Chapter 31 : Molecular Detection and Characterization of Hepatitis C Virus

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Ebook: Choose a downloadable PDF or ePub file. Chapter is a downloadable PDF file. File must be downloaded within 48 hours of purchase

Buy this Chapter
Digital (?) $30.00

Preview this chapter:
Zoom in

Molecular Detection and Characterization of Hepatitis C Virus, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555819071/9781555819088.ch31-1.gif /docserver/preview/fulltext/10.1128/9781555819071/9781555819088.ch31-2.gif


Hepatitis C virus (HCV) and molecular methods are inextricably linked, in history and in clinical practice. This virus was the first to be identified with molecular methods (1) and nucleic acid tests have become fundamentally important in the diagnosis of infection and therapeutic management.

Citation: Forman M, Valsamakis A. 2016. Molecular Detection and Characterization of Hepatitis C Virus, p 430-448. In Persing D, Tenover F, Hayden R, Ieven M, Miller M, Nolte F, Tang Y, van Belkum A (ed), Molecular Microbiology. ASM Press, Washington, DC. doi: 10.1128/9781555819071.ch31
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of FIGURE 1

HCV genome and protein coding scheme. UTR, untranslated region; NS, nonstructural gene; nuc, nucleotide; pos, position; aa, amino acid; gp, glycoprotein. Numbering according to references and .

Citation: Forman M, Valsamakis A. 2016. Molecular Detection and Characterization of Hepatitis C Virus, p 430-448. In Persing D, Tenover F, Hayden R, Ieven M, Miller M, Nolte F, Tang Y, van Belkum A (ed), Molecular Microbiology. ASM Press, Washington, DC. doi: 10.1128/9781555819071.ch31
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 2

Clinical features of acute hepatitis C following exposure to low viral inoculum such as occupational needlestick exposure or community-based exposure ( ). Characteristics following higher dose exposure (transfusion with contaminated blood products) may be different. Intermittent viremia phase estimated from needlestick exposure ( ). Kinetics of other characteristics derived from seroconversion panels ( ). ALT, alanine amino transferase. Dashed lines indicate potential viremia patterns as defined by HCV RNA levels in peripheral blood. Adapted from reference .

Citation: Forman M, Valsamakis A. 2016. Molecular Detection and Characterization of Hepatitis C Virus, p 430-448. In Persing D, Tenover F, Hayden R, Ieven M, Miller M, Nolte F, Tang Y, van Belkum A (ed), Molecular Microbiology. ASM Press, Washington, DC. doi: 10.1128/9781555819071.ch31
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 3

Liver disease progression in chronic hepatitis C. Factors listed in notched arrow accelerate histologic progression of disease.

Citation: Forman M, Valsamakis A. 2016. Molecular Detection and Characterization of Hepatitis C Virus, p 430-448. In Persing D, Tenover F, Hayden R, Ieven M, Miller M, Nolte F, Tang Y, van Belkum A (ed), Molecular Microbiology. ASM Press, Washington, DC. doi: 10.1128/9781555819071.ch31
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 4

Recommended testing algorithm for detection of HCV infection. Derived from reference .

Citation: Forman M, Valsamakis A. 2016. Molecular Detection and Characterization of Hepatitis C Virus, p 430-448. In Persing D, Tenover F, Hayden R, Ieven M, Miller M, Nolte F, Tang Y, van Belkum A (ed), Molecular Microbiology. ASM Press, Washington, DC. doi: 10.1128/9781555819071.ch31
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M. 1989. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science 244:359362[CrossRef].[PubMed]
2. Denniston MM, Jiles RB, Drobeniuc J, Klevens RM, Ward JW, McQuillan GM, Holmberg SD. 2014. Chronic hepatitis C virus infection in the United States, National Health and Nutrition Examination Survey 2003 to 2010. Ann Intern Med 160:293300[CrossRef].[PubMed]
3. Wang CC, Krantz E, Klarquist J, Krows M, McBride L, Scott EP, Shaw-Stiffel T, Weston SJ, Thiede H, Wald A, Rosen HR. 2007. Acute hepatitis C in a contemporary US cohort: modes of acquisition and factors influencing viral clearance. J Infect Dis 196:14741482[CrossRef].[PubMed]
4. Yaphe S, Bozinoff N, Kyle R, Shivkumar S, Pai NP, Klein M. 2012. Incidence of acute hepatitis C virus infection among men who have sex with men with and without HIV infection: a systematic review. Sex Transm Infect 88:558564[CrossRef].[PubMed]
