Skip to main content
SpringerLink
Log in

Laboratory Diagnosis

  • Chapter
  • First Online:
Hepatitis C: Epidemiology, Prevention and Elimination

  • 312 Accesses

Abstract

The classic algorithm for diagnosing infection with the hepatitis C virus (HCV) requires screening of serum or plasma for HCV antibody followed by detection of HCV RNA to confirm an active infection. Assays that detect and quantify HCV core antigen provide an alternative to testing for HCV RNA. Molecular assays to quantify the HCV RNA load, determine the HCV genotype, and detect drug resistance-associated mutations are established in well-resourced practice to inform and monitor antiviral therapy, although guidance on use and interpretation continues to evolve. Hepatitis C is now curable. To reduce the large number of undiagnosed individuals and facilitate transition into care and treatment, simplified diagnostic and monitoring algorithms need to be established. Novel strategies for sampling and transport (e.g. dried blood spots) and testing (e.g. single-step molecular platforms) have been developed that can complement and potentially circumvent the requirement for sophisticated laboratory infrastructure, and a diagnosis of active infection can now be achieved at point of care using a few drops of blood collected by finger-prick. The laboratory plays a key role in supporting validation, standardisation, and implementation of the new tools and methods required to facilitate expanded access to treatment and achieve the ambitious goal of global elimination.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Feinstone SM, Kapikian AZ, Purcell RH, Alter HJ, Holland PV. Transfusion-associated hepatitis not due to viral hepatitis type A or B. N Engl J Med. 1975;292:767–70.

    Article  CAS  PubMed  Google Scholar 

  2. Houghton M. The long and winding road leading to the identification of the hepatitis C virus. J Hepatol. 2009;51:939–48.

    Article  CAS  PubMed  Google Scholar 

  3. Kuo G, Choo Q-L, Alter HJ, Gitnick GL, Redeker AG, et al. An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis. Science. 1989;244:362–4.

    Article  CAS  PubMed  Google Scholar 

  4. Kamili S, Drobeniuc J, Araujo AC, Hayden TM. Laboratory diagnostics for hepatitis C virus infection. Clin Infect Dis. 2012;55(Suppl 1):S43–8.

    Article  PubMed  Google Scholar 

  5. Reyes-Méndez MÁ, Juárez-Figueroa L, Iracheta-Hernández P, Medina-Islas Y, Ruiz-González V. Comparison of two diagnostic algorithms for the identification of patients with HCV viremia using a new HCV antigen test. Ann Hepatol. 2014;13:337–42.

    Article  PubMed  Google Scholar 

  6. Chapko MK, Dufour DR, Hatia RI, Drobeniuc J, Ward JW, Teo CG. Cost-effectiveness of strategies for testing current hepatitis C virus infection. Hepatology. 2015;62:1396–404.

    Article  PubMed  Google Scholar 

  7. Nastouli E, Thomson EC, Karayiannis P, Main J, McClure M, Muir D. Diagnosing acute hepatitis C in HIV-infected patients: nucleic acid testing compared with antibody and antigen-antibody detecting methods. J Clin Virol. 2009;44:78–80.

    Article  CAS  PubMed  Google Scholar 

  8. Baath L, Widell A, Nordenfelt E. A comparison between one first generation and three second generation anti-HCV ELISAs: an investigation in high- and low-risk subjects in correlation with recombinant immunoblot assay and polymerase chain reaction. J Virol Methods. 1992;40:287–96.

    Article  CAS  PubMed  Google Scholar 

  9. Colin C, Lanoir D, Touzet S, Meyaud-Kraemer L, Bailly F, Trepo C. Sensitivity and specificity of third-generation hepatitis C virus antibody detection assays: an analysis of the literature. J Viral Hepat. 2001;8:87–95.

    Article  CAS  PubMed  Google Scholar 

  10. Bukh J, Wantzin E, Krogsgaard K, Knudsen F, Purcell RH, Miller RH, et al. High prevalence of hepatitis C virus (HCV) RNA in dialysis patients: failure of commercially available antibody tests to identify a significant number of patients with HCV infection. J Infect Dis. 1993;168:1343–8.

    Article  CAS  PubMed  Google Scholar 

  11. Parry JV, Easterbrook P, Sands AR. One or two serological assay testing strategy for diagnosis of HBV and HCV infection? The use of predictive modelling. BMC Infect Dis. 2017;17(Suppl 1):705.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. King S, Adjei-Asante K, Appiah L, Adinku D, Beloukas A, Atkins M, et al. Antibody screening tests variably overestimate the prevalence of hepatitis C virus infection among HIV-infected adults in Ghana. J Viral Hepat. 2015;22:461–8.

