乙型肝炎血清标志物模式及前S1抗原与乙型肝炎病毒DNA定量检测的关系
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摘要
目的:探讨乙型肝炎病毒血清标志物(hepatitis B virus serum markers,HBV-M)及前S1抗原(preS1Ag)与HBV-DNA含量的相关性及其临床意义。方法:收集2016年12月至2018年1月于徐州医科大学附属医院就诊的556例乙型病毒肝炎患者的外周血。分别采用电化学发光法、磁微粒化学发光技术检测乙型肝炎病毒血清标志物和乙型肝炎病毒前S1抗原(HBV pre-S1Ag);运用荧光定量聚合酶链反应(fluorescence quantitative PCR,qRT-PCR)测定血清HBV-DNA含量。结果:HBV不同血清模式下,HBV-DNA与Pre-S1Ag检测结果比较差异有统计学意义(P<0.05)。乙型肝炎表面抗原(HBsAg)、乙型肝炎e抗原(HBeAg)、乙型肝炎核心抗体(抗-HBc)阳性组(1,3,5模式)HBV-DNA检出率92.70%,pre-S1Ag检出率97.08%;HBsAg,乙型肝炎e抗体(HBeAb),抗-HBc阳性组(1,4,5模式)HBV-DNA检出率54.62%,pre-S1Ag检出率86.92%;HBsAg,HBeAg,HBeAb,抗-HBc阳性组(1,3,4,5模式)HBV-DNA检出率95.83%,pre-S1Ag检出率100%;HBsAg,乙型肝炎表面抗体(HBsAb),HBeAb,抗-HBc阳性组(1,2,4,5模式)HBV-DNA检出率41.67%,pre-S1Ag检出率79.17%。HBsAb,HBeAb,抗-HBc阳性组(2,4,5模式)均未检出HBV-DNA与pre-S1Ag。HBeAg阳性患者外周血中HBV-DNA和HBV pre-S1Ag检出率依次为92.74%和94.97%。结论:HBV血清标志物检测可辅助诊断是否感染HBV。Pre-S1Ag可作为一个较好的指标来判断乙型肝炎病毒的感染、复制以及活动性状况,但尚不能取代HBV-DNA定量。HBV-DNA定量与HBV血清标志物的联合应用可提高乙型肝炎的诊断效率。
Objective: To explore the relationship between hepatitis B virus DNA(HBV-DNA) and HBV serum markers(HBV-M) as well as HBV pre-S1 Ag. Methods: In all, 556 peripheral blood samples were prospectively collected from patients who are suffering from HBV at the Affiliated Hospital of Xuzhou Medical University between December 2016 and Januar y 2018. HBV-M and pre-S1 Ag were respectively detected with electrochemiluminescence and magnetic particles chemiluminescence method. The content of HBV-DNA was analyzed by fluorescence quantitative PCR(qRT-PCR). Results: The positive rates between HBV pre-S1 Ag and HBV-DNA were significantly different among the different HBV-M mode group(P<0.05). In HBsAg, HBeAg, anti-HBc positive group(1, 3, 5 modes), the positive rate of HBV-DNA and HBV pre-S1 Ag were 92.70% and 97.08% respectively. These quantitative indicators respectively reached 54.62% and 86.92% in HBsAg, HBeAb, anti-HBc positive group(1, 4, 5 modes). In the model of HBsAg(+)/HBeAg(+)/HBeAb(+)/anti-HBc(+) group, the positive rate of HBV-DNA and HBV pre-S1 Ag were 95.83% and 100% respectively. In the model of HBsAg(+)/HBsAb/HBeAb(+)/anti-HBc(+), HBV-DNA detection rate was 41.67% and pre-S1 Ag account for 79.17%. However, HBV-DNA and HBV pre-S1 Ag were not detected in HBsAb, HBeAb, anti-HBc positive group(2, 4, 5 modes). Overall, the positive rate of HBV-DNA and HBV pre-S1 Ag were respectively 92.74% and 94.97% in patients with HBeAg(+). Conclusion: The detection of HBV serum marker can help to diagnose HBV infection. HBV pre-S1 Ag is a better index, which can determine the infection, reproduction and activity of HBV, however, it still can't substitute HBV-DNA. HBV pre-S1 Ag, a good parameter in judgment the infection, replication and activity of HBV, can't replace the HBV-DNA quantification. The combination of the HBV-DNA quantification and the HBV serum markers detection can improve the diagnostic efficiency of hepatitis B.