5. Williams IT, Bell BP, Kuhnert W, Alter MJ. 2011. Incidence and transmission patterns of acute hepatitis C in the United States, 1982–2006. Arch Intern Med 171:242248[CrossRef].[PubMed]
6. Xu F, Tong X, Leidner AJ. 2014. Hospitalizations and costs associated with hepatitis C and advanced liver disease continue to increase. Health Aff (Millwood) 33:17281735[CrossRef].[PubMed]
7. Jones CT, Murray CL, Eastman DK, Tassello J, Rice CM. 2007. Hepatitis C virus p7 and NS2 proteins are essential for production of infectious virus. J Virol 81:83748383[CrossRef].[PubMed]
8. Pawlotsky JM. 2013. NS5A inhibitors in the treatment of hepatitis C. J Hepatol 59:375382[CrossRef].[PubMed]
9. Smith DB, Bukh J, Kuiken C, Muerhoff AS, Rice CM, Stapleton JT, Simmonds P. 2014. Expanded classification of hepatitis C virus into 7 genotypes and 67 subtypes: updated criteria and genotype assignment web resource. Hepatology 59:318327[CrossRef].[PubMed]
10. Klevens RM, Hu DJ, Jiles R, Holmberg SD. 2012. Evolving epidemiology of hepatitis C virus in the United States. Clin Infect Dis 55(Suppl 1):S3S9[CrossRef].[PubMed]
11. Suryaprasad AG, White JZ, Xu F, Eichler BA, Hamilton J, Patel A, Hamdounia SB, Church DR, Barton K, Fisher C, Macomber K, Stanley M, Guilfoyle SM, Sweet K, Liu S, Iqbal K, Tohme R, Sharapov U, Kupronis BA, Ward JW, Holmberg SD. 2014. Emerging epidemic of hepatitis C virus infections among young nonurban persons who inject drugs in the United States, 2006–2012. Clin Infect Dis 59:14111419[CrossRef].[PubMed]
12. Park SH, Rehermann B. 2014. Immune responses to HCV and other hepatitis viruses. Immunity 40:1324[CrossRef].[PubMed]
13. Duggal P, Thio CL, Wojcik GL, Goedert JJ, Mangia A, Latanich R, Kim AY, Lauer GM, Chung RT, Peters MG, Kirk GD, Mehta SH, Cox AL, Khakoo SI, Alric L, Cramp ME, Donfield SM, Edlin BR, Tobler LH, Busch MP, Alexander G, Rosen HR, Gao X, Abdel-Hamid M, Apps R, Carrington M, Thomas DL. 2013. Genome-wide association study of spontaneous resolution of hepatitis C virus infection: data from multiple cohorts. Ann Intern Med 158:235245[CrossRef].[PubMed]
14. Rauch A, Kutalik Z, Descombes P, Cai T, Di Iulio J, Mueller T, Bochud M, Battegay M, Bernasconi E, Borovicka J, Colombo S, Cerny A, Dufour JF, Furrer H, Gunthard HF, Heim M, Hirschel B, Malinverni R, Moradpour D, Mullhaupt B, Witteck A, Beckmann JS, Berg T, Bergmann S, Negro F, Telenti A, Bochud PY. 2010. Genetic variation in IL28B is associated with chronic hepatitis C and treatment failure: a genome-wide association study. Gastroenterology 138:1338–1345, 1345.e13311337.
15. Thomas DL, Thio CL, Martin MP, Qi Y, Ge D, O'Huigin C, Kidd J, Kidd K, Khakoo SI, Alexander G, Goedert JJ, Kirk GD, Donfield SM, Rosen HR, Tobler LH, Busch MP, McHutchison JG, Goldstein DB, Carrington M. 2009. Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature 461:798801[CrossRef].[PubMed]
16. Balagopal A, Thomas DL, Thio CL. 2010. IL28B and the control of hepatitis C virus infection. Gastroenterology 139:18651876[CrossRef].[PubMed]
17. Jiménez-Sousa MA, Fernández-Rodríguez A, Guzmán-Fulgencio M, García-Álvarez M, Resino S. 2013. Meta-analysis: implications of interleukin-28B polymorphisms in spontaneous and treatment-related clearance for patients with hepatitis C. BMC Med 11:6[CrossRef].[PubMed]
18. Strader DB, Wright T, Thomas DL, Seeff LB, American Association for the Study of Liver Diseases. 2004. Diagnosis, management, and treatment of hepatitis C. Hepatology 39:11471171[CrossRef].[PubMed]
19. O'Leary JG, Lepe R, Davis GL. 2008. Indications for liver transplantation. Gastroenterology 134:17641776[CrossRef].[PubMed]
20. Adinolfi LE, Utili R, Andreana A, Tripodi MF, Rosario P, Mormone G, Ragone E, Pasquale G, Ruggiero G. 2000. Relationship between genotypes of hepatitis C virus and histopathological manifestations in chronic hepatitis C patients. Eur J Gastroenterol Hepatol 12:299304[CrossRef].[PubMed]
21. Yeo AE, Ghany M, Conry-Cantilena C, Melpolder JC, Kleiner DE, Shih JW, Hoofnagle JH, Alter HJ. 2001. Stability of HCV-RNA level and its lack of correlation with disease severity in asymptomatic chronic hepatitis C virus carriers. J Viral Hepat 8:256263[CrossRef].[PubMed]
22. Yano M, Kumada H, Kage M, Ikeda K, Shimamatsu K, Inoue O, Hashimoto E, Lefkowitch JH, Ludwig J, Okuda K. 1996. The long-term pathological evolution of chronic hepatitis C. Hepatology 23:13341340[CrossRef].[PubMed]
