Detection of hepatitis C virus infection
-
摘要:
丙型肝炎病毒(HCV)感染的检测包括血清学检测和核酸检测(NAT),前者包括HCV抗体(抗-HCV)、核心抗原检测,后者包括定性/定量RNA检测和基因型/亚型检测。抗-HCV检测是应用最广的HCV感染筛查试验,操作简便、耗时短、成本低,但其缺点是窗口期较长,不能判别是活动性感染还是病毒已被清除,不适用于免疫缺陷人群。HCV RNA是病毒感染的直接证据,既往定性RNA检测灵敏度较高,但随着实时定量PCR技术的成熟,定量检测灵敏度不断提高,线性范围不断拓宽,适用于临床抗病毒治疗应答的监测,也正逐步取代定性检测用于血液制品的筛查。近年HCV抗原检测和抗原抗体联合检测试剂盒已用于HCV感染的筛查及治疗监测,但其灵敏度尚不及NAT。目前主流的HCV基因分型试剂检测基因型有较高的符合率,而检测亚型的结果存在较大差异,需要方法学上的改进。
Abstract:Diagnosis and treatment of hepatitis C virus (HCV) infection relies heavily on laboratory assays such as serological tests, which include the detection of anti-HCV antibody and core antigen, and nucleic acid tests (NAT) , which include the detection of qualitative/quantitative HCV RNA and genotypes/subgenotypes.Anti-HCV testing is simple, rapid and cheap for the screening of HCV infection.But it has a longer window period and not applicable in the immunosuppressed population.NAT provides direct evidence for the presence of HCV.Qualitative HCV RNA test has been used for blood screening due to its high sensitivity.Meanwhile quantitative HCV RNA testing has been widely used to monitor the antiviral response to treatment.With the development of real-time quantitative PCR the qualitative RNA assays are being replaced by the quantitative ones.Recently HCV core antigen assay and the combination antigen-antibody assay have been introduced for the early diagnosis of HCV, whereas they still remain less sensitive than NAT.Assays for the determination of HCV genotype based on sequencing, reverse hybridization or real-time PCR are highly consistent in determining genotypes.Whereas they are not very consistent in determining subtypes and need to be improved.
-
Key words:
- hepacivirus /
- hepatitis C
-
[1]Lauer GM, Walker BD.Hepatitis C virus infection[J].NEngl J Med, 2001, 345 (1) :41-52. [2] 戴志澄, 齐国明.中国病毒性肝炎:血清流行病学调查 (上卷) [M].北京:科学技术文献出版社, 1997:60-71. [3]Choo QL, Kuo G, Weiner AJ, et al.Isolation of a cDNA clone derived from a blood-borne non-A, non-B viralhepatitis genome[J].Science, 1989, 244 (4902) :359-362. [4]Alter HJ, Houghton M.Clinical Medical Research Award.Hepatitis C virus and eliminating post-transfusionhepatitis[J].Nat Med, 2000, 6 (10) :1082-1086. [5]Barrera JM, Francis B, Ercilla G, et al.Improved detectionof anti-HCV in post-transfusion hepatitis by a third-generation ELISA[J].Vox Sang, 1995, 68 (1) :15-18. [6]Centers for Disease Control and Prevention.Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronicdisease[J].MMWR Recomm Rep, 1998, 47 (RR-99) :1-39. [7]Alter MJ, Kuhnert WL, Finelli L, et al.Guidelines for laboratory testing and result reporting of antibodyto hepatitis C virus[J].MMWR Recomm Rep, 2003, 52 (RR-3) :1-16. [8]Ren FR, Lv QS, Zhuang H, et al.Significance of thesignal-to-cutoff ratios of anti-hepatitis C virus enzymeimmunoassays in screening of Chinese blood donors[J].Transfusion, 2005, 45 (11) :1816-1822. [9]魏来.亚太地区丙型肝炎病毒感染的诊断、处理和治疗共识[J].