    Article  CAS  PubMed  Google Scholar 

  13. Agha S, El-Mashad N, El-Malky M, et al. Prevalence of low positive anti-HCV antibodies in blood donors: schistosoma mansoni co- infection and possible role of autoantibodies. Microbiol Immunol. 2006;50:447–52.

    Article  CAS  PubMed  Google Scholar 

  14. Mullis CE, Laeyendecker O, Reynolds SJ, et al. High frequency of false-positive hepatitis C virus enzyme-linked immunosorbent assay in Rakai, Uganda. Clin Infect Dis. 2013;57:1747–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Laperche S, Nübling CM, Stramer SL, Brojer E, Grabarczyk P, Yoshizawa H, et al. Sensitivity of hepatitis C virus core antigen and antibody combination assays in a global panel of window period samples. Transfusion. 2015;55:2489–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Quinti I, Hassan N, Salman D, Shalaby H, El Zimatty D, Monier MK, Arthur RR. Hepatitis C virus-specific B cell activation: IgG and IgM detection in acute and chronic hepatitis C. J Hepatol. 1995;23:640–7.

    Article  CAS  PubMed  Google Scholar 

  17. Coppola N, Pisapia R, Tonziello G, Masiello A, Martini S, Pisaturo M, et al. Improvement in the aetiological diagnosis of acute hepatitis C: a diagnostic protocol based on the anti-HCV-IgM titre and IgG avidity index. J Clin Virol. 2009;46:222–9.

    Article  CAS  PubMed  Google Scholar 

  18. Baleriola C, Johal H, Jacka B, Chaverot S, Bowden S, Lacey S, et al. Stability of hepatitis C virus, HIV, and hepatitis B virus nucleic acids in plasma samples after long-term storage at –20 degrees C and –70 degrees C. J Clin Microbiol. 2011;49:3163–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Ticehurst JR, Hamzeh FM, Thomas DL. Factors affecting serum concentrations of hepatitis C virus (HCV) RNA in HCV genotype 1-infected patients with chronic hepatitis. J Clin Microbiol. 2007;45:2426–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. World Health Organization. Guidelines on Hepatitis B and C testing. Diagnostics for testing for hepatitis B and C infection. Geneva: WHO; 2017. p. 30–4.

    Google Scholar 

  21. Vermehren J, Kau A, Gartner BC, Gobel R, Zeuzem S, Sarrazin C. Differences between two real-time PCR-based hepatitis C virus (HCV) assays (RealTime HCV and Cobas AmpliPrep/Cobas TaqMan) and one signal amplification assay (Versant HCV RNA 3.0) for RNA detection and quantification. J Clin Microbiol. 2008;46:3880–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Chevaliez S, Bouvier-Alias M, Brillet R, Pawlotsky JM. Overestimation and underestimation of hepatitis C virus RNA levels in a widely used real-time polymerase chain reaction-based method. Hepatology. 2007;46:22–31.

    Article  CAS  PubMed  Google Scholar 

  23. Dubuisson J, Cosset FL. Virology and cell biology of the hepatitis C virus life cycle: an update. J Hepatol. 2014;61:S3–S13.

    Article  CAS  PubMed  Google Scholar 

  24. Orito E, Mizokami M, Tanaka T, Lau JY, Suzuki K, Yamauchi M, et al. Quantification of serum hepatitis C virus core protein level in patients chronically infected with different hepatitis C virus genotypes. Gut. 1996;39:876–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Chevaliez S, Soulier A, Poiteau L, Bouvier-Alias M, Pawlotsky JM. Clinical utility of hepatitis C virus core antigen quantification in patients with chronic hepatitis C. J Clin Virol. 2014;61:145–8.

    Article  CAS  PubMed  Google Scholar 

  26. Cresswell FV, Fisher M, Hughes DJ, Shaw SG, Homer G, Hassan-Ibrahim MO. Hepatitis C core antigen testing: a reliable, quick, and potentially cost-effective alternative to hepatitis C polymerase chain reaction in diagnosing acute hepatitis C virus infection. Clin Infect Dis. 2015;60:263–6.

