51 5 Vol. 51 No. 5 JOURNAL OF SHANDONG UNIVERSITY HEALTH SCIENCES 2013 5 May 2013 1671-7554 2013 05-0094 - 05 DOI 10. 6040 /j. issn. 1671-7554. 2013. 05. 021 HBV DNA 符晓莉, 王磊, 刘峰 / 250033 研究未经抗病毒治疗干预的慢性乙肝病毒 ( HBV) 感染不同阶段血清乙肝表面抗原 ( ) 定量值 的特点及其与血清 HBV DNA 水平和年龄的相关性 收集 564 例未经抗病毒治疗的慢性 HBV 感染者血 清, 分为 6 组 : 慢性 HBV 携带 65 例, 非活动性 携带 164 例,e 抗原 ( HBeAg) 阳性慢性乙型肝炎 171 例, HBeAg 阴性慢性乙型肝炎 74 例,HBeAg 阳性乙肝肝硬化 42 例,HBeAg 阴性乙肝肝硬化 48 例 采用微粒子化学 发光法检测 定量值, 荧光 PCR 定量法检测血清 HBV DNA 水平 慢性 HBV 携带 HBeAg 阳性慢性 乙型肝炎 HBeAg 阴性慢性乙型肝炎 非活动性 携带 HBeAg 阴性肝硬化和 HBeAg 阳性肝硬化 6 组的血 清 定量值依次下降, 其中位数分别为 : 4. 71( 3. 71 ~ 5. 31) 4. 04( 2. 45 ~ 5. 22) 3. 50( 2. 68 ~ 4. 43) 3. 34 ( 1. 38 ~ 4. 37) 3. 25( 1. 85 ~ 3. 88) 和 3. 15( 2. 51 ~ 3. 92) lgiu /ml,6 组间比较差异有统计学意义 ( χ 2 = 263. 0,P < 0. 001) 总慢性 HBV 感染者 ( 非活动性 携带者除外 ) 的 与 HBV DNA 呈正相关 ( r = 0. 719,P < 0. 001), 总慢性 HBV 感染者的 与年龄呈负相关 ( r = - 0. 397,P < 0. 001) 年龄均 > 40 岁的非活动性 携带与 HBeAg 阴性慢性乙型肝炎两组 定量值的差异有统计学意义 ( Z = - 3. 783,P < 0. 001), 区分 两组的 定量临界值为 3. 29 lgiu /ml 慢性 HBV 感染不同阶段的 定量值不同 ; 血清 定量值与血清 HBV DNA 水平及年龄相关 ; 定量值是预测年龄 > 40 岁的非活动性 携带是否发展为 HBeAg 阴性慢性乙型肝炎的重要指标 表面抗原定量 ; 慢性乙型肝炎 ; 乙型肝炎病毒 ; 年龄 R512. 6 A quantitative value in different stages of hepatitis B virus infection and its correlations with serum HBV DNA and age FU Xiao-li WANG Lei LIU Feng Department of Infection /Liver Diseases The Second Hospital of Shandong University Jinan 250033 China Abstract Objective To investigate the baseline quantification of different phases of hepatitis B virus infection without antiviral treatment and the relationships of with HBV DNA and age. Methods Five hundred and sixtyfour HBV-infected patients without accepting antiviral therapy were divided into 6 groups according to the phase of HBV-infection chronic HBV-carrier 65 patients inactive carrier 164 patients HBeAg-positive chronic hepatitis B 171 patients HBeAg-negative chronic hepatitis B 74 patients HBeAg-positive hepatitis B liver cirrhosis 42 patients and HBeAg-negative hepatitis B liver cirrhosis 48 patients. Serum was quantified using the Abbott ARCHITECT platform and HBV DNA by real-time fluorescence quantitative PCR method. Results The median levels in groups of chronic HBV-carrier HBeAg-positive chronic hepatitis B HBeAg-negative chronic hepatitis B inactive carrier HBeAg-negative hepatitis B liver cirrhosis and HBeAg-positive hepatitis B liver cirrhosis were 4. 71 3. 71-5. 31 4. 04 2. 45-5. 22 3. 50 2. 68-4. 43 3. 34 1. 38-4. 37 3. 25 1. 85-3. 88 and 3. 15 2013-01-07 2009ZX10002-028 E-mail wlcrb@ sdu. edu. cn