23. Ferreira-Gonzalez A, Shiffman ML. 2004. Use of diagnostic testing for managing hepatitis C virus infection. Semin Liver Dis 24(Suppl 2):918[CrossRef].[PubMed]
24. Carreño V. 2014. Seronegative occult hepatitis C virus infection: clinical implications. J Clin Virol 61:315320[CrossRef].[PubMed]
25. Vidimliski PD, Nikolov I, Geshkovska NM, Dimovski A, Rostaing L, Sikole A. 2014. Review: Occult hepatitis C virus infection: still remains a controversy. J Med Virol 86:14911498[CrossRef].[PubMed]
26. Hoofnagle JH, Mullen KD, Jones DB, Rustgi V, Di Bisceglie A, Peters M, Waggoner JG, Park Y, Jones EA. 1986. Treatment of chronic non-A,non-B hepatitis with recombinant human alpha interferon. A preliminary report. N Engl J Med 315:15751578[CrossRef].[PubMed]
27. Jacobson IM, McHutchison JG, Dusheiko G, Di Bisceglie AM, Reddy KR, Bzowej NH, Marcellin P, Muir AJ, Ferenci P, Flisiak R, George J, Rizzetto M, Shouval D, Sola R, Terg RA, Yoshida EM, Adda N, Bengtsson L, Sankoh AJ, Kieffer TL, George S, Kauffman RS, Zeuzem S, ADVANCE Study Team. 2011. Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med 364:24052416[CrossRef].[PubMed]
28. Poordad F, McCone J Jr, Bacon BR, Bruno S, Manns MP, Sulkowski MS, Jacobson IM, Reddy KR, Goodman ZD, Boparai N, DiNubile MJ, Sniukiene V, Brass CA, Albrecht JK, Bronowicki JP, SPRINT-2 Investigators. 2011. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med 364:11951206[CrossRef].[PubMed]
29. Koh C, Liang TJ. 2014. What is the future of ribavirin therapy for hepatitis C? Antiviral Res 104:3439[CrossRef].[PubMed]
30. Schinazi R, Halfon P, Marcellin P, Asselah T. 2014. HCV direct-acting antiviral agents: the best interferon-free combinations. Liver Int 34(Suppl 1):6978[CrossRef].[PubMed]
31. Farci P, Alter HJ, Wong D, Miller RH, Shih JW, Jett B, Purcell RH. 1991. A long-term study of hepatitis C virus replication in non-A, non-B hepatitis. N Engl J Med 325:98104[CrossRef].[PubMed]
32. Mosley JW, Operskalski EA, Tobler LH, Buskell ZJ, Andrews WW, Phelps B, Dockter J, Giachetti C, Seeff LB, Busch MP, Transfusion-transmitted Viruses Study and Retrovirus Epidemiology Donor Study Groups. 2008. The course of hepatitis C viraemia in transfusion recipients prior to availability of antiviral therapy. J Viral Hepat 15:120128[CrossRef].[PubMed]
33. Thimme R, Oldach D, Chang KM, Steiger C, Ray SC, Chisari FV. 2001. Determinants of viral clearance and persistence during acute hepatitis C virus infection. J Exp Med 194:13951406[CrossRef].[PubMed]
34. Cox AL, Netski DM, Mosbruger T, Sherman SG, Strathdee S, Ompad D, Vlahov D, Chien D, Shyamala V, Ray SC, Thomas DL. 2005. Prospective evaluation of community-acquired acute-phase hepatitis C virus infection. Clin Infect Dis 40:951958[CrossRef].[PubMed]
35. Glynn SA, Wright DJ, Kleinman SH, Hirschkorn D, Tu Y, Heldebrant C, Smith R, Giachetti C, Gallarda J, Busch MP. 2005. Dynamics of viremia in early hepatitis C virus infection. Transfusion 45:9941002[CrossRef].[PubMed]
36. Busch MP. 2001. Insights into the epidemiology, natural history and pathogenesis of hepatitis C virus infection from studies of infected donors and blood product recipients. Transfus Clin Biol 8:200206[CrossRef].[PubMed]
37. Villano SA, Vlahov D, Nelson KE, Cohn S, Thomas DL. 1999. Persistence of viremia and the importance of long-term follow-up after acute hepatitis C infection. Hepatology 29:908914[CrossRef].[PubMed]
38. Mosley JW, Operskalski EA, Tobler LH, Andrews WW, Phelps B, Dockter J, Giachetti C, Busch MP. 2005. Viral and host factors in early hepatitis C virus infection. Hepatology 42:8692[CrossRef].[PubMed]
39. Smith BD, Morgan RL, Beckett GA, Falck-Ytter Y, Holtzman D, Teo CG, Jewett A, Baack B, Rein DB, Patel N, Alter M, Yartel A, Ward JW, Centers for Disease Control and Prevention. 2012. Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945–1965. MMWR Recomm Rep 61(RR-4):132.[PubMed]
40. Kamal SM. 2008. Acute hepatitis C: a systematic review. Am J Gastroenterol 103:12831297, quiz 1298[CrossRef].[PubMed]
41. Chamie G, Bonacini M, Bangsberg DR, Stapleton JT, Hall C, Overton ET, Scherzer R, Tien PC. 2007. Factors associated with seronegative chronic hepatitis C virus infection in HIV infection. Clin Infect Dis 44:577583[CrossRef].[PubMed]
42. Hadlich E, Alvares-Da-Silva MR, Dal Molin RK, Zenker R, Goldani LZ. 2007. Hepatitis C virus (HCV) viremia in HIV-infected patients without HCV antibodies detectable by third-generation enzyme immunoassay. J Gastroenterol Hepatol 22:15061509[CrossRef].[PubMed]
