Analysis of Serum High-sensitivity HBV DNA in Patients with Chronic Hepatitis B with Low Viral Load in Kunming Area
-
摘要:
目的 探讨昆明地区持续低水平病毒血症的慢乙肝患者,高敏HBV-DNA载量、HBV的基因型分布特点、HBV P区耐药位点的突变特征,和HBeAg、HBsAg、ALT之间的关系及临床应用价值。 方法 采集2021年1月至2021年12月期间于昆明市第三人民医院就医的707例慢性乙肝患者的血清,分析高敏HBV-DNA、HBV的基因型以及HBV P区的耐药位点突变情况,并分析不同HBV-DNA载量与HBeAg、 HBsAg、ALT之间的关系。 结果 研究707例持续低载量慢性乙肝患者中,高敏HBV DNA(< 500 IU/mL)446例,占(63.50%),高敏HBV DNA 小于2000 IU/mL的慢乙肝患者共有576例,占(81.90%);HBeAg 阳性262例(37.05%);基因分型以C基因型占比最高60.53%(428/707)。在196例HBeAg阳性且HBV DNA < 2000 IU/mL患者组中,男性为主,占69.89%;ALT > 40 U/L占28.57%,有73.47%患者的HBV DNA > 20 IU/mL。在265例HBV DNA < 20 IU/mL的患者中,80.38%(213例)患者HBeAg阴性,19.62%(52例)HBeAg呈阳性。临床指标比较,HBeAg阳性率、ALT异常率、耐药位点和其它位点突变率在HBV DNA 载量水平不相同组之间差异有统计学意义(P < 0.05)。 结论 对持续低水平病毒血症的慢性乙型肝炎患者,选择高敏的PCR技术定期监测乙肝病毒HBV DNA,结合HBeAg、HBsAg 、ALT等临床指标的定量监测,可为后续患者的临床治疗提供客观的参考依据。 Abstract:Objective To investigate the relationship among high-sensitive HBV-DNA load , high-sensitivity HBV-DNA load, HBV genotype distribution, HBV P region drug resistance mutation, HBeAg, HBsAg, ALT and its value of clinical application in patients among the chronic hepatitis B with persistent low-level viremia in Kunming. Methods A total of 707 patients with chronic hepatitis B who received inpatient and outpatient treatment in the Third People’s Hospital of Kunming from January 2021 to December 2021 were selected. The relationship between different HBV-DNA loads and HBeAg, HBsAg and ALT was analyzed. Results Among the 707 chronic hepatitis B patients with persistent low load in the study, 446 cases had high-sensitivity HBV DNA load < 500 IU/ml, accounting for (63.50%), and there were 576 chronic hepatitis B patients with high-sensitivity HBV DNA < 2000 IU/ml, accounting for (81.90%); 262 cases (37.05%) were HBeAg positive; genotype C accounted for the highest proportion of 60.53% (428/707). Among the 196 chronic hepatitis B patients with HBeAg (+) and HBV DNA < 2000 IU/mL, males were dominant, accounting for 69.89%; ALT > 40 U/L accounted for 28.57% and 73.47% of patients had HBV DNA > 20 IU/mL mL. Among the 265 chronic hepatitis B patients with HBV DNA < 20 IU/mL, HBeAg (-) accounted for 80.38% (213 cases), and HBeAg (+) accounted for 19.62% (52 cases). Compared with the clinical indicators, the positive rate of HBeAg, the abnormal rate of ALT, the mutation rate of drug resistance sites and other sites were significantly different among different HBV DNA load levels (P < 0.05). Conclusion For chronic hepatitis B patients with persistent low-level viremia, the use of high sensitivity PCR technology to regularly monitor HBV DNA of hepatitis B virus in combination with quantitative monitoring of clinical indicators such as HBeAg, HBsAg, ALT, etc. can provide the objective reference for the clinical treatment of follow-up patients. -