Objective: To explore the relationship between hepatitis B virus DNA(HBV-DNA) and HBV serum markers(HBV-M) as well as HBV pre-S1 Ag. Methods: In all, 556 peripheral blood samples were prospectively collected from patients who are suffering from HBV at the Affiliated Hospital of Xuzhou Medical University between December 2016 and Januar y 2018. HBV-M and pre-S1 Ag were respectively detected with electrochemiluminescence and magnetic particles chemiluminescence method. The content of HBV-DNA was analyzed by fluorescence quantitative PCR(qRT-PCR). Results: The positive rates between HBV pre-S1 Ag and HBV-DNA were significantly different among the different HBV-M mode group(P<0.05). In HBsAg, HBeAg, anti-HBc positive group(1, 3, 5 modes), the positive rate of HBV-DNA and HBV pre-S1 Ag were 92.70% and 97.08% respectively. These quantitative indicators respectively reached 54.62% and 86.92% in HBsAg, HBeAb, anti-HBc positive group(1, 4, 5 modes). In the model of HBsAg(+)/HBeAg(+)/HBeAb(+)/anti-HBc(+) group, the positive rate of HBV-DNA and HBV pre-S1 Ag were 95.83% and 100% respectively. In the model of HBsAg(+)/HBsAb/HBeAb(+)/anti-HBc(+), HBV-DNA detection rate was 41.67% and pre-S1 Ag account for 79.17%. However, HBV-DNA and HBV pre-S1 Ag were not detected in HBsAb, HBeAb, anti-HBc positive group(2, 4, 5 modes). Overall, the positive rate of HBV-DNA and HBV pre-S1 Ag were respectively 92.74% and 94.97% in patients with HBeAg(+). Conclusion: The detection of HBV serum marker can help to diagnose HBV infection. HBV pre-S1 Ag is a better index, which can determine the infection, reproduction and activity of HBV, however, it still can't substitute HBV-DNA. HBV pre-S1 Ag, a good parameter in judgment the infection, replication and activity of HBV, can't replace the HBV-DNA quantification. The combination of the HBV-DNA quantification and the HBV serum markers detection can improve the diagnostic efficiency of hepatitis B.
引文
1.庄辉.乙型肝炎流行病学研究进展[J].中国医学前沿杂志(电子版), 2009, 1(2):18-24.ZHUANG Hui. Advances in epidemiology of hepatitis B[J]. Chinese Journal of the Frontiers of Medical Science. Electronic Version, 2009,1(2):18-24.
2 .杨沛华.非免疫清除期乙型肝炎患者行肾结石手术后HBVLP、HBV-M及HBV-DNA变化研究[C].江西省第四次中西医结合肝病学术研讨会暨全国中西医结合肝病新进展学习班论文汇编, 2014.YANG Peihua. Study on the changes of HBV-LP, HBV-M and HBVDNAafterrenalcalculusoperationinpatientswithnon-immune clearance of hepatitis B[C]. The Fourth Academic Symposium on Liver Disease Combined with Chinese and Western Medicine in Jiangxi and a Compilation of New Progress of Chinese and Western Medicine on Liver Disease, 2014.
3 .陈仁,廖金瑶,罗晓丹,等.慢性乙型肝炎患者HBsAg水平与HBVDNA相关性研究[J].中华疾病控制杂志, 2016, 20(8):856-859.CHENRen,LIAOJinyao,LUOXiaodan,etal.Studyonthe relationship of the HBsAg levels and HBV-DNA in the chronic hepatitis B patients[J]. Chinese Journal of Disease Control and Prevention,2016, 20(8):856-859.
4 .吴小飞,蒋道荣,姚登福,等.乙型肝炎病毒感染者血清HBVDNA载量测定的临床意义[J].中国交通医学杂志, 2005, 19(3):218-220.WU Xiaofei, JIANG Daoyong, YAO Dengfu, et al. Clinical significance ofquantitativedeterminationofserumHBV-DNAinpatients withhepatitisBvirusinfection[J].ChineseMedicalJOurnalof Communications, 2005, 19(3):218-220.
5 .中华医学会肝病学分会.慢性乙型肝炎防治指南(2015更新版)[J].肝脏, 2015, 33(12):321-340.Liver Disease Branch of Chinese Medical Association. Guidelines for the prevention and treatment of chronic hepatitis B(2015 update)[J].Chinese Hepatology, 2015, 33(12):321-340.
6 .朱珉之,杭双熊,申红玉.乙型肝炎病毒携带产妇血清标志物模式与血清及乳汁HBV-DNA相关性研究[J].海南医学, 2014,25(13):1958-1960.ZHU Minzhi, HANG Shuangxiong, SHEN Hongyu. Study on the hepatitis B serum markers and the correlation between serum and milk HBV-DNA in HBV-infectious pregnant women[J]. Hainan Medical Journal, 2014, 25(13):1958-1960.