43. Alter MJ, Kuhnert WL, Finelli L, Centers for Disease Control and Prevention. 2003. Guidelines for laboratory testing and result reporting of antibody to hepatitis C virus. MMWR Recomm Rep 52(RR-3):113, 15, quiz CE1–CE4.[PubMed]
44. Papastergiou V, Stampori M, Lisgos P, Pselas C, Prodromidou K, Karatapanis S. 2013. Durability of a sustained virological response, late clinical sequelae, and long-term changes in aspartate aminotransferase to the platelet ratio index after successful treatment with peginterferon/ribavirin for chronic hepatitis C: a prospective study. Eur J Gastroenterol Hepatol 25:798805[CrossRef].[PubMed]
45. Chen J, Florian J, Carter W, Fleischer RD, Hammerstrom TS, Jadhav PR, Zeng W, Murray J, Birnkrant D. 2013. Earlier sustained virologic response end points for regulatory approval and dose selection of hepatitis C therapies. Gastroenterology 144:14501455.e2[CrossRef].[PubMed]
46. Suppiah V, Moldovan M, Ahlenstiel G, Berg T, Weltman M, Abate ML, Bassendine M, Spengler U, Dore GJ, Powell E, Riordan S, Sheridan D, Smedile A, Fragomeli V, Müller T, Bahlo M, Stewart GJ, Booth DR, George J. 2009. IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy. Nat Genet 41:11001104[CrossRef].[PubMed]
47. Tanaka Y, Nishida N, Sugiyama M, Kurosaki M, Matsuura K, Sakamoto N, Nakagawa M, Korenaga M, Hino K, Hige S, Ito Y, Mita E, Tanaka E, Mochida S, Murawaki Y, Honda M, Sakai A, Hiasa Y, Nishiguchi S, Koike A, Sakaida I, Imamura M, Ito K, Yano K, Masaki N, Sugauchi F, Izumi N, Tokunaga K, Mizokami M. 2009. Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C. Nat Genet 41:11051109[CrossRef].[PubMed]
48. Thompson AJ, Muir AJ, Sulkowski MS, Ge D, Fellay J, Shianna KV, Urban T, Afdhal NH, Jacobson IM, Esteban R, Poordad F, Lawitz EJ, McCone J, Shiffman ML, Galler GW, Lee WM, Reindollar R, King JW, Kwo PY, Ghalib RH, Freilich B, Nyberg LM, Zeuzem S, Poynard T, Vock DM, Pieper KS, Patel K, Tillmann HL, Noviello S, Koury K, Pedicone LD, Brass CA, Albrecht JK, Goldstein DB, McHutchison JG. 2010. Interleukin-28B polymorphism improves viral kinetics and is the strongest pretreatment predictor of sustained virologic response in genotype 1 hepatitis C virus. Gastroenterology 139:1209.e18[CrossRef].[PubMed]
49. Mangia A, Mottola L, Santoro R. 2013. Interleukin 28B polymorphisms as predictor of response in hepatitis C virus genotype 2 and 3 infected patients. World J Gastroenterol 19:89248928[CrossRef].[PubMed]
50. Chevaliez S, Bouvier-Alias M, Pawlotsky JM. 2009. Performance of the Abbott real-time PCR assay using m2000sp and m2000rt for hepatitis C virus RNA quantification. J Clin Microbiol 47:17261732[CrossRef].[PubMed]
51. Chevaliez S, Bouvier-Alias M, Brillet R, Pawlotsky JM. 2007. Overestimation and underestimation of hepatitis C virus RNA levels in a widely used real-time polymerase chain reaction-based method. Hepatology 46:2231[CrossRef].[PubMed]
52. Germer JJ, Bommersbach CE, Schmidt DM, Bendel JL, Yao JD. 2009. Quantification of genotype 4 hepatitis C virus RNA by the COBAS AmpliPrep/COBAS TaqMan hepatitis C virus test. Hepatology 50:16791680, author reply 1681[CrossRef].[PubMed]
53. Halfon P, Martinot-Peignoux M, Khiri H, Marcellin P. 2010. Quantification of genotype 4 serum samples: impact of hepatitis C virus genetic variability. Hepatology 52:401[CrossRef].[PubMed]
54. Chevaliez S, Bouvier-Alias M, Rodriguez C, Soulier A, Poveda JD, Pawlotsky JM. 2013. The Cobas AmpliPrep/Cobas TaqMan HCV test, version 2.0, real-time PCR assay accurately quantifies hepatitis C virus genotype 4 RNA. J Clin Microbiol 51:10781082[CrossRef].[PubMed]
55. Zitzer H, Heilek G, Truchon K, Susser S, Vermehren J, Sizmann D, Cobb B, Sarrazin C. 2013. Second-generation Cobas AmpliPrep/Cobas TaqMan HCV quantitative test for viral load monitoring: a novel dual-probe assay design. J Clin Microbiol 51:571577[CrossRef].[PubMed]
56. Lawitz E, Mangia A, Wyles D, Rodriguez-Torres M, Hassanein T, Gordon SC, Schultz M, Davis MN, Kayali Z, Reddy KR, Jacobson IM, Kowdley KV, Nyberg L, Subramanian GM, Hyland RH, Arterburn S, Jiang D, McNally J, Brainard D, Symonds WT, McHutchison JG, Sheikh AM, Younossi Z, Gane EJ. 2013. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med 368:18781887[CrossRef].[PubMed]