. HBV DNA 95 2. 51-3. 92 lgiu /ml respectively. Statistical difference of was found among the 6 groups χ 2 = 263. 0 P < 0. 001. quantification excepting inactive carrier was positively correlated with HBV DNA r = 0. 719 P < 0. 001. Negative correlation was found between and age r = - 0. 397 P < 0. 001. In patients older than 40 years quantification was statistically different between inactive carrier group and HBeAgnegative chronic hepatitis B group 3. 14 /3. 53 lgiu /ml P < 0. 001 and the cut-off value was 3. 29 lgiu /ml. Conclusion quantification is distributed differently in the different phases of HBV-infection. Serum is correlated with HBV DNA and age. quantitative value is an important indicator to predict whether the inactive carriers develop to the HBeAg- negative chronic hepatitis B. Key words Quantification of surface antigen Chronic hepatitis B Hepatitis B virus Age hepatitis B surface antigen PCR hepatitis B virus HBV 500 /ml 1. 3 SPSS 16. 0 1-2 HBV HBV DNA 3-4 HBV Kruskal-Wallis Mann-Whitey U Spearman HBV 0. 01 HBV DNA 2 HBV 1 1. 1 2011 6 ~ 2012 10 / 8. 93 7. 26 5. 04 ~ 8. 78 5. 68 564 HBV 3. 80 ~ 8. 00 5. 65 3. 08 ~ 8. 04 4. 74 3. 00 ~ HBV 6 7. 04 lg /ml 26 8 ~ 46 HBV 32 10 ~ 69 32 11 ~ 59 38 17 ~ 66 51 23 ~ HBeAg HBeAg 76 54 34 ~ 66 HBeAg HBeAg 2. 2 HBV HBV 2010 HBeAg HBeAg HBeAg HBeAg 5 1. 2 AR- 50 985 5 135 ~ 204 890 2 207 24 ~ 23 285 11 055 CHITECTi2000 285 ~ 167 740 3 177 475 ~ 27 095 1 428 325 ~ ARCHITECT 0. 05 8 315 1 800 70 ~ 7 545 IU /ml IU /ml 0. 05 ~ 250 IU /ml 4. 71 3. 71 ~ 5. 31 3. 34 1. 38 ~ 250 IU /ml 4. 37 4. 04 2. 45 ~ 5. 22 3. 50 2. 68 ~ 4. 43 1 500 3. 15 2. 51 ~ 3. 92 3. 25 1. 85 ~ 3. 88 lgiu /ml 6 500 HBV DNA ABI7000 2. 1 564 375 189 HBV HBeAg HBeAg HBeAg HBeAg 6 HBV DNA 7. 54 5. 66 ~ χ 2 = 263. 0 P < 0. 001
96 51 5 HBV 4 HBeAg 6 HBV 1 HBeAg 1 HBV - 11. 447 Z Mann-Whitey U HBeAg HBeAg HBeAg HBeAg - 8. 321-9. 635 HBeAg - 9. 868-1. 911 * - 6. 761 HBeAg - 8. 645-1. 498 * - 7. 363-3. 430 HBeAg - 9. 038-2. 071 * - 8. 185-4. 266-0. 210 * * P > 0. 01 2. 3 HBV DNA HBV HBV DNA r = 0. 719 P < 0. 001 HBV DNA HBeAg r = 0. 665 P < 0. 001 HBeAg r = 0. 362 P < 0. 001 HBV DNA HBV r = 0. 356 P = 0. 004 HBeAg r = 0. 654 P < 0. 001 HBeAg r = 0. 401 P < 0. 001 1 2. 4 HBV r = - 0. 397 P < 0. 001 HBeAg r = - 0. 353 r = - 0. 316 P < 0. 001 6 r = - 0. 359 P < 0. 001 5 2 2 Fig. 2 The quantitative distribution lgiu /ml in different age groups 1 Fig. 1 2. 5 HBeAg 40 117 3. 54 1. 38 ~ 4. 37 lgiu /ml HBeAg 43 3. 48 2. 72 ~ 4. 43 lgiu /ml Z = - 0. 472 P > 0. 01 > 40 47 3. 14 1. 50 ~ 4. 07 lgiu /ml HBeAg 31 HBV DNA HBeAg A 3. 53 2. 68 ~3. 91 lgiu /ml B Serum positively correlates with HBV DNA in Z = - 3. 783 P < 0. 001 HBeAg positive A and negative B chronic hepatitis B ROC 0. 754 95% CI 0. 648 ~ 0. 861
. HBV DNA 97 P <0. 001 3 3. 29 lgiu /ml 1 737. 8 IU /ml 77. 4% 63. 8% 3 > 40 HBeAg ROC Fig. 3 The ROC curve between the inactive -carrier group age > 40 and HBeAg negative chronic hepatitis B group age > 40 3 Nguyen 6 HBV HBeAg HBV r = - 0. 302 r = - 0. 418 P < 0. 001 HBV 4. 53 4. 03 HBV 3. 35 2. 86 lgiu /ml 654 HBV 7 4. 29 lgiu /ml HBV 2. 05 lgiu /ml HBV HBV Jang HBV 8 HBV HBV Child A B C DNA HBV 9 HBV DNA HBV HBeAg HBV HBV HBV DNA HBV HBV DNA HBV HBV HBV 10 HBV DNA HBeAg Chan 11 12 HBeAg HBV DNA cccdna HBV DNA HBeAg HBV DNA HBeAg HBV HBV DNA HBeAg HBV HBV DNA HBV HBV HBeAg HBV HBV DNA HBV > 40 HBV HBV HBeAg HBV 13 3. 29 lgiu /ml Kim 7 1 737. 8 IU /ml r = - 0. 451 P < 0. 001 2010 5