    Article  CAS  PubMed  Google Scholar 

  27. Freiman JM, Tran TM, Schumacher SG, White LF, Ongarello S, Cohn J, Easterbrook PJ, Linas BP, Denkinger CM. Hepatitis C core antigen testing for diagnosis of hepatitis C virus infection: a systematic review and meta-analysis. Ann Intern Med. 2016;165:345–55.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Khan H, Hill A, Main J, Brown A, Cooke G. Can hepatitis C virus antigen testing replace ribonucleic acid polymerase chain reaction analysis for detecting hepatitis C virus? A systematic review. Open Forum Infect Dis. 2017;4:ofw252.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Fourati S, Feld JJ, Chevaliez S, Luhmann N. Approaches for simplified HCV diagnostic algorithms. J Int AIDS Soc. 2018;21:e25058.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Duchesne L, Njouom R, Lissock F, Tamko-Mella GF, Rallier S, Poiteau L, et al. HCV Ag quantification as a one-step procedure in diagnosing chronic hepatitis C infection in Cameroon: the ANRS 12336 study. J Int AIDS Soc. 2017;20:21446.

    Article  PubMed  PubMed Central  Google Scholar 

  31. World Health Organization. Global hepatitis report, 2017. http://www.who.int/hepatitis/publications/global-hepatitis-report2017/en/. Accessed 28 Mar 2018.

  32. Smith BD, Morgan RL, Beckett GA, Centers for Disease Control and Prevention. Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945–1965. MMWR Recomm Rep. 2012;61(RR-4):1–32.

    PubMed  Google Scholar 

  33. Yartel AK, Rein DB, Brown KA, Krauskopf K, Massoud OI, Jordan C, et al. Hepatitis C virus testing for case identification in persons born during 1945–1965: results from three randomized controlled trials. Hepatology. 2018;67:524–33.

    Article  PubMed  Google Scholar 

  34. Barocas JA, Tasillo A, Eftekhari Yazdi G, Wang J, Vellozzi C, Hariri S, et al. Population level outcomes and cost-effectiveness of expanding the recommendation for age-based hepatitis C testing in the United States. Clin Infect Dis. 2018;67:549–56.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Torian LV, Felsen UR, Xia Q, Laraque F, Rude EJ, Rose H, et al. Undiagnosed HIV and HCV infection in a New York City Emergency Department, 2015. Am J Public Health. 2018;108:652–8.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Parry S, Bundle N, Ullah S, Foster GR, Ahmad K, Tong CYW, Balasegaram S, Orkin C. Implementing routine blood-borne virus testing for HCV, HBV and HIV at a London Emergency Department—uncovering the iceberg? Epidemiol Infect. 2018;17:1–10.

    Google Scholar 

  37. Grebely J, Applegate TL, Cunningham P, Feld JJ. Hepatitis C point-of-care diagnostics: in search of a single visit diagnosis. Expert Rev Mol Diagn. 2017;17:1109–15.

    Article  CAS  PubMed  Google Scholar 

  38. Greenman J, Roberts T, Cohn J, Messac L. Dried blood spot in the genotyping, quantification and storage of HCV RNA: a systematic literature review. J Viral Hepat. 2014;22:353–61.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Lange B, Roberts T, Cohn J, Greenman J, Camp J, Ishizaki A, et al. Diagnostic accuracy of detection and quantification of HBV-DNA and HCV-RNA using dried blood spot (DBS) samples—a systematic review and meta-analysis. BMC Infect Dis. 2017;17(Suppl 1):693.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Geretti AM, King S, Adjei-Asante K, Appiah LT, Owusu DO, Sarfo FS, et al. Hepatitis C virus (HCV) RNA screening and sequencing using dry plasma spots. J Clin Virol. 2017;97:18–21.

    Article  CAS  PubMed  Google Scholar 

  41. Mohamed Z, Mbwambo J, Shimakawa Y, Poiteau L, Chevaliez S, Pawlotsky JM, et al. Clinical utility of HCV core antigen detection and quantification using serum samples and dried blood spots in people who inject drugs in Dar-es-Salaam, Tanzania. J Int AIDS Soc. 2017;20:21856.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Assoumou SA, Tasillo A, Leff JA, Schackman BR, Drainoni ML, Horsburgh CR, et al. Cost-effectiveness of one-time hepatitis C screening strategies among adolescents and young adults in primary care settings. Clin Infect Dis. 2018;66:376–84.