57. Lawitz E, Sulkowski MS, Ghalib R, Rodriguez-Torres M, Younossi ZM, Corregidor A, DeJesus E, Pearlman B, Rabinovitz M, Gitlin N, Lim JK, Pockros PJ, Scott JD, Fevery B, Lambrecht T, Ouwerkerk-Mahadevan S, Callewaert K, Symonds WT, Picchio G, Lindsay KL, Beumont M, Jacobson IM. 2014. Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naive patients: the COSMOS randomised study. Lancet 384:17561765[CrossRef].[PubMed]
58. Mallory MA, Lucic DX, Sears MT, Cloherty GA, Hillyard DR. 2014. Evaluation of the Abbott realtime HCV genotype II RUO (GT II) assay with reference to 5′ UTR, core and NS5B sequencing. J Clin Virol 60:2226[CrossRef].[PubMed]
59. González V, Gomes-Fernandes M, Bascuñana E, Casanovas S, Saludes V, Jordana-Lluch E, Matas L, Ausina V, Martró E. 2013. Accuracy of a commercially available assay for HCV genotyping and subtyping in the clinical practice. J Clin Virol 58:249253[CrossRef].[PubMed]
60. Cervinski MA, Sam SS, Steinmetz HB, Wood B, Tsongalis GJ. 2014. Validation of interleukin 28B genotyping assay for clinical use. Clin Biochem 47:478480[CrossRef].[PubMed]
61. Ito K, Higami K, Masaki N, Sugiyama M, Mukaide M, Saito H, Aoki Y, Sato Y, Imamura M, Murata K, Nomura H, Hige S, Adachi H, Hino K, Yatsuhashi H, Orito E, Kani S, Tanaka Y, Mizokami M. 2011. The rs8099917 polymorphism, when determined by a suitable genotyping method, is a better predictor for response to pegylated alpha interferon/ribavirin therapy in Japanese patients than other single nucleotide polymorphisms associated with interleukin-28B. J Clin Microbiol 49:18531860[CrossRef].[PubMed]
62. Melis R, Fauron C, McMillin G, Lyon E, Shirts B, Hubley LM, Slev PR. 2011. Simultaneous genotyping of rs12979860 and rs8099917 variants near the IL28B locus associated with HCV clearance and treatment response. J Mol Diagn 13:446451[CrossRef].[PubMed]
63. Akuta N, Suzuki F, Fukushima T, Kawamura Y, Sezaki H, Suzuki Y, Hosaka T, Kobayashi M, Hara T, Kobayashi M, Saitoh S, Arase Y, Ikeda K, Kumada H. 2014. Utility of detection of telaprevir-resistant variants for prediction of efficacy of treatment of hepatitis C virus genotype 1 infection. J Clin Microbiol 52:193200[CrossRef].[PubMed]
64. Akuta N, Suzuki F, Fukushima T, Kawamura Y, Sezaki H, Suzuki Y, Hosaka T, Kobayashi M, Hara T, Kobayashi M, Saitoh S, Arase Y, Ikeda K, Kumada H. 2013. Prediction of treatment efficacy and telaprevir-resistant variants after triple therapy in patients infected with hepatitis C virus genotype 1. J Clin Microbiol 51:28622868[CrossRef].[PubMed]
65. Sullivan JC, De Meyer S, Bartels DJ, Dierynck I, Zhang EZ, Spanks J, Tigges AM, Ghys A, Dorrian J, Adda N, Martin EC, Beumont M, Jacobson IM, Sherman KE, Zeuzem S, Picchio G, Kieffer TL. 2013. Evolution of treatment-emergent resistant variants in telaprevir phase 3 clinical trials. Clin Infect Dis 57:221229[CrossRef].[PubMed]
66. Forns X, Lawitz E, Zeuzem S, Gane E, Bronowicki JP, Andreone P, Horban A, Brown A, Peeters M, Lenz O, Ouwerkerk-Mahadevan S, Scott J, De La Rosa G, Kalmeijer R, Sinha R, Beumont-Mauviel M. 2014. Simeprevir with peginterferon and ribavirin leads to high rates of SVR in patients with HCV genotype 1 who relapsed after previous therapy: a phase 3 trial. Gastroenterology 146:166979.e3[CrossRef].[PubMed]
67. Schneider MD, Sarrazin C. 2014. Antiviral therapy of hepatitis C in 2014: do we need resistance testing? Antiviral Res 105:6471[CrossRef].[PubMed]
68. Busch MP, Glynn SA, Stramer SL, Strong DM, Caglioti S, Wright DJ, Pappalardo B, Kleinman SH, NHLBI-REDS NAT Study Group. 2005. A new strategy for estimating risks of transfusion-transmitted viral infections based on rates of detection of recently infected donors. Transfusion 45:254264[CrossRef].[PubMed]
69. Zou S, Dorsey KA, Notari EP, Foster GA, Krysztof DE, Musavi F, Dodd RY, Stramer SL. 2010. Prevalence, incidence, and residual risk of human immunodeficiency virus and hepatitis C virus infections among United States blood donors since the introduction of nucleic acid testing. Transfusion 50:14951504[CrossRef].[PubMed]
70. Stramer SL, Krysztof DE, Brodsky JP, Fickett TA, Reynolds B, Dodd RY, Kleinman SH. 2013. Comparative analysis of triplex nucleic acid test assays in United States blood donors. Transfusion 53:25252537[CrossRef].[PubMed]
71. Laperche S, Bouchardeau F, Thibault V, Pozzetto B, Vallet S, Rosenberg AR, Roque-Afonso AM, Gassin M, Stoll-Keller F, Trimoulet P, Gault E, Chanzy B, Mercier B, Branger M, Pawlotsky JM, Henquell C, Lunel F, Gaudy-Graffin C, Alain S, Chaix ML, Duverlie G, Izopet J, Lefrère JJ. 2007. Multicenter trials need to use the same assay for hepatitis C virus viral load determination. J Clin Microbiol 45:37883790[CrossRef].[PubMed]
