高灵敏 HBV DNA 试剂定量下限与检测下限误用可能影响慢性HBV感染的正确诊疗

摘要/Abstract

摘要： 高灵敏 HBV DNA 检测可进一步提高血浆或血清中HBV DNA检测灵敏度与定量水平,为进一步有效管理HBV感染、降低其危害提供了可能。在临床实践与相关研究中,错误或模糊应用HBV DNA 检测相关术语的现象非常普遍,其中最突出的是将HBV DNA 定量下限(LLOQ)误用为检测下限(LLOD),从而不仅明显降低HBV感染的诊断率与治疗率,影响研究结果的可靠性、准确性、一致性,也给文献学习者获取知识带来巨大障碍。本文从高灵敏检测技术特点、检测结果的报告类型及误用对临床诊治的影响等方面阐述其正确应用的注意事项及重要性。

关键词: 乙型肝炎病毒, HBV DNA, 检测下限, 定量下限

肖丽, 彭海林, 王蔚, 薛荣荣, 官正喜, 咸建春. 高灵敏 HBV DNA 试剂定量下限与检测下限误用可能影响慢性HBV感染的正确诊疗[J]. 肝脏, 2023, 28(11): 1271-1274.

参考文献

[1] 中华医学会肝病学分会,中华医学会感染病学分会. 慢性乙型肝炎防治指南(2022版)[J]. 中华肝脏病杂志, 2022, 30(12):1309-1331.
[2] 中华医学会肝病学分会. 扩大慢性乙型肝炎抗病毒治疗的专家意见[J]. 中华肝脏病杂志, 2022, 30(2):131-136.
[3] 石宇婧,丁银,敖玲,等. 极低病毒血症:抗乙型肝炎病毒治疗过程中需要关注的临床新问题[J]. 中华肝脏病杂志, 2021, 29(12):1147-1150.
[4] European Association for the Study of the Liver.?EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection[J]. J Hepatol, 2017, 67(2):370-398.
[5] Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidan[J]. Hepatology, 2018, 67(4):1560-1599.
[6] 韩宁,严丽波,唐红. 慢性乙型肝炎治疗过程中低病毒血症的临床意义和管理策略[J]. 中华肝脏病杂志, 2021, 29(12):1139-1143.
[7] Lok ASF, McMahon BJ. Chronic hepatitis B[J]. Hepatology, 2007, 45(2):507-539.
[8] 王杰,于广鑫,鲁凤民. 高灵敏度HBV DNA检测的临床应用及意义[J]. 分子诊断与治疗杂志, 2019, 11(5):343-347.
[9] 国家食品药品监督管理总局关于发布乙型肝炎病毒脱氧核糖核酸定量检测试剂注册技术审查等4项指导原则的通告(第3号)[OL]. [2023-09-25]. https://www.nmpa.gov.cn/xxgk/ggtg/ylqxggtg/ylqxqtggtg/20130517120001692.html.
[10] Clinical & Laboratory Standards Institute. EP17A2 | Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures, 2nd Edition[OL].[2023-09-25]. https://clsi.org/standards/products/method-evaluation/documents/ep17/.
[11] Ortonne V, Wlassow M, Bouvier-Alias M, et al. Diagnosis and Monitoring of Hepatitis B Virus Infection Using the Cobas? HBV Test for Use on the Cobas? 4800 System[J]. Microorganisms, 2021, 9(3).
[12] Ghosh M, Nandi S, Dutta S, et al. Detection of hepatitis B virus infection: A systematic review[J]. World J Hepatol, 2015, 7(23):2482-2491.
[13] Tian Y, Fan Z, Xu L, et al. CRISPR/Cas13a-assisted rapid and portable HBV DNA detection for low-level viremia patients[J]. Emerg Microbes Infect, 2023, 12(1):e2177088.
[14] Praveenkumar G, Nikam C, Venkata Ramana R, et al. Comparison of the Amplisure HBV Quantitative Kit with the Qiagen Artus HBV QS-RGQ Assay for Quantifying Viral DNA in Plasma Samples of Monitoring Cases[J]. Intervirology, 2021, 64(4):178-184.
[15] Tschäpe J, Cobernuss-Rahn A, Boyle S, et al. Multisite Performance Evaluation of the cobas 5800 System and Comparison to the cobas 6800/8800 Systems for Quantitative Measurement of HBV, HCV, and HIV-1 Viral Load[J]. Microbiol Spectr, 2022, 10(6):e0312522.