    Article  PubMed  Google Scholar 

  43. Barocas JA, Linas BP, Kim AY, et al. Acceptability of rapid point-of-care hepatitis C tests among people who inject drugs and utilize syringe-exchange programs. Open Forum Infect Dis. 2016;3:ofw075.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Pallarés C, Carvalho-Gomes Â, Hontangas V, Conde I, Di Maira T, Aguilera V, et al. Performance of the OraQuick Hepatitis C virus antibody test in oral fluid and fingerstick blood before and after treatment-induced viral clearance. J Clin Virol. 2018;102:77–83.

    Article  PubMed  CAS  Google Scholar 

  45. Nash M, Huddart S, Badar S, Baliga S, Saravu K, Pai M. Performance of the Xpert® HIV-1 Viral Load assay: a systematic review and meta-analysis. J Clin Microbiol. 2018;56:e01673-17.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Grebely J, Lamoury FMJ, Hajarizadeh B, Mowat Y, Marshall AD, Bajis S, et al. Evaluation of the Xpert HCV Viral Load point-of-care assay from venepuncture-collected and finger-stick capillary whole-blood samples: a cohort study. Lancet Gastroenterol Hepatol. 2017;2:514–20.

    Article  PubMed  Google Scholar 

  47. Lamoury FMJ, Bajis S, Hajarizadeh B, Marshall AD, Martinello M, et al. Evaluation of the Xpert HCV Viral Load fingerstick point-of-care assay. J Infect Dis. 2018;217:1889–96.

    Article  CAS  PubMed  Google Scholar 

  48. Llibre A, Shimakawa Y, Mottez E, Ainsworth S, Buivan TP, Firth R, et al. Development and clinical validation of the Genedrive point-of-care test for qualitative detection of hepatitis C virus. Gut. 2018;67:2017–24.

    Article  CAS  PubMed  Google Scholar 

  49. Barreiro P, Labarga P, Fernandez-Montero JV, Poveda E, de Mendoza C, Sanchez C, et al. Longitudinal changes in viral RNA concentration in patients with chronic hepatitis C and/or HIV infection in the absence of antiviral therapy. J Clin Virol. 2013;58:391–5.

    Article  CAS  PubMed  Google Scholar 

  50. Zeuzem S, Ghalib R, Reddy KR, Pockros PJ, Ben Ari Z, Zhao Y, et al. Grazoprevir-elbasvir combination therapy for treatment-naive cirrhotic and noncirrhotic patients with chronic hepatitis C virus genotype 1, 4, or 6 infection: a randomized trial. Ann Intern Med. 2015;163:1–13.

    Article  PubMed  Google Scholar 

  51. Wyles DL, Ruane PJ, Sulkowski MS, Dieterich D, Luetkemeyer A, Morgan TR, et al. Daclatasvir plus sofosbuvir for HCV in patients coinfected with HIV-1. N Engl J Med. 2015;373:714–25.

    Article  CAS  PubMed  Google Scholar 

  52. American Association for the Study of Liver Diseases and the Infectious Diseases Society of America. HCV Guidance: recommendations for testing, managing, and treating hepatitis C. 2017. https://www.hcvguidelines.org/sites/default/files/full-guidance-pdf/HCVGuidance_September_21_2017_h.pdf. Accessed 10 May 2018.

  53. European Association for the Study of the Liver. Recommendations on treatment of hepatitis C 2018. http://www.easl.eu/medias/cpg/2018/EASL%20Recommendations%20on%20Treatment%20of%20Hepatitis%20C%202018/English-report.pdf. Accessed 10 May 2018.

  54. Sidharthan S, Kohli A, Sims Z, Nelson A, Osinusi A, Masur H, Kottilil S. Utility of hepatitis C viral load monitoring on direct-acting anti-viral therapy. Clin Infect Dis. 2015;60:1743–51.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Harrington PR, Deming DJ, Komatsu TE, Naeger LK. Hepatitis C virus RNA levels during interferon-free combination direct-acting antiviral treatment in registrational trials. Clin Infect Dis. 2015;61:666–7.

    Article  PubMed  Google Scholar 

  56. Tedder RS, Tuke P, Wallis N, Wright M, Nicholson L, Grant PR. Therapy-induced clearance of HCV core antigen from plasma predicts an end of treatment viral response. J Viral Hepat. 2013;20:65–71.

    Article  CAS  PubMed  Google Scholar 

  57. Loggi E, Galli S, Vitale G, Di Donato R, Vukotic R, Grandini E, et al. Monitoring the treatment of hepatitis C with directly acting antivirals by serological and molecular methods. PLoS One. 2017;12:e0187755.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  58. European Union HCV Collaborators. Hepatitis C virus prevalence and level of intervention required to achieve the WHO targets for elimination in the European Union by 2030: a modelling study. Lancet Gastroenterol Hepatol. 2017;2:325–36.