72. Michelin BD, Muller Z, Stelzl E, Marth E, Kessler HH. 2007. Evaluation of the Abbott RealTime HCV assay for quantitative detection of hepatitis C virus RNA. J Clin Virol 38:96100[CrossRef].[PubMed]
73. Pyne MT, Konnick EQ, Phansalkar A, Hillyard DR. 2009. Evaluation of the Abbott investigational use only RealTime hepatitis C virus (HCV) assay and comparison to the Roche TaqMan HCV analyte-specific reagent assay. J Clin Microbiol 47:28722878[CrossRef].[PubMed]
74. Colson P, Motte A, Tamalet C. 2006. Broad differences between the COBAS ampliprep total nucleic acid isolation-COBAS TaqMan 48 hepatitis C virus (HCV) and COBAS HCV monitor v2.0 assays for quantification of serum HCV RNA of non-1 genotypes. J Clin Microbiol 44:16021603[CrossRef].[PubMed]
75. Martinot-Peignoux M, Khiri H, Leclere L, Maylin S, Marcellin P, Halfon P. 2009. Clinical performances of two real-time PCR assays and bDNA/TMA to early monitor treatment outcome in patients with chronic hepatitis C. J Clin Virol 46:216221[CrossRef].[PubMed]
76. Pisani G, Cristiano K, Marino F, Luciani F, Bisso GM, Mele C, Adriani D, Gentili G, Wirz M. 2009. Quantification of hepatitis C virus (HCV) RNA in a multicenter study: implications for management of HCV genotype 1-infected patients. J Clin Microbiol 47:29312936[CrossRef].[PubMed]
77. Tuaillon E, Mondain AM, Ottomani L, Roudière L, Perney P, Picot MC, Séguret F, Blanc F, Larrey D, Van de Perre P, Ducos J. 2007. Impact of hepatitis C virus (HCV) genotypes on quantification of HCV RNA in serum by COBAS AmpliPrep/COBAS TaqMan HCV test, Abbott HCV realtime assay [corrected] and VERSANT HCV RNA assay. J Clin Microbiol 45:30773081[CrossRef].[PubMed]
78. Vermehren J, Kau A, Gärtner BC, Göbel R, Zeuzem S, Sarrazin C. 2008. 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 46:38803891[CrossRef].[PubMed]
79. Ogawa E, Furusyo N, Murata M, Toyoda K, Eiraku K, Shimizu M, Harada Y, Mitsumoto F, Takayama K, Okada K, Kainuma M, Hayashi J. 2013. Early phase viral kinetics of chronic hepatitis C patients receiving telaprevir-based triple therapy: a comparison of two real-time PCR assays. Antiviral Res 99:119124[CrossRef].[PubMed]
80. Taylor N, Haschke-Becher E, Greil R, Strasser M, Oberkofler H. 2014. Performance characteristics of the COBAS Ampliprep/COBAS TaqMan v2.0 and the Abbott RealTime hepatitis C assays—implications for response-guided therapy in genotype 1 infections. Antivir Ther 19:449454[CrossRef].[PubMed]
81. Vermehren J, Aghemo A, Falconer K, Susser S, Lunghi G, Zeuzem S, Colombo M, Weiland O, Sarrazin C. 2014. Clinical significance of residual viremia detected by two real-time PCR assays for response-guided therapy of HCV genotype 1 infection. J Hepatol 60:913919[CrossRef].[PubMed]
82. Harrington PR, Zeng W, Naeger LK. 2012. Clinical relevance of detectable but not quantifiable hepatitis C virus RNA during boceprevir or telaprevir treatment. Hepatology 55:10481057[CrossRef].[PubMed]
83. Choo QL, Richman KH, Han JH, Berger K, Lee C, Dong C, Gallegos C, Coit D, Medina-Selby R, Barr PJ. 1991. Genetic organization and diversity of the hepatitis C virus. Proc Natl Acad Sci USA 88:24512455[CrossRef].[PubMed]
84. Major ME, Feinstone SM. 1997. The molecular virology of hepatitis C. Hepatology 25:15271538[CrossRef].[PubMed]
85. Maheshwari A, Ray S, Thuluvath PJ. 2008. Acute hepatitis C. Lancet 372:321332[CrossRef].[PubMed]
86. Sulkowski MS, Ray SC, Thomas DL. 2002. Needlestick transmission of hepatitis C. JAMA 287:24062413[CrossRef].[PubMed]
87. Centers for Disease Control and Prevention (CDC). 2013. Testing for HCV infection: an update of guidance for clinicians and laboratorians. MMWR Morb Mortal Wkly Rep 62:362365.[PubMed]
88. Afdhal N, Reddy KR, Nelson DR, Lawitz E, Gordon SC, Schiff E, Nahass R, Ghalib R, Gitlin N, Herring R, Lalezari J, Younes ZH, Pockros PJ, Di Bisceglie AM, Arora S, Subramanian GM, Zhu Y, Dvory-Sobol H, Yang JC, Pang PS, Symonds WT, McHutchison JG, Muir AJ, Sulkowski M, Kwo P, ION-2 Investigators. 2014. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med 370:14831493[CrossRef].[PubMed]
89. Afdhal N, Zeuzem S, Kwo P, Chojkier M, Gitlin N, Puoti M, Romero-Gomez M, Zarski JP, Agarwal K, Buggisch P, Foster GR, Bräu N, Buti M, Jacobson IM, Subramanian GM, Ding X, Mo H, Yang JC, Pang PS, Symonds WT, McHutchison JG, Muir AJ, Mangia A, Marcellin P, ION-1 Investigators. 2014. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med 370:18891898[CrossRef].[PubMed]