临床肝胆病杂志, 2007, 23 (5) :323-327. [10]Toyoda H, Kumada T, Kiriyama S, et al.Changes inhepatitis C virus (HCV) antibody status in patients withchronic hepatitis C after eradication of HCV infection byinterferon therapy[J].Clin Infect Dis, 2005, 40 (6) :e49-54. [11]Lefrère JJ, Girot R, Lefrère F, et al.Complete or partialseroreversion in immunocompetent individuals after self-limited HCV infection:consequences for transfusion[J].Transfusion, 2004, 44 (3) :343-348. [12]Busch MP, Glynn SA, Stramer SL, et al.A new strategy for estimating risks of transfusion-transmitted viralinfections based on rates of detection of recently infecteddonors[J].Transfusion, 2005, 45 (2) :254-264. [13]Eiras A, Sauleda S, Planelles D, et al.HCV screeningin blood donations using RT-PCR in mini-pool:theexperience in Spain after routine use for 2 years[J].Transfusion, 2003, 43 (6) :713-720. [14]NIH Consensus Statement on Management of Hepatitis C:2002 NIH Consens State Sci Statements[J].NIH ConsensState Sci Statements, 2002, 19 (3) :1-46. [15]Ghany MG, Strader DB, Thomas DL, et al.Diagnosis, management, and treatment of hepatitis C:an update[J].Hepatology, 2009, 49 (4) :1335-1374. [16]Trimoulet P, Halfon P, Pohier E, et al.Evaluation of theVERSANT HCV RNA 3.0 assay for quantification ofhepatitis C virus RNA in serum[J].J Clin Microbiol, 2002, 40 (6) :2031-2036. [17]Sarrazin C, Shiffman ML, Hadziyannis SJ, et al.Definitionof rapid virologic response with a highly sensitive real-time PCR-based HCV RNA assay in peginterferon alfa-2a plus ribavirin response-guided therapy[J].J Hepatol, 2010, 52 (6) :832-838. [18]Pawlotsky JM.More sensitive hepatitis C virus RNAdetection:what for?[J].J Hepatol, 2010, 52 (6) :783-785. [19]Chevaliez S, Bouvier-Alias M, Castéra L, et al.TheCobas AmpliPrep-Cobas TaqMan real-time polymerasechain reaction assay fails to detect hepatitis C virusRNA in highly viremic genotype 4 clinical samples[J].Hepatology, 2009, 49 (4) :1397-1398. [20]Chevaliez S, Bouvier-Alias M, Brillet R, et al.Ove-restimation and underestimation of hepatitis C virusRNA levels in a widely used real-time polymerase chainreaction-based method[J].Hepatology, 2007, 46 (1) :22-31. [21]CouroucéAM, Le Marrec N, Bouchardeau F, et al.Efficacy of HCV core antigen detection during thepreseroconversion period[J].Transfusion, 2000, 40 (10) :1198-1202. [22]Medhi S, Potukuchi SK, Polipalli SK, et al.Diagnosticutility of hepatitis C virus core antigen in hemodialysispatients[J].Clin Biochem, 2008, 41 (7-8) :447-452. [23]Sasase N, Kim SR, Kim KI, et al.Usefulness of a newimmunoradiometric assay of HCV core antigen to predictvirological response during PEG-IFN/RBV combinationtherapy for chronic hepatitis with high viral load of serumHCV RNA genotype 1b[J].Intervirology, 2008, 51 (Suppl1) :70-75. [24]Lunel F, Veillon P, Fouchard-Hubert I, et al.Antiviraleffect of ribavirin in early non-responders to interferonmonotherapy assessed by kinetics of hepatitis C virusRNA and hepatitis C virus core antigen[J].J Hepatol, 2003, 39 (5) :826-833. [25]Tanaka E, Ohue C, Aoyagi K, et al.Evaluation of a newenzyme immunoassay for hepatitis C virus (HCV) coreantigen with clinical sensitivity approximating that ofgenomic amplification of HCV RNA[J].Hepatology, 2000, 32 (2) :388-393. [26]Bouvier-Alias M, Patel K, Dahari H, et al.Clinical utilityof total HCV core antigen quantification:a new indirectmarker of HCV replication[J].Hepatology, 2002, 36 (1) :211-218. [27]Morota K, Fujinami R, Kinukawa H, et al.A new sensitiveand automated chemiluminescent microparticleimmunoassay for quantitative determination of hepatitisC