98 51 5 inactive chronic hepatitis B virus infection J. Clin Gastroenterol Hepatol 2012 10 3 297-302. HBeAg HBV DNA 1 3 ALT 25% 5. 2010 J. HBV DNA HBeAg 14 2011 19 1 13-24. 6 Nguyen T Thompson A J Bowden S et al. Hepatitis B HBeAg surface antigen levels during the natural history of chronic 4 508-513. HBeAg 7 Kim Y J Cho H C Choi M S et al. The change of the quantitative level during the natural course of HBV DNA chronic hepatitis B J. Liver Int 2011 31 6 817- HBeAg 823. 1 Moucari R Mackiewicz V Lada O et al. Early serum drop a strong predictor of sustained virological response to pegylated interferon alfa-2a in HBeAg-negative patients J. Hepatol 2009 49 4 1151-1157. 2 Cai W Xie Q An B et al. On-treatment serum level is predictive of sustained off-treatment virologic response to telbivudine in HBeAg positive chronic hepatitis B patients J. J Clin Virol 2010 48 1 22-26. 3 Tseng T C Liu C J Yang H C et al. Determinants of spontaneous surface antigen loss in HBeAg-negative patients with a low viral load J. Hepatol 2012 55 1 68-76. 4 Chen Y C Jeng W J Chu C M et al. Decreasing levels of predict seroclearance in patients with hepatitis B a perspective on Asia J. Hepatol 2010 52 14 8 15 8 Jang J W Yoo S H Kwon J H et al. Serum hepatitis B surface antigen levels in the natural history of chronic hepatitis B infection J. Aliment Pharmacol Ther 2011 34 HBeAg 11-12 1337-1346. 9. HBV DNA > 40 HBeAg J. 2011 19 10 743-746. ROC 1 737. 8 10 Wong D K Yuen M F Poon R T et al. Quantification IU /ml 77. 4% 63. 8% of hepatitis B virus covalently closed circular DNA in patients with hepatocellular carcinoma J. J Hepatol HBV 2006 45 4 553-559. 11 Chan H L Wong V W Wong G L et al. A longitudinal study on the natural history of serum hepatitis B sur- face antigen changes in chronic hepatitis B J. Hepatol HBV 2010 52 4 1232-1241. HBV 12 Thompson A J Nguyen T Iser D et al. Serum hepatitis B surface antigen and hepatitis B e antigen titers dis- HBV ease phase influences correlation with viral load and intrahepatic hepatitis B virus markers J. Hepatol 2010 51 6 1933-1944. 13 Jaroszewicz J Calle Serrano B Wursthorn K et al. Hepatitis B surface antigen levels in the natural history of hepatitis B virus HBV -infection a European perspective J. J Hepatol 2010 52 4 514-522. 14 Brunetto M R Oliveri F Colombatto P et al. Hepatitis B surface antigen serum levels help to distinguish active from inactive hepatitis B virus genotype D carriers J. Gastroenterology 2010 139 2 483-490. 15 Park H Lee J M Seo J H et al. Predictive values of quantification for determining the clinical course of genotype C HBeAg-negative carriers J. Liver Int 2012 32 5 796-802. ( 编辑 : 张彩凤 )