7 .韩峰,郑正茂.乙型肝炎血清标志物联合HBV-DNA检测在HBV感染诊断中的应用研究[J].当代医学, 2017, 23(34):56-57.HAN Feng, ZHENG Zhengmao. Application of hepatitis B serum markers combined with HBV-DNA in diagnosis of HBV infection[J].Contemporary Medicine, 2017, 23(34):56-57.
8 .Bruss V, Gerlich WH. Formation of transmembraneous hepatitis B e-antigen by cotranslational in vitro processing of the viral precore protein[J]. Virology, 1988, 163(2):268-275.
9 .方有兵,沈际佳,陆应玉,等.乙型肝炎病毒前S1抗原的临床应用评价[J].安徽医学, 2006, 27(3):201-202.FANG Youbing, SHEN Jijia, LU Yingyu, et al. Clinical evaluation with pre-S1 antigen of hepatitis B virus[J]. Anhui Medical Journal, 2006, 27(3):201-202.
10 .侯晓菁,梁艳,何凤春,等.乙型肝炎病毒前S1抗原与e抗原、乙型肝炎病毒DNA的相关性分析[J].第二军医大学学报, 2007,28(12):1306-1308.HOU Xiaojing, LIANG Yan, HE Fengchun, et al. Correlation analysis betweenHBVpre-S1antigenwithHBeAgandHBVDNA[J].Academic Journal of Second Military Medical Universit, 2007, 28(12):1306-1308.
11 .邓乐,温志立,何金秋,等.乙型肝炎患者联合检测血清前S1、前S2抗原、E抗原的临床意义[J].中华临床医师杂志(电子版),2012, 6(1):147-150.DENG Le, WEN Zhili, HE Jinqiu, et al. The clinical significance of combined detection of serum pre S1, pre S2 antigen and E antigen by hepatitis B patients[J]. Chinese Journal of Clinicians. Electronic Version, 2012, 6(1):147-150.
12 .Lee SA, Kim KJ, Kim DW, et al. Male-specific W4P/R mutation in the pre-S1 region of hepatitis B virus, increasing the risk of progression of liver diseases in chronic patients[J]. J Clin Microbiol, 2013, 51(12):3928-3936.
13 .王菲,许爱玲,辛霞霞,等.乙型肝炎患者血清HBeAg和抗-HBe与HBV DNA定量的关系[J].临床肝胆病杂志, 2015, 31(4):534-536.WANGFei,XUAiling,XINXiaxia,etal.Relationshipbetweena system of hepatitis B and HBV DNA quantification[J]. Chinese Journal of Clinical Hepatology, 2015, 31(4):534-536.
14 .王凤敏,李志.乙型肝炎不同血清模式及乙型肝炎DNA定量与前S1抗原联合检测的临床意义[J].国际病毒学杂志, 2016,23(2):105-107.WANGFengmin,LIZhi.Clinicalvaluesofcombinedanalysison serological patterns, virus DNA liter and pre-S1 antigen for hepatitis B[J]. International Journal of Virology, 2016, 23(2):105-107.
15 .王斌,彭静.乙型肝炎病毒Pre-S1 Ag作为病毒复制指标的临床价值[J].中国保健营养, 2017, 27(25):72-73.WANG Bin, PENG Jing. The clinical value of Pre-S1 Ag as hepatitis B virus[J]. China Health Care&Nutrition, 2017, 27(25):72-73.
2 .杨沛华.非免疫清除期乙型肝炎患者行肾结石手术后HBVLP、HBV-M及HBV-DNA变化研究[C].江西省第四次中西医结合肝病学术研讨会暨全国中西医结合肝病新进展学习班论文汇编, 2014.YANG Peihua. Study on the changes of HBV-LP, HBV-M and HBVDNAafterrenalcalculusoperationinpatientswithnon-immune clearance of hepatitis B[C]. The Fourth Academic Symposium on Liver Disease Combined with Chinese and Western Medicine in Jiangxi and a Compilation of New Progress of Chinese and Western Medicine on Liver Disease, 2014.
3 .陈仁,廖金瑶,罗晓丹,等.慢性乙型肝炎患者HBsAg水平与HBVDNA相关性研究[J].中华疾病控制杂志, 2016, 20(8):856-859.CHENRen,LIAOJinyao,LUOXiaodan,etal.Studyonthe relationship of the HBsAg levels and HBV-DNA in the chronic hepatitis B patients[J]. Chinese Journal of Disease Control and Prevention,2016, 20(8):856-859.
