[1]刘　杨,彭道荣,霍　豆,等.慢性HBV 感染自然史不同阶段血清HBsAg 水平及与血清HBV-DNA 载量相关性的研究[J].现代检验医学杂志,2020,35(03):11-14.[doi:10.3969/j.issn.1671-7414.2020.03.003]
　LIU Yang,PENG Dao-rong,HUO Dou,et al.Study on Serum HBsAg Level and Its Correlation with Serum HBV-DNA Load in Different Phase of Natural History of Chronic HBV Infection[J].Journal of Modern Laboratory Medicine,2020,35(03):11-14.[doi:10.3969/j.issn.1671-7414.2020.03.003]
点击复制

慢性HBV 感染自然史不同阶段血清HBsAg 水平及与血清HBV-DNA 载量相关性的研究()
分享到：

《现代检验医学杂志》[ISSN:/CN:]

卷:
第35卷
期数:
2020年03期
页码:
11-14
栏目:
论著
出版日期:
2020-07-20

文章信息/Info

Title:
Study on Serum HBsAg Level and Its Correlation with Serum HBV-DNA Load in Different Phase of Natural History of Chronic HBV Infection
文章编号:
1671-7414（2020）03-011-04
作者:
刘　杨;  彭道荣; 霍　豆; 张　涛;  杨玉琪; 赵　媛; 秦　爽
（空军军医大学西京医院检验科，西安710032）
Author(s):
LIU Yang;  PENG Dao-rong;  HUO Dou;  ZHANG Tao;  YANG Yu-qi;  ZHAO Yuan;  QIN Shuang
（Department of Clinical Laboratory, Xijing Hospital of Air Force Medical University, Xi’an 710032, China）
关键词:
乙型肝炎病毒; 乙型肝炎病毒表面抗原; HBV DNA ; 自然史
分类号:
R512.62；Q503
DOI:
10.3969/j.issn.1671-7414.2020.03.003
摘要:
目的　研究慢性乙型肝炎病毒（hepatitis B virus ，HBV）感染自然史不同阶段血清乙型肝炎病毒表面抗原（hepatitis B virus surface antigen ，HBsAg）水平及与血清HBV-DNA 载量相关性的变化。方法　收集2018 年~ 2019 年西京医院 确诊的未经抗病毒治疗的慢性HBV 感染患者128 例，根据《慢性乙型肝炎防治指南》中HBV 感染的自然史标准划分 为四组：免疫耐受期27 例，免疫清除期30 例，低复制期48 例和再活动期23 例，采用化学发光法及荧光PCR 定量法 分别检测患者血清HBsAg 定量值和血清HBV-DNA 载量，分析不同阶段血清HBsAg 水平及与HBV-DNA 载量的相关性。 结果　不同阶段血清HBsAg 水平分别为：免疫耐受期（3.03~5.38） lg IU/ml、免疫清除期(-0.76~5.09) lg IU/ml、低 复制期（-0.88~4.27） lg IU/ml 和再活动期（-1.22~4.61）lg IU/ml，各期间差异有统计学意义（F=10.80, P <0.001）。 组间比较，免疫耐受期血清HBsAg 水平与其他三期差异均有统计学意义（t=2.757 ～ 6.092, 均P<0.01）, 免疫清除期 血清HBsAg 水平与低复制期差异有统计学意义（t=2.630, P =0.010），其余各组间血清HBsAg 水平差异无统计学意义 (P >0.05)。慢性HBV 感染自然史血清HBsAg 水平与HBV-DNA 载量总体呈正相关（r =0.517，P <0.001)，不同阶段两 者仅在低复制期无相关性（r =0.288,P =0.121），其他各期均呈正相关（r=0.467 ～ 0.672， 均P<0.05）。血清HBsAg/ HBV-DNA 比值在免疫耐受期、免疫清除期及再活动期的均值分别为0.539,0.502 及0.600，三者差异无统计学意义(P >0.05)。低复制期该比值均值为1.066，较其他三期明显升高且差异有统计学意义（t=4.223 ～ 6247，均P <0.001）。结 论　慢性HBV 感染自然史不同阶段血清HBsAg 呈动态变化，低复制期血清HBsAg 水平与HBV DNA 载量无相关性且 两者比值较其他三期明显升高，这一特征可为临床评估慢性HBV 感染者的自然病程提供更多依据。
Abstract:
To study the changes of serum Hepatitis B virus surface antigen（ HBsAg ）levels and its correlation with serum HBV-DNA in different stages of natural history chronic Hepatitis B virus （HBV ）infection. Methods　Collected 128 patients with chronic HBV infection who had not been treated with antiviral treatment at Xijing Hospital from 2018 to 2019. The patients were divided into four different infection phases according to the standard of the chronic hepatitis B prevention guideline: 28 of immune tolerant phase, 30 of immune clearance phase :30, 48 of low replicative phase, 23 of HBeAg-negative hepatitis phase. The chemiluminescence method and fluorescent PCR quantitative method were used to detect the serum HBsAg quantitative value and serum HBV-DNA load, respectively, and analyzed the serum HBsAg level and its correlation with HBVDNA load at different phases. Results　Serum HBsAg levels at different stages were respectively. immune tolerant phase （3.03-5.38） lg IU/mL, immune clearance phase(-0.76~5.09) lg IU/ml , low replicative phase（-0.88~4.27） lg IU/ml, HBeAg-negative hepatitis phase（-1.22~4.61）lg IU/ml, the HBsAg levels varied among the different phases(F=10.80,P <0.001). Comparing between groups, the HBsAg levels of the immune tolerant phase were different from other three phases (t = 2.757~ 6.092, P <0.05),and the immune clearance phase was different from the low replicative phase (t = 2.630, P <0.05). There were no differences between the other groups(P>0.05),and there was a positive correlation between serum HBsAg and HBV-DNA overall（r =0.288,P =0.121）,which was similar to the immune tolerant phase , the immune clearance phase and the HBeAg-negative hepatitis phase (r=0.467~0.672，P<0.05),no correlation was found in the low replicative phase (r=0.288, P=0.121). The ratios of HBsAg/HBV-DNA for the immune tolerant phase, the immune clearance phase and the HBeAg-negative hepatitis phase were 0.539,0.502 and 0.600 , respectively, and no significant differences were observed among them (P >0.05). The ratio was 1.066 for the low replicative phase, which was significantly higher compared with other three phases （t=4.223~6.247,P<0.001）. Conclusion　The serum HBsAg levels changed dynamically at different phases of natural history of chronic HBV infection. There was no correlation between serum HBsAg level and HBV DNA load in the low replication phase, and the ratio of HBsAg/HBV-DNA was significantly higher than the other three phases. This feature could provide more evidence for clinical evaluation of the natural course of chronic HBV infection.