90. Feld JJ, Kowdley KV, Coakley E, Sigal S, Nelson DR, Crawford D, Weiland O, Aguilar H, Xiong J, Pilot-Matias T, DaSilva-Tillmann B, Larsen L, Podsadecki T, Bernstein B. 2014. Treatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. N Engl J Med 370:15941603[CrossRef].[PubMed]
91. Ferenci P, Bernstein D, Lalezari J, Cohen D, Luo Y, Cooper C, Tam E, Marinho RT, Tsai N, Nyberg A, Box TD, Younes Z, Enayati P, Green S, Baruch Y, Bhandari BR, Caruntu FA, Sepe T, Chulanov V, Janczewska E, Rizzardini G, Gervain J, Planas R, Moreno C, Hassanein T, Xie W, King M, Podsadecki T, Reddy KR, PEARL-III Study, PEARL-IV Study. 2014. ABT-450/r-ombitasvir and dasabuvir with or without ribavirin for HCV. N Engl J Med 370:19831992[CrossRef].[PubMed]
92. Zeuzem S, Dusheiko GM, Salupere R, Mangia A, Flisiak R, Hyland RH, Illeperuma A, Svarovskaia E, Brainard DM, Symonds WT, Subramanian GM, McHutchison JG, Weiland O, Reesink HW, Ferenci P, Hézode C, Esteban R, VALENCE Investigators. 2014. Sofosbuvir and ribavirin in HCV genotypes 2 and 3. N Engl J Med 370:19932001[CrossRef].[PubMed]
93. Sizmann D, Boeck C, Boelter J, Fischer D, Miethke M, Nicolaus S, Zadak M, Babiel R. 2007. Fully automated quantification of hepatitis C virus (HCV) RNA in human plasma and human serum by the COBAS AmpliPrep/COBAS TaqMan system. J Clin Virol 38:326333[CrossRef].[PubMed]
94. Colucci G, Ferguson J, Harkleroad C, Lee S, Romo D, Soviero S, Thompson J, Velez M, Wang A, Miyahara Y, Young S, Sarrazin C. 2007. Improved COBAS TaqMan hepatitis C virus test (Version 2.0) for use with the High Pure system: enhanced genotype inclusivity and performance characteristics in a multisite study. J Clin Microbiol 45:35953600[CrossRef].[PubMed]
95. Sábato MF, Shiffman ML, Langley MR, Wilkinson DS, Ferreira-Gonzalez A. 2007. Comparison of performance characteristics of three real-time reverse transcription-PCR test systems for detection and quantification of hepatitis C virus. J Clin Microbiol 45:25292536[CrossRef].[PubMed]
96. Caliendo AM, Valsamakis A, Zhou Y, Yen-Lieberman B, Andersen J, Young S, Ferreira-Gonzalez A, Tsongalis GJ, Pyles R, Bremer JW, Lurain NS. 2006. Multilaboratory comparison of hepatitis C virus viral load assays. J Clin Microbiol 44:17261732[CrossRef].[PubMed]
97. Chevaliez S, Bouvier-Alias M, Pawlotsky JM, Pawlotsky JM. 2009. Performance of the Abbott real-time PCR assay using m2000sp and m2000rt for hepatitis C virus RNA quantification. J Clin Microbiol 47:17261732[CrossRef].[PubMed]
98. Elbeik T, Surtihadi J, Destree M, Gorlin J, Holodniy M, Jortani SA, Kuramoto K, Ng V, Valdes R Jr, Valsamakis A, Terrault NA. 2004. Multicenter evaluation of the performance characteristics of the bayer VERSANT HCV RNA 3.0 assay (bDNA). J Clin Microbiol 42:563569[CrossRef].[PubMed]
99. Sam SS, Steinmetz HB, Tsongalis GJ, Tafe LJ, Lefferts JA. 2013. Validation of a solid-phase electrochemical array for genotyping hepatitis C virus. Exp Mol Pathol 95:1822[CrossRef].[PubMed]
100. Nolte FS, Green AM, Fiebelkorn KR, Caliendo AM, Sturchio C, Grunwald A, Healy M. 2003. Clinical evaluation of two methods for genotyping hepatitis C virus based on analysis of the 5′ noncoding region. J Clin Microbiol 41:15581564[CrossRef].[PubMed]
101. Bouchardeau F, Cantaloube JF, Chevaliez S, Portal C, Razer A, Lefrère JJ, Pawlotsky JM, De Micco P, Laperche S. 2007. Improvement of hepatitis C virus (HCV) genotype determination with the new version of the INNO-LiPA HCV assay. J Clin Microbiol 45:11401145[CrossRef].[PubMed]
102. Stelzl E, van der Meer C, Gouw R, Beld M, Grahovac M, Marth E, Kessler HH. 2007. Determination of the hepatitis C virus subtype: comparison of sequencing and reverse hybridization assays. Clin Chem Lab Med 45:167170[CrossRef].[PubMed]
103. Verbeeck J, Stanley MJ, Shieh J, Celis L, Huyck E, Wollants E, Morimoto J, Farrior A, Sablon E, Jankowski-Hennig M, Schaper C, Johnson P, Van Ranst M, Van Brussel M. 2008. Evaluation of Versant hepatitis C virus genotype assay (LiPA) 2.0. J Clin Microbiol 46:19011906[CrossRef].[PubMed]
104. Germer JJ, Majewski DW, Yung B, Mitchell PS, Yao JD. 2006. Evaluation of the invader assay for genotyping hepatitis C virus. J Clin Microbiol 44:318323[CrossRef].[PubMed]