    Article  Google Scholar 

  59. Jülicher P, Galli C. Identifying cost-effective screening algorithms for active hepatitis C virus infections in a high prevalence setting. J Med Econ. 2018;21:1–10.

    Article  PubMed  Google Scholar 

  60. Smith DB, Bukh J, Kuiken C, Muerhoff AS, Rice CM, Stapleton JT, Simmonds P. Expanded classification of hepatitis C virus into 7 genotypes and 67 subtypes: updated criteria and genotype assignment Web resource. Hepatology. 2014;59:318–27.

    Article  PubMed  Google Scholar 

  61. McNaughton AL, Sreenu VB, Wilkie G, Gunson R, Templeton K, Leitch ECM. Prevalence of mixed genotype hepatitis C virus infections in the UK as determined by genotype-specific PCR and deep sequencing. J Viral Hepat. 2018;25:524–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Pham ST, Bull RA, Bennett JM, Rawlinson WD, Dore GJ, Lloyd AR, White PA. Frequent multiple hepatitis C virus infections among injection drug users in a prison setting. Hepatology. 2010;52:1564–72.

    Article  PubMed  Google Scholar 

  63. Hézode C. Pan-genotypic treatment regimens for hepatitis C virus: advantages and disadvantages in high- and low-income regions. J Viral Hepat. 2017;24:92–101.

    Article  PubMed  Google Scholar 

  64. Verbeeck J, Stanley MJ, Shieh J, Celis L, Huyck E, Wollants E, et al. Evaluation of versant hepatitis C virus genotype assay (LiPA) 2.0. J Clin Microbiol. 2008;46:1901–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Germer JJ, Majewski DW, Rosser M, Thompson A, Mitchell PS, Smith TF, et al. Evaluation of the TRUGENE HCV 5’NC genotyping kit with the new genelibrarian module 3.1.2 for genotyping of hepatitis C virus from clinical specimens. J Clin Microbiol. 2003;41:4855–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Michelin BDA, Muller Z, Stelzl E, Marth E, Kessler HH. Evaluation of the Abbott RealTime HCV assay for quantitative detection of hepatitis C virus RNA. J Clin Virol. 2007;38:96–100.

    Article  CAS  PubMed  Google Scholar 

  67. Vermehren J, Stelzl E, Maasoumy B, Michel-Treil V, Berkowski C, Marins EG, et al. Multicenter comparison study of both analytical and clinical performance across 4 Roche HCV RNA assays utilizing different platforms. J Clin Microbiol. 2017;55:1131–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Guelfo JR, Macias J, Neukam K, Di Lello FA, Mira JA, Merchante N, et al. Reassessment of genotype 1 hepatitis C virus subtype misclassification by LiPA 2.0: implications for direct-acting antiviral treatment. J Clin Microbiol. 2014;52:4027–9.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Chueca N, Rivadulla I, Lovatti R, Reina G, Blanco A, Fernandez-Caballero JA, et al. Using NS5B sequencing for hepatitis C virus genotyping reveals discordances with commercial platforms. PLoS One. 2016;11:e0153754.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  70. Mourez T, Decroos A, Goria O, Montialoux H, De Oliveira F, Larrat S, Plantier JC, Riachi G. Misidentification of recombinant hepatitis C virus leading to treatment failure with direct acting antivirals. J Med Virol. 2018;90:994–7.

    Article  CAS  PubMed  Google Scholar 

  71. Ceccherini Silberstein F, Di Maio VC, Aragri M, Ciotti M, Cento V, Perno CF. Hepatitis C virus gene sequencing as a tool for precise genotyping in the era of new direct antiviral agents. Hepatology. 2016;63:1058–9.

    Article  PubMed  Google Scholar 

  72. Susser S, Dietz J, Schlevogt B, Zuckerman E, Barak M, Piazzolla V, et al. Origin, prevalence and response to therapy of hepatitis C virus genotype 2k/1b chimeras. J Hepatol. 2017;67:680–6.