参考文献/References:

[1]　 中华医学会感染病学分会，中华医学会肝病学分 会. 慢性乙型肝炎防治指南（2019 年版）[J]. 肝脏， 2019,24（12）: 1335-1356. Chinese Society of Infectious Diseases, Chinese Medical Association; Chinese Society of Hepatology, Chinese Medical Association. Guidelines for the Prevention and Treatment of Chronic Hepatitis B (2019 Edition) [J]. Chinese Hepatology, 2019, 24(12):1335-1356.
[2]　 矫淑媛, 张学平.HBsAg 定量与HBV-DNA 联合检 测在慢性乙型肝炎中的临床意义[J]. 标记免疫分析 与临床, 2015，22(12): 1245-1247,1213. JIAO Shuyuan, ZHANG Xueping. Clinical significance of combined detection of HBsAg and HBV-DNA in patients with chronic hepatitis B [J]. Labeled Immunoassay and Clinical Medicine，2015, 22(12): 1245-1247,1213.
[3]　 张金颖, 刘兰, 张永萍. 慢性乙型肝炎血清HBsAg 定量及HBsAg/HBV DNA 比值与肝组织病理炎症 活动度的相关性分析[J]. 现代中西医结合杂志， 2017，26(24): 2679-2681. 　　 ZHANG Jinying, LIU Lan, ZHANG Yongping. Correlation analysis between serum HBsAg quantification, HBsAg / HBV DNA ratio and pathological inflammatory activity of liver tissue in patients with chronic hepatitis B [J]. Modern Journal of Integrated Traditional Chinese and Western Medicine，2017，26(24): 2679- 2681.
[4]　 戴二黑, 李敏然. HBsAg 定量检测技术进展及其 临床意义[J]. 世界华人消化杂志， 2017，25(26): 2322-2328. 　　 DAI Erhei, LI Minran. HBsAg quantitafication tests:progress and clinical significance [J]. World Chinese Journal of Digestion，2017，25 (26): 2322-2328.
[5]　 朱霞, 唐红.HBsAg 定量与HBV DNA 载量在HBV 感染自然史不同阶段的临床意义[J]. 四川大学学报 ( 医学版)，2019，50(5):771-774. 　　 ZHU Xia, TANG Hong. Clinical Significance of HBsAg Quantification and HBV DNA load in different phases of natural history of HBV infection [J].Journal of Sichuan University (Medical Sciences Edition)， 2019，50 (5): 771-774.
[6]　 KARRA V K, CHOWDHURY S J, RUTTALA R, et al. Clinical significance of quantitative HBsAg titres and its correlation with HBV DNA levels in the natural history of epatitis B virus infection.[J]. Journal of Clinical and Experimental Hepatology，2016, 6(3): 209-215.
[7]　　 刘大吉. 慢性HBV 感染不同阶段血清HBsAg 定量 分析研究[D]. 兰州：兰州大学, 2017. 　　 LIU Daji. Serum HBsAg quantitative analysis in different phass of chronic HBV infection[D]. Lanzhou：Lanzhou University, 2017.
[8]　　 YAO Chih-Chien, HUNG Chao-hung, HU Tsung-Hui, et al. Incidence and predictors of HBV relapse after cessation of nucleoside analogues in HBeAg-negative patients with HBsAg ≤ 200 IU/ml.[J]. Scientific Reports，2017, 7(1):1839.
[9]　　 MARTINOT-PEIGNOUX M, CARVALHO-FILHO R, LAPALUS M, et al. Hepatitis B surface antigen serum level is associated with fibrosis severity in treatmentna?ve, e antigen-positive patients. [J]. Journal of Hepatology，2013, 58 (6): 1089-1095.
[10] 胡金燕，林坤培，周兰. 血清HBsAg，HBV DNA 水平及相关性在慢性HBV 感染过程的变化和意义 [J]. 中国医学创新，2018, 15(15): 8-11. 　　 HU Jinyan, LIN Kunpei, ZHOU Lan. Changes and significance of serum HBsAg HBV DNA levels and their correlation in chronic HBV infection [J]. Medical Innovation of China，2018，15(15): 8-11.
[11] TAN Zhaoxia, LI Maoshi, KUANG Xuemei, et al. Clinical implications of hepatitis B surface antigen quantitation in the natural history of chronic hepatitis B virus infection[J]. Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology，2014, 59(4)：228-234.
[12] CHAN H L，WONG V W，WONG G L，et al. A longitudinal study on the natural history of serum hepatitis B surface antigen changes in chronic hepatitis B [J]. Hepatology (Baltimore Md.)，2010，52(4): 1232-1241.
[13] KIMBI G C, KRAMVIS A, KEW M C . Integration of hepatitis B virus DNA into chromosomal DNA during acute hepatitis B[J].World Journal of Gastroenterology，2005, 11(41):6416-6421.
[14] 陈慎，郑水华，易素芳, 等. 乙肝肝硬化患者血清 HBsAg 与HBV-DNA 比值在不同病程差异及疗效价 值研究[J]. 现代检验医学杂志，2018, 33(4): 39-42, 46. 　　 CHEN Shen, ZHENG Shuihua, YI Sufang, et al.Difference of the ratio of HBsAg to HBV DNA in patients with different severity of chronic hepatitis B virus infection and predictive value for clinical effects[J]. Journal of Modern Laboratory Medicine, 2018, 33(4):39-42, 46.

相似文献/References:

[1]李步荣,张彤,李丽华,等.CHB患者HBV基因型及耐药突变基因联合检测临床研究[J].现代检验医学杂志,2015,30(05):40.[doi:10.3969/j.issn.1671-7414.2015.05.012]
　LI Bu-rong,ZHANG Tong,LI Li-hua,et al.Clinical Study of Combined Detection about Hepatitis B Virus Genotypes and Drug Resistant Mutation Genes in Patients with Chronic Hepatitis B[J].Journal of Modern Laboratory Medicine,2015,30(03):40.[doi:10.3969/j.issn.1671-7414.2015.05.012]
[2]景媛媛,李锦,段勇,等.青年献血人群HBV/OBI感染者血清中IL-10表达水平的分析[J].现代检验医学杂志,2015,30(05):107.[doi:10.3969/j.issn.1671-7414.2015.05.033]
　JING Yuan-yuan,LI Jin,DUAN Yong,et al.Analysis of IL-10 in Serum of Blood Donors with OBI/HBV Infection among Young Adults[J].Journal of Modern Laboratory Medicine,2015,30(03):107.[doi:10.3969/j.issn.1671-7414.2015.05.033]
[3]张鹏,施瑞洁,刘文康,等.输血前四项传染病指标检测分析研究[J].现代检验医学杂志,2015,30(05):164.[doi:10.3969/j.issn.1671-7414.2015.05.053]
　ZHANG Peng,SHI Rui-jie,LIU Wen-kang,et al.Analysis on Four Infectious Indicators before Blood Transfusion[J].Journal of Modern Laboratory Medicine,2015,30(03):164.[doi:10.3969/j.issn.1671-7414.2015.05.053]
[4]谢小娟,李小侠,李芒会,等.孕产妇及其新生儿的HBV检测结果相关性分析[J].现代检验医学杂志,2015,30(02):80.[doi:10.3969/j.issn.1671-7414.2015.02.025]
　XIE Xiao-juan,LI Xiao-xia,LI Mang-hui,et al.Correlation Analysis of Maternal and Neonatal HBV Test Results[J].Journal of Modern Laboratory Medicine,2015,30(03):80.[doi:10.3969/j.issn.1671-7414.2015.02.025]
[5]何紫琪,李从荣,尹 路.乙型肝炎病毒逆转录酶基因突变的临床意义[J].现代检验医学杂志,2016,31(04):83.[doi:10.3969/j.issn.16717-414.2016.04.022]
　HE Zi-qi,LI Cong-rong,YIN Lu.Clinical Significance of Reverse Transcriptase Gene Mutations in the Hepatitis B Virus[J].Journal of Modern Laboratory Medicine,2016,31(03):83.[doi:10.3969/j.issn.16717-414.2016.04.022]
[6]王海宁,李万顺,孙巨军.乙肝病毒血清标志物、外周血T淋巴细胞与HBV-DNA的相关性分析[J].现代检验医学杂志,2016,31(04):113.[doi:10.3969/j.issn.16717-414.2016.04.032]
　WANG Hai-ning,LI Wan-shun,SUN Ju-jun.Correlation Study on Serum Markers of Hepatitis B Virus and Peripheral T Lymphocytes as Well as HBV-DNA in Patients with Hepatitis B[J].Journal of Modern Laboratory Medicine,2016,31(03):113.[doi:10.3969/j.issn.16717-414.2016.04.032]
[7]解 娟,刘文康,李 玲,等.化学发光分析法定量检测住院患者HBV血清标志物及临床意义[J].现代检验医学杂志,2017,32(03):40.[doi:10.3969/j.issn.1671-7414.2017.03.011]
　XIE Juan,LIU Wen-kang,LI Ling,et al.Clinical Implication of HBV Serum Markers Detected with Chemiluminescent Immunoassay in Inpatients of Xi’an Area[J].Journal of Modern Laboratory Medicine,2017,32(03):40.[doi:10.3969/j.issn.1671-7414.2017.03.011]
[8]徐少华,赵 静,朱 琳,等.HBeAg阳性慢性乙型肝炎患者大量输血后其血清标志物变化研究[J].现代检验医学杂志,2017,32(06):147.[doi:10.3969/j.issn.1671-7414.2017.06.001]
　XU Shao-hua,ZHAO Jing,ZHU Lin,et al.Changes of Serum Markers in Patients with HBeAg Positive Chronic Hepatitis B after Massive Blood Transfusion[J].Journal of Modern Laboratory Medicine,2017,32(03):147.[doi:10.3969/j.issn.1671-7414.2017.06.001]
[9]张 孟a,李 倩b,周华君b,等.巢氏PCR扩增低拷贝HBV全基因组方法的建立及应用[J].现代检验医学杂志,2018,33(03):44.[doi:10.3969/j.issn.1671-7414.2018.03.013]
　ZHANG Menga,LI Qianb,ZHOU Hua-junb,et al.Establishment and Application of Nested PCR Amplification Method for the Whole Genome of HBV with the Low Copy[J].Journal of Modern Laboratory Medicine,2018,33(03):44.[doi:10.3969/j.issn.1671-7414.2018.03.013]
[10]梁湘辉,樊树洁.HBV感染者病毒载量与外周血白细胞VCS参数的相关性探讨[J].现代检验医学杂志,2018,33(06):115.[doi:10.3969/j.issn.1671-7414.2018.06.030]
　LIANG Xiang-hui,FAN Shu-jie.Correlative Study between Viral Load of Patients with HBV and VCS Parameters of Peripheral Blood Leukocytes[J].Journal of Modern Laboratory Medicine,2018,33(03):115.[doi:10.3969/j.issn.1671-7414.2018.06.030]

备注/Memo

备注/Memo:
收稿日期：2020-03-03　修回日期：2020-03-17基金项目：国家“863”计划重点项目（2011AA02A101）。 作者简介：刘杨（1988-），女，硕士，主管技师，主要从事临床免疫工作。 通讯作者：秦爽（1990-），女，学士，技师，E-mail：www.cxaq@qq.com。
更新日期/Last Update: 2020-07-20