune serum marker,genotype of HBV infection,and YMDD mutant. In addition,HBeAg seroconversion may have potent of predicating increasing risk of resistance to lamivudine treatment.
Objective To identify the correlation factors in HBeAg seroconversion by analyzing Immune serum marker,HBV gene-type,YMDD in Hepatitis b patients with Virus activity positive and serum HBeAg negative. Methods Collected the patients treated by LAM for 12 mothes and compared immune serum marker,HBV gene- type,YMDD between positive and negative HBeAg. Results 1The rate of viral activity in negative HBeAg was 54. 10% higher than positive HBeAg( P<0. 01). 2the distribution of genotypes and Immune serum marker mode was different between negative and positive HBeAg( P<0. 01). 3The rate of YMDD mutation was 26. 6% in negative HBeAg,remarkable higher than positive HBe Ag,and the type of YVDD was highest in negative HBeAg( P<0. 01). Conclusion The results suggested that HBe Ag was not accuracy for judging effect of LAM treating Hepatitis b patients,the reasons maybe include the immune serum marker,genotype of HBV infection,and YMDD mutant. In addition,HBeAg seroconversion may have potent of predicating increasing risk of resistance to lamivudine treatment.
引文
[1]杨彦麟,肖萍,高鹏,等.HBe Ag阳性患者中乙型肝炎病毒基因型分布及YMDD变异位点分析[J].临床肝胆病杂志,2012,28(6):428-430.
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[5]杨创国,于乐成,陈金军,等.1686例慢性乙型肝炎中HBe Ag阴性与阳性患者临床和病毒学特点比较.中华内科杂志,2005,44(9):648-651.
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[10]Machado MV,Oliveira AG,Cortez-Pinto H.Hepatic steatosis in hepatitis B virus infected patients:meta-analysis of risk factors and comparison with hepatitis C infected patients[J].J Gastroenterol Hepatol,2011,26(9):1361-7.
[11]林国贤,黄庆华,郭伯棋,等.HBe Ag阳性与HBe Ag阴性慢性乙型肝炎患者的临床和病理对照[J].中国实验与临床感染病杂志,2010,4(1):27-32.
[12]王娜,张淑艳.乙型病毒性肝炎5项检测结果与HBV-DNA的关系及临床意义[J].国际检验医学杂志,2015,36(2):255-258.
[13]Juan Wang,Ling-Yao Du,Xia Zhu,et al.The predictive value of early indicators for HBe Ag seroconversion in HBe Ag-positive chronic hepatitis B patients with Telbivudine treatment for 104 weeks[J].Indian Journal of Medical Microbiology,2015,33Suppl(5):20-25.
[14]van Hemert FJ,Berkhout B,Zaaijer HL.Differential binding of tenofovir and adefovir to reverse transcriptase of hepatitis B virus[J].PLo S One,2014,9(9):e106324.
[15]González López Ledesma MM,Mojsiejczuk LN,Rodrigo B,et al.Hepatitis B Virus Genotype Distribution and Genotype-Specific BCP/preCore Substitutions in Acute and Chronic Infections in Argentina[J].PLo S One,2015,10(3):e0121436.
[16]Tan Y,Ding K,Su J,et al.The naturally occurring YMDD mutation among patients chronically infected HBV and untreated with lamivudine:a systematic review and meta-analysis[J].PLo S One,2012,7(3):e32789.
[17]Gu EL,Yu YQ,Wang JL,et al.Response-guided treatment of cirrhotic chronic hepatitis B patients:multicenter prospective study[J].World J Gastroenterol,2015,21(2):653-660.
[2]柳文菊,江培学,朱汝祥.3种检测乙型肝炎病毒YMDD变异方法的比较[J].检验医学,2012,27(7):557-560.
[3]罗燕春,郑惠兰,谢美华,等.乙肝小三阳与HBV-DNA定量结果的关系探讨[J].海峡预防医学杂志,2006,12(2):45-46.
[4]杨艳秋.366例疑似乙型肝炎患者HBV-DNA检测与乙肝五项指标结果分析[J].大理学院报,2007,6(6):276-278.
[5]杨创国,于乐成,陈金军,等.1686例慢性乙型肝炎中HBe Ag阴性与阳性患者临床和病毒学特点比较.中华内科杂志,2005,44(9):648-651.
[6]Hner Zu Siederdissen C,Cornberg M.The role of HBs Ag levels in the current management of chronic HBV infection[J].Ann Gastroenterol,2014,27(2):105-112
[7]Vlachogiannakos J,Papatheodoridis GV.HBe Ag Follow-up and indications for liver biopsy in HBe Ag-negative chronic hepatitis B virus infection with persistently normal ALT:a systematic review[J].J Hepatol,2012,57(1):196-202.
[8]Papatheodoridis GV,Manolakopoulos S,Liaw YF,et al.J Hepatol.2012Jul;57(1):196-202.ic hepatitis B:why do I treat my patients with pegylated interferon-alfa?[J].Liver Int,2014,34 Suppl 1:127-132.
[9]Papatheodoridis GV,Manolakopoulos S,Liaw YF,et al.Follow-up and indications for liver biopsy in HBe Ag-negative chronic hepatitis B virus infection with persistently normal ALT:a systematic review[J].Hepatol,2012,57(1):196-202.
[10]Machado MV,Oliveira AG,Cortez-Pinto H.Hepatic steatosis in hepatitis B virus infected patients:meta-analysis of risk factors and comparison with hepatitis C infected patients[J].J Gastroenterol Hepatol,2011,26(9):1361-7.
[11]林国贤,黄庆华,郭伯棋,等.HBe Ag阳性与HBe Ag阴性慢性乙型肝炎患者的临床和病理对照[J].中国实验与临床感染病杂志,2010,4(1):27-32.
[12]王娜,张淑艳.乙型病毒性肝炎5项检测结果与HBV-DNA的关系及临床意义[J].国际检验医学杂志,2015,36(2):255-258.
[13]Juan Wang,Ling-Yao Du,Xia Zhu,et al.The predictive value of early indicators for HBe Ag seroconversion in HBe Ag-positive chronic hepatitis B patients with Telbivudine treatment for 104 weeks[J].Indian Journal of Medical Microbiology,2015,33Suppl(5):20-25.
[14]van Hemert FJ,Berkhout B,Zaaijer HL.Differential binding of tenofovir and adefovir to reverse transcriptase of hepatitis B virus[J].PLo S One,2014,9(9):e106324.
[15]González López Ledesma MM,Mojsiejczuk LN,Rodrigo B,et al.Hepatitis B Virus Genotype Distribution and Genotype-Specific BCP/preCore Substitutions in Acute and Chronic Infections in Argentina[J].PLo S One,2015,10(3):e0121436.
[16]Tan Y,Ding K,Su J,et al.The naturally occurring YMDD mutation among patients chronically infected HBV and untreated with lamivudine:a systematic review and meta-analysis[J].PLo S One,2012,7(3):e32789.
[17]Gu EL,Yu YQ,Wang JL,et al.Response-guided treatment of cirrhotic chronic hepatitis B patients:multicenter prospective study[J].World J Gastroenterol,2015,21(2):653-660.