    Article  PubMed  Google Scholar 

  73. Rodriguez C, Soulier A, Demontant V, Poiteau L, Mercier-Darty M, Bouvier-Alias M, et al. A novel standardized deep sequencing-based assay for hepatitis C virus genotype determination. Sci Rep. 2018;8:4180.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Sorbo MC, Cento V, Di Maio VC, Howe AYM, Garcia F, Perno CF, Ceccherini-Silberstein F. Hepatitis C virus drug resistance associated substitutions and their clinical relevance: update 2018. Drug Resist Updat. 2018;37:17–39.

    Article  PubMed  Google Scholar 

  75. Ribeiro RM, Li H, Wang S, Stoddard MB, Learn GH, Korber BT, et al. Quantifying the diversification of hepatitis C virus (HCV) during primary infection: estimates of the in vivo mutation rate. PLoS Pathog. 2012;8:e1002881.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Bagaglio S, Uberti-Foppa C, Morsica G. Resistance mechanisms in hepatitis C virus: implications for direct-acting antiviral use. Drugs. 2017;77:1043–55.

    Article  CAS  PubMed  Google Scholar 

  77. Jones BR, Howe AYM, Harrigan PR, Joy JB. The global origins of resistance-associated variants in the non-structural proteins 5A and 5B of the hepatitis C virus. Virus Evol. 2018;4:vex041.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Smith D, Magri A, Bonsall D, Ip CLC, Trebes A, Brown A, et al. Resistance analysis of genotype 3 hepatitis C virus indicates subtypes inherently resistant to nonstructural protein 5A inhibitors. Hepatology. 2019;69:1861–72.

    Article  CAS  PubMed  Google Scholar 

  79. Lontok E, Harrington P, Howe A, Kieffer T, Lennerstrand J, Lenz O, et al. Hepatitis C virus drug resistance-associated substitutions: state of the art summary. Hepatology. 2015;62:1623–32.

    Article  PubMed  Google Scholar 

  80. Palanisamy N, Kalaghatgi P, Akaberi D, Lundkvist Å, Chen ZW, Hu P, Lennerstrand J. Worldwide prevalence of baseline resistance-associated polymorphisms and resistance mutations in HCV against current direct-acting antivirals. Antivir Ther. 2018;23:485–93.

    Article  CAS  PubMed  Google Scholar 

  81. Dietz J, Susser S, Vermehren J, Peiffer KH, Grammatikos G, Berger A, et al. Patterns of resistance-associated substitutions in patients with chronic HCV infection following treatment with direct-acting antivirals. Gastroenterology. 2018;154:976–88.

    Article  PubMed  Google Scholar 

  82. Kan H, Imamura M, Uchida T, Hiraga N, Hayes CN, Tsuge M, et al. Protease inhibitor resistance remains even after mutant strains become undetectable by deep sequencing. J Infect Dis. 2016;214:1687–94.

    Article  CAS  PubMed  Google Scholar 

  83. Wyles DL. Resistance to DAAs: when to look and when it matters. Curr HIV/AIDS Rep. 2017;14:229–37.

    Article  PubMed  Google Scholar 

  84. Gane EJ, Metivier S, Nahass R, Ryan M, Stedman CA, Svarovskaia ES, et al. The emergence of NS5B resistance associated substitution S282T after sofosbuvir-based treatment. Hepatol Commun. 2017;1:538–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Bartlett SR, Grebely J, Eltahla AA, Reeves JD, Howe AYM, Miller V, et al. Sequencing of hepatitis C virus for detection of resistance to direct-acting antiviral therapy: a systematic review. Hepatol Commun. 2017;1:379–90.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Infection, University of Liverpool, Liverpool, UK

    Anna Maria Geretti

  2. Micropathology, Coventry, UK

    Mark Atkins

  3. Department of Clinical Virology, UCL Hospital NHS Foundation Trust, London, UK

    Eleni Nastouli

  4. Virus Reference Department, Public Health England, Colindale, UK

    Daniel Bradshaw

Authors
  1. Anna Maria Geretti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mark Atkins
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eleni Nastouli
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Daniel Bradshaw
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anna Maria Geretti .

Editor information

Editors and Affiliations

  1. Department of Hygiene, Epidemiology and Medical Statistics, National and Kapodistrian University of Athens Medical School, Athens, Greece

    Angelos Hatzakis

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Geretti, A.M., Atkins, M., Nastouli, E., Bradshaw, D. (2021). Laboratory Diagnosis. In: Hatzakis, A. (eds) Hepatitis C: Epidemiology, Prevention and Elimination . Springer, Cham. https://doi.org/10.1007/978-3-030-64649-3_4

Download citation

Publish with us

Policies and ethics

Search

Navigation