105. Martró E, González V, Buckton AJ, Saludes V, Fernández G, Matas L, Planas R, Ausina V. 2008. Evaluation of a new assay in comparison with reverse hybridization and sequencing methods for hepatitis C virus genotyping targeting both 5′ noncoding and nonstructural 5b genomic regions. J Clin Microbiol 46:192197[CrossRef].[PubMed]
106. Margraf RL, Page S, Erali M, Wittwer CT. 2004. Single-tube method for nucleic acid extraction, amplification, purification, and sequencing. Clin Chem 50:17551761[CrossRef].[PubMed]
107. Murphy DG, Willems B, Deschênes M, Hilzenrat N, Mousseau R, Sabbah S. 2007. Use of sequence analysis of the NS5B region for routine genotyping of hepatitis C virus with reference to C/E1 and 5′ untranslated region sequences. J Clin Microbiol 45:11021112[CrossRef].[PubMed]
108. Ross RS, Viazov S, Wolters B, Roggendorf M. 2008. Towards a better resolution of hepatitis C virus variants: CLIP sequencing of an HCV core fragment and automated assignment of genotypes and subtypes. J Virol Methods 148:2533[CrossRef].[PubMed]
109. van Doorn LJ, Kleter B, Pike I, Quint W. 1996. Analysis of hepatitis C virus isolates by serotyping and genotyping. J Clin Microbiol 34:17841787.[PubMed]
110. Huang RY, Chang HT, Lan CY, Pai TW, Wu CN, Ling CM, Chang MD. 2008. Development and evaluation of a sensitive enzyme-linked oligonucleotide-sorbent assay for detection of polymerase chain reaction-amplified hepatitis C virus of genotypes 1–6. J Virol Methods 151:211216[CrossRef].[PubMed]
111. Mao H, Lu Z, Zhang H, Liu K, Zhao J, Jin G, Gu S, Yang M. 2008. Colorimetric oligonucleotide array for genotyping of hepatitis C virus based on the 5′ non-coding region. Clin Chim Acta 388:2227[CrossRef].[PubMed]
112. Davidson F, Simmonds P, Ferguson JC, Jarvis LM, Dow BC, Follett EAC, Seed CRG, Krusius T, Lin C, Medgyesi GA, Kiyokawa H, Olim G, Duraisamy G, Cuypers T, Saeed AA, Teo D, Conradie J, Kew MC, Lin M, Nuchaprayoon C, Ndimbie OK, Yap PL. 1995. Survey of major genotypes and subtypes of hepatitis C virus using RFLP of sequences amplified from the 5′ non-coding region. J Gen Virol 76:11971204[CrossRef].[PubMed]
113. Nakao T, Enomoto N, Takada N, Takada A, Date T. 1991. Typing of hepatitis C virus genomes by restriction fragment length polymorphism. J Gen Virol 72:21052112[CrossRef].[PubMed]
114. Margraf RL, Erali M, Liew M, Wittwer CT. 2004. Genotyping hepatitis C virus by heteroduplex mobility analysis using temperature gradient capillary electrophoresis. J Clin Microbiol 42:45454551[CrossRef].[PubMed]
115. White PA, Zhai X, Carter I, Zhao Y, Rawlinson WD. 2000. Simplified hepatitis C virus genotyping by heteroduplex mobility analysis. J Clin Microbiol 38:477482.[PubMed]
116. Antonishyn NA, Ast VM, McDonald RR, Chaudhary RK, Lin L, Andonov AP, Horsman GB. 2005. Rapid genotyping of hepatitis C virus by primer-specific extension analysis. J Clin Microbiol 43:51585163[CrossRef].[PubMed]
117. Hu YW, Balaskas E, Furione M, Yen PH, Kessler G, Scalia V, Chui L, Sher G. 2000. Comparison and application of a novel genotyping method, semiautomated primer-specific and mispair extension analysis, and four other genotyping assays for detection of hepatitis C virus mixed-genotype infections. J Clin Microbiol 38:28072813.[PubMed]
118. Ohno O, Mizokami M, Wu RR, Saleh MG, Ohba K, Orito E, Mukaide M, Williams R, Lau JY. 1997. New hepatitis C virus (HCV) genotyping system that allows for identification of HCV genotypes 1a, 1b, 2a, 2b, 3a, 3b, 4, 5a, and 6a. J Clin Microbiol 35:201207.[PubMed]
119. Okamoto H, Kobata S, Tokita H, Inoue T, Woodfield GD, Holland PV, Al-Knawy BA, Uzunalimoglu O, Miyakawa Y, Mayumi M. 1996. A second-generation method of genotyping hepatitis C virus by the polymerase chain reaction with sense and antisense primers deduced from the core gene. J Virol Methods 57:3145[CrossRef].[PubMed]
120. Alfaresi MS, Elkoush AA. 2007. Determination of hepatitis C virus genotypes by melting-curve analysis of quantitative polymerase chain reaction products. Indian J Med Microbiol 25:249252[CrossRef].[PubMed]
121. Lindh M, Hannoun C. 2005. Genotyping of hepatitis C virus by Taqman real-time PCR. J Clin Virol 34:108114[CrossRef].[PubMed]
122. Moghaddam A, Reinton N, Dalgard O. 2006. A rapid real-time PCR assay for determination of hepatitis C virus genotypes 1, 2 and 3a. J Viral Hepat 13:222229[CrossRef].[PubMed]
123. Rolfe KJ, Alexander GJ, Wreghitt TG, Parmar S, Jalal H, Curran MD. 2005. A real-time Taqman method for hepatitis C virus genotyping. J Clin Virol 34:115121[CrossRef].[PubMed]
124. Schröter M, Zöllner B,