Key words:
- Hepatitis B virus /
- Low viral load /
- High-sensitivity HBV DNA /
- Gene mutation /
- HbeAg
-
表 1 低病毒载量的慢性乙肝患者病毒学特征和基因型分布
Table 1. Virological characteristics and genotype distribution of chronic hepatitis B patients with low viral load
项目 n % 性别(男) 449 63.50 高敏HBV DNA载量(< 500 IU/mL) 446 63.08 高敏HBV DNA载量(< 2000 IU/mL) 576 81.90 HBsAg阳性 707 100.00 HBeAg阳性 262 37.05 基因型B型 278 39.32 基因型C型 428 60.53 基因型D型 1 0.10 治疗时间>1 a 707 100.00 表 2 196例HBeAg阳性且HBV DNA < 2000 IU/mL慢性乙肝患者的基本特征
Table 2. Basic characteristics of 196 chronic hepatitis B patients with HBeAg(+) and HBV DNA < 2000 IU/mL
项目 n 构成比(%) 性别 男 137 69.89(137/196) ALT(U/L) > 40 56 28.57(56/196) 高敏HBV DNA载量(IU/mL) < 20 52 26.53(52/196) 20~99 24 12.24(24/196) 100~499 54 27.55(54/196) 500~1000 38 19.39(38/196) 1000~2000 28 14.29(28/196) HBsAg(IU/mL)
(HBV DNA < 2000 IU/ mL)10~99 15 7.65(15/196) 100~999 50 25.51(50/196) 1000~9999 101 51.53(101/196) 表 3 不同HBV DNA 低载量慢性乙肝患者临床指标比较[n(%)]
Table 3. Comparison of clinical indicators in patients with chronic hepatitis B with different HBV DNA load [n(%)]
HBV DNA(IU/mL) n HBeAg(+) ALT > 40 U/L R 其它位点突变 < 20 265 52(19.62) 49(18.49) 0 0 20~99 53 24(42.28) 18(33.96) 1(1.88) 6(11.32) 100~499 128 54(42.91) 45(35.15) 6(4.69) 21(16.41) 500~1000 78 38(48.71) 21(26.92) 1(1.28) 11(14.10) 1000~2000 55 28(50.91) 16(29.09) 3(5.45) 30(54.55) >2000 128 66(51.56) 79(61.71) 2(1.56) 39(30.47) χ2 58.133 70.30 14.892 152.683 P < 0.001* < 0.001* 0.010* < 0.001* 注:R:耐药;其它位点的突变:不能确定的、证据不充分且需进一步待证实的耐药相关位点;*P < 0.05。 表 4 446例高敏 HBV DNA < 500 IU/mL 患者在不同耐药突变情况下HBV DNA水平与HBeAg、ALT异常率分析[n(%)]
Table 4. Analysis of HBV DNA level and abnormal rate of HBeAg and ALT in 446 patients with highly sensitive HBV DNA < 500 IU/mL under different drug-resistant mutations [n(%)]
HBV DNA
(IU/mL)n 耐药突变 无耐药突变 其它位点突变 ALT > 40 U/L HBeAg(+) ALT > 40 U/L HBeAg(+) ALT > 40 UL HBeAg(+) <20 265 0 0 49(18.49) 52(19.62) 0 0 20~99 53 0 1(1.89) 18(33.96) 21(39.62) 0 2(3.77) 100~499 128 2(1.56) 5(3.90) 38(29.69) 39(30.46) 5(3.90) 10(7.81) χ2 4.850 9.582 13.677 11.635 12.022 19.741 P 0.088 0.008* 0.001* 0.003* 0.002* <0.001* *P < 0.05。 -
[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]. 中国肝脏病杂志,2019,27(12):938-961. [2] Papatheodoridis G,Buti M,Cornberg M,et al. EASL clinical practice guidelines: Management of chronic hepatitis B virus infection[J]. Hepatology,2012,57(1):167-185. doi: 10.1016/j.jhep.2012.02.010 [3] Janssen,Harry,Agarwal,et al. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection European Association for the Study of the Liver[J]. Hepatology,2017,67(2):370-398. doi: 10.1016/j.jhep.2017.03.021 [4] Terrault N,Bzowej N,Chang K M,et al. AASLD guidelines for treatment of chronic hepatitis B[J]. Hepatology,2016,63(1):261-283. doi: 10.1002/hep.28156 [5] 胡鹏,任红. 2017年欧洲肝病年会乙型肝炎病毒感染临床实践指南要点[J]. 