[16] Yan Y, Le Chang, Ji H, et al. Evaluation of the Aptima HBV Quant Assay Compared to Abbott RealTime M2000 HBV Quant Assay and Procleix Ultrio Plus dHBV Assay in Plasma Samples[J]. Microbiol Spectr, 2022, 10(4):e0176122.
[17] Cobb B, Simon C O, Stramer S L, et al. The cobas? 6800/8800 System: A new era of automation in molecular diagnostics[J]. Expert Rev Mol Diagn, 2017, 17(2):167-180.
[18] Li A Y, Liu Z, Song Y, et al. Reduction of the occurrence of occult HBV infection in infants by increasing the dose of hepatitis B vaccine: A large prospective cohort study[J]. Emerg Microbes Infect, 2020, 9(1):1881-1891.
[19] Sarin SK, Kumar M, Lau GK, et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B: A 2015 update[J]. Hepatol Int, 2016, 10(1):1-98.
[20] 鲁凤民,封波,郑素军,等. 核苷(酸)类似物经治的慢性乙型肝炎患者低病毒血症的研究现状[J]. 临床肝胆病杂志, 2021, 37(6):1268-1274.
[21] 李小鹏,李雷,袁松松,等. 高灵敏乙型肝炎病毒DNA阴性慢性乙型肝炎患者70例血清乙型肝炎病毒前基因组RNA水平的分析[J]. 中华传染病杂志, 2021, 39(9):558--561.
[22] 林燕,张月荣,王慧,等. 高灵敏HBV DNA检测和ALT对低病毒载量肝硬化患者精准抗病毒治疗的评估价值[J]. 临床肝胆病杂志, 2020, 36(11):2446-2449.
[23] 皇旭,姚磊,邓泽润,等. 481例低病毒载量HBV相关肝硬化患者临床特征分析[J]. 中华肝脏病杂志, 2021, 29(3):227-233.
[24] 胡鹏. 慢性乙型肝炎低病毒血症的研究现状和挑战[J]. 中华肝脏病杂志, 2021, 29(12):1137-1138.
[25] 邓德丽,江建宁,苏明华,等. HBeAg阴性低病毒载量慢性乙型肝炎患者的肝组织学状态与转归[J]. 中华肝脏病杂志, 2020, 28(12):1013-1017.
[26] 卢建华,杨莉,赵召霞,等. 高敏与普通荧光定量PCR技术在慢乙肝患者抗病毒疗效监测中的对比研究[J]. 分子诊断与治疗杂志, 2019, 11(5):361-364.
[27] 李静,毕燕华,黄月华,等. 高敏与普通荧光定量PCR技术在不同病毒载量慢乙肝患者HBV-DNA检测的一致性及应用价值[J]. 热带医学杂志, 2023, 23(2):198-202.
[28] Raimondo G, Locarnini S, Pollicino T, et al. Update of the statements on biology and clinical impact of occult hepatitis B virus infection[J]. J Hepatol, 2019, 71(2):397-408.
[29] 王贵强,王福生,庄辉,等. 慢性乙型肝炎防治指南(2019年版)[J]. 肝脏,2019,24(12):1335-1356.
[30] 中华医学会肝病学分会基础医学与实验诊断协作组. 乙型肝炎病毒标志物临床应用专家共识[J]. 中华肝脏病杂志, 2023, 31(4):389-400.
[31] Almeida N A A de, Paula V S de. Occult Hepatitis B virus (HBV) infection and challenges for hepatitis elimination: A literature review[J]. J Appl Microbiol, 2022, 132(3):1616-1635.
[32] Wong RJ, Kaufman HW, Niles JK, et al. Simplifying Treatment Criteria in Chronic Hepatitis B: Reducing Barriers to Elimination[J]. Clin Infect Dis, 2023, 76(3):e791-e800.
[33] Jeng WJ, Lok AS. Should Treatment Indications for Chronic Hepatitis B Be Expanded[J]?Clin Gastroenterol Hepatol, 2021, 19(10):2006-2014.
[34] McNaughton AL, Lemoine M, van Rensburg C, et al. Extending treatment eligibility for chronic hepatitis B virus infection[J]. Nat Rev Gastroenterol Hepatol, 2021, 18(3):146-147.