virus core antigen[J].J Virol Methods, 2009, 157 (1) :8-14. [28]Park Y, Lee JH, Kim BS, et al.New automated hepatitis Cvirus (HCV) core antigen assay as an alternative to real-time PCR for HCV RNA quantification[J].J Clin Microbiol, 2010, 48 (6) :2253-2256. [29]Tuke PW, Grant PR, Waite J, et al.Hepatitis C viruswindow-phase infections:closing the window onhepatitis C virus[J].Transfusion, 2008, 48 (4) :594-600. [30]Simmonds P, Holmes EC, Cha TA, et al.Classification ofhepatitis C virus into six major genotypes and a series ofsubtypes by phylogenetic analysis of the NS-5 region[J].J Gen Virol, 1993, 74 (Pt11) :2391-2399. [31]Simmonds P, Bukh J, Combet C, et al.Consensusproposals for a unified system of nomenclature ofhepatitis C virus genotypes[J].Hepatology, 2005, 42 (4) :962-973. [32]Argentini C, Genovese D, Dettori S, et al.HCV geneticvariability:from quasispecies evolution to genotypeclassification[J].Future Microbiol, 2009, 4:359-373. [33]Lu L, Nakano T, He Y, et al.Hepatitis C virus genotypedistribution in China:predominance of closely relatedsubtype 1b isolates and existence of new genotype 6variants[J].J Med Virol, 2005, 75 (4) :538-549. [34]Hadziyannis SJ, Sette H Jr, Morgan TR, et al.Peginterferon-alpha2a and ribavirin combinationtherapy in chronic hepatitis C:a randomized study of treatment duration and ribavirin dose[J].Ann Intern Med, 2004, 140 (5) :346-355. [35]Hnatyszyn HJ.Chronic hepatitis C and genotyping:theclinical significance of determining HCV genotypes[J].Antivir Ther, 2005, 10 (1) :1-11. [36]Farnik H, Mihm U, Zeuzem S.Optimal therapy in genoty-pe 1 patients[J].Liver Int, 2009, 29 (Suppl 1) :23-30. [37]Tarantino G, CraxìA.Optimizing the treatment of chronichepatitis due to hepatitis C virus genotypes 2 and 3:areview[J].Liver Int, 2009, 29 (Suppl 1) :31-38. [38]Berg T, von Wagner M, Nasser S, et al.Extendedtreatment duration for hepatitis C virus type 1:comparing 48 versus 72 weeks of peginterferon-alfa-2a plusribavirin[J].Gastroenterology, 2006, 130 (4) :1086-1097. [39]McHutchison JG, Everson GT, Gordon SC, et al.Tela-previr with peginterferon and ribavirin for chronic HCVgenotype 1 infection[J].N Engl J Med, 2009, 360:1827-1838. [40]Kwo P, Lawitz EJ, McCone J, et al.HCV SPRINT-1 finalresults:SVR 24 from a phase 2 study of boceprevir plusPegIFN alpha-2b/ribavirin in treatment-nave subjects with genotype 1 chronic hepatitis[J].J Hepatol, 2009, 50 (Suppl 1) :S4. [41]Erhardt A, Deterding K, Benhamou Y, et al.Safety, pharmacokinetics and antiviral effect of BILB 1941, anovel hepatitis C virus RNA polymerase inhibitor, after 5days oral treatment[J].Antivir Ther, 2009, 14 (1) :23-32. [42]McCown MF, Rajyaguru S, Kular S, et al.GT-1a or GT-1b subtype-specific resistance profiles for hepatitis Cvirus inhibitors telaprevir and HCV-796[J].AntimicrobAgents Chemother, 2009, 53 (5) :2129-2132. [43]Zekri AR, El-Din HM, Bahnassy AA, et al.TRUGENEsequencing versus INNO-LiPA for sub-genotyping ofHCV genotype-4[J].J Med Virol, 2005, 75 (3) :412-420. [44]Chevaliez S, Bouvier-Alias M, Brillet R, et al.Hepatitis CVirus (HCV) genotype 1 subtype identification in new HCVdrug development and future clinical practice[J].PLoS ONE, 2009, 4 (12) :e8209.
计量
- 文章访问数: 16471
- HTML全文浏览量: 26
- PDF下载量: 2642
- 被引次数: 0