中华肝脏病杂志,2017,25(6):415-418. doi: 10.3760/cma.j.issn.1007-3418.2017.06.005 [6] 林健聪,王红翠,吴英松,等. 乙肝标志物定量测定试剂盒的性能验证及临床应用评价[J]. 分子诊断与治疗杂志,2018,10(1):47-55. doi: 10.3969/j.issn.1674-6929.2018.01.009 [7] 齐林,刘永芳. 乙型肝炎病毒DNA与血清标志物的关系[J]. 国际检验医学杂志,2017,38(1):130-131. doi: 10.3969/j.issn.1673-4130.2017.01.055 [8] 张宇,李冬,戴燕,等. 罗氏LightCyclerNano荧光定量PCR仪性能评价[J]. 检验医学与临床,2015,12(2):145-146. doi: 10.3969/j.issn.1672-9455.2015.02.001 [9] 张占卿,陆伟,翁齐铖,等. 血清病毒学标记物预测慢性乙型肝炎肝 组织病理状态的评价[J]. 同济大学学报(医学版),2015,36(4):57-63. [10] 普冬,余婷婷,王红英,等. 昆明地区乙型肝炎患者基因型和耐药情况分析[J]. 昆明医科大学学报,2019,40(11):5. [11] 张爱民, 王慧芬, 王海滨, 等. 中国30个地区HBV基因型分布特点和临床意义. 中华实验和临床病毒学杂志, 2011, 25(4): 126-128.3 [12] Lu F M,Zhuang H. Management of hepatitis B in China[J]. Chin Med J,2009,122(1):3-4. [13] Cheny M,Wus H,Qiuc N,et al. Hepatitis B virus subgenotype C2- and B2- associated mutation patterns may be responsible for liver cirrhosis and hepatocellular carcinoma,respectively[J]. Brazilian Journal of Medical and Biological Research,2013,46(7):614-622. doi: 10.1590/1414-431X20133032 [14] 楚玉兰,顾洪立,兰继,等. 慢性乙型肝炎及后期肝病患者外周血 T淋巴细胞亚群标志的研究[J]. 实用预防医学,2016,23(7):873-876. doi: 10.3969/j.issn.1006-3110.2016.07.034 [15] 卓芬,肖华,黄娟娟,等. 海南乙肝患者HBV基因型分布及临床指标的相关性[J]. 热带医学杂志,2018,18(7):720-728. [16] 中华医学会肝病学分会肝炎学组. 非一线核苷( 酸) 类似物经治慢性乙型肝炎患者治疗策略调整专家共识[J]. 中华肝脏病杂志,2019,27(5):343-346. doi: 10.3760/cma.j.issn.1007-3418.2019.05.004 [17] Kim JH,Sinn DH,Kang W,et al. Low-level viremia and the in creased risk of hepatocellular carcinoma in patients receiving entecavir treatment[J]. Hepatology,2017,66(2):335-343. doi: 10.1002/hep.28916 [18] 金速速,陈占国,余坚,等. 高敏乙型肝炎病毒脱氧核糖核酸定量检测在低病毒载量患者治疗监测中的应用[J]. 疾病监测,2018,33(1):5. [19] Sun Y,Wu X,Zhou J,et al. Persistent low level of hepatitis B virus promotes fibrosis progression during therapy[J]. Clinical Gastroenterology and Hepatology,2020,18(11):2582-2591. doi: 10.1016/j.cgh.2020.03.001 [20] 卢兆莲,陈世敏,陈英剑,等. 乙型肝炎e抗原与HBV-DNA定量及肝功能的相关性分析[J]. 河北医药,2015,37(1):92-93. [21] 闫一杰,陈新月,王晓晓,等. 48周HBsAg低水平的HBeAg阴性慢性乙型肝炎患者是获得HBsAg清除的优势人群[J]. 中华肝脏病杂志,2018,26(11):813-818. doi: 10.3760/cma.j.issn.1007-3418.2018.11.002 [22] 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,2010,52(4):1232-1241. doi: 10.1002/hep.23803 [23] 卢建华,杨莉、叶立红,等. HBsAg定量检测在慢性乙型病毒性肝炎患者诊疗中的临床意义[J]. 现代中西医结合杂志,2020,29(33):3674-3678. doi: 10.3969/j.issn.1008-8849.2020.33.007 [24] 王志刚. 肝功能指标正常慢性乙型肝炎患者丙氨酸氨基转移酶与肝细胞损害程度关系研究[J]. 中国实用医刊,2015,42(22):60-61. doi: 10.3760/cma.j.issn.1674-4756.2015.22.029 [25] Warner N,Locarnini S. The antiviral drug slceted hepatitis B virus rt Al81T/s W l72* mut ant has a domi nantnegative serretion defect and alters thetypical profile of viral rebound[J]. Hepatology,2008,48(1):88-98. doi: 10.1002/hep.22295 -