4 .吴小飞,蒋道荣,姚登福,等.乙型肝炎病毒感染者血清HBVDNA载量测定的临床意义[J].中国交通医学杂志, 2005, 19(3):218-220.WU Xiaofei, JIANG Daoyong, YAO Dengfu, et al. Clinical significance ofquantitativedeterminationofserumHBV-DNAinpatients withhepatitisBvirusinfection[J].ChineseMedicalJOurnalof Communications, 2005, 19(3):218-220.
5 .中华医学会肝病学分会.慢性乙型肝炎防治指南(2015更新版)[J].肝脏, 2015, 33(12):321-340.Liver Disease Branch of Chinese Medical Association. Guidelines for the prevention and treatment of chronic hepatitis B(2015 update)[J].Chinese Hepatology, 2015, 33(12):321-340.
6 .朱珉之,杭双熊,申红玉.乙型肝炎病毒携带产妇血清标志物模式与血清及乳汁HBV-DNA相关性研究[J].海南医学, 2014,25(13):1958-1960.ZHU Minzhi, HANG Shuangxiong, SHEN Hongyu. Study on the hepatitis B serum markers and the correlation between serum and milk HBV-DNA in HBV-infectious pregnant women[J]. Hainan Medical Journal, 2014, 25(13):1958-1960.
7 .韩峰,郑正茂.乙型肝炎血清标志物联合HBV-DNA检测在HBV感染诊断中的应用研究[J].当代医学, 2017, 23(34):56-57.HAN Feng, ZHENG Zhengmao. Application of hepatitis B serum markers combined with HBV-DNA in diagnosis of HBV infection[J].Contemporary Medicine, 2017, 23(34):56-57.
8 .Bruss V, Gerlich WH. Formation of transmembraneous hepatitis B e-antigen by cotranslational in vitro processing of the viral precore protein[J]. Virology, 1988, 163(2):268-275.
9 .方有兵,沈际佳,陆应玉,等.乙型肝炎病毒前S1抗原的临床应用评价[J].安徽医学, 2006, 27(3):201-202.FANG Youbing, SHEN Jijia, LU Yingyu, et al. Clinical evaluation with pre-S1 antigen of hepatitis B virus[J]. Anhui Medical Journal, 2006, 27(3):201-202.
10 .侯晓菁,梁艳,何凤春,等.乙型肝炎病毒前S1抗原与e抗原、乙型肝炎病毒DNA的相关性分析[J].第二军医大学学报, 2007,28(12):1306-1308.HOU Xiaojing, LIANG Yan, HE Fengchun, et al. Correlation analysis betweenHBVpre-S1antigenwithHBeAgandHBVDNA[J].Academic Journal of Second Military Medical Universit, 2007, 28(12):1306-1308.
11 .邓乐,温志立,何金秋,等.乙型肝炎患者联合检测血清前S1、前S2抗原、E抗原的临床意义[J].中华临床医师杂志(电子版),2012, 6(1):147-150.DENG Le, WEN Zhili, HE Jinqiu, et al. The clinical significance of combined detection of serum pre S1, pre S2 antigen and E antigen by hepatitis B patients[J]. Chinese Journal of Clinicians. Electronic Version, 2012, 6(1):147-150.
12 .Lee SA, Kim KJ, Kim DW, et al. Male-specific W4P/R mutation in the pre-S1 region of hepatitis B virus, increasing the risk of progression of liver diseases in chronic patients[J]. J Clin Microbiol, 2013, 51(12):3928-3936.
13 .王菲,许爱玲,辛霞霞,等.乙型肝炎患者血清HBeAg和抗-HBe与HBV DNA定量的关系[J].临床肝胆病杂志, 2015, 31(4):534-536.WANGFei,XUAiling,XINXiaxia,etal.Relationshipbetweena system of hepatitis B and HBV DNA quantification[J]. Chinese Journal of Clinical Hepatology, 2015, 31(4):534-536.
14 .王凤敏,李志.乙型肝炎不同血清模式及乙型肝炎DNA定量与前S1抗原联合检测的临床意义[J].国际病毒学杂志, 2016,23(2):105-107.WANGFengmin,LIZhi.Clinicalvaluesofcombinedanalysison serological patterns, virus DNA liter and pre-S1 antigen for hepatitis B[J]. International Journal of Virology, 2016, 23(2):105-107.
15 .王斌,彭静.乙型肝炎病毒Pre-S1 Ag作为病毒复制指标的临床价值[J].中国保健营养, 2017, 27(25):72-73.WANG Bin, PENG Jing. The clinical value of Pre-S1 Ag as hepatitis B virus[J]. China Health Care&Nutrition, 2017, 27(25):72-73.