Hepatitis C virus: Virology, diagnosis and treatment

World Journal of Hepatology

Volumn 7, Issue 10, 2015, Pages 1377-1389

  Li, Hui Chun ^a   Lo, Shih Yen ^a,b  

^a TZU CHI UNIVERSITY   (Taiwan)

^b BUDDHIST TZU CHI GENERAL HOSPITAL   (Taiwan)

Author keywords

Diagnosis; Direct acting antivirals; Enzyme immunoassay; Hepatitis C virus; Hepatocellular carcinoma; Hosttargeted agents; Interferon; Nucleic acid test; Sofosbuvir; Treatment

Indexed keywords

EID: 84930398412     PISSN: None     EISSN: 19485182     Source Type: Journal    
DOI: 10.4254/wjh.v7.i10.1377     Document Type: Review

References (113)

1. Alberti A, Chemello L, Benvegnù L. Natural history of hepatitis C. J Hepatol 1999; 31 Suppl 1: 17-24 [PMID: 10622555 DOI: 10.1016/S0168-8278(99)80369-9].
2. Hoofnagle JH. Course and outcome of hepatitis C. Hepatology 2002; 36: S21-S29 [PMID: 12407573 DOI: 10.1053/jhep. 2002.36227].
3. Chen SL, Morgan TR. The natural history of hepatitis C virus (HCV) infection. Int J Med Sci 2006; 3: 47-52 [PMID: 16614742 DOI: 10.7150/ijms.3.47].
4. Carrozzo M, Scally K. Oral manifestations of hepatitis C virus infection. World J Gastroenterol 2014; 20: 7534-7543 [PMID: 24976694 DOI: 10.3748/wjg.v20.i24.7534].
5. Ozkok A, Yildiz A. Hepatitis C virus associated glomerulopathies. World J Gastroenterol 2014; 20: 7544-7554 [PMID: 24976695 DOI: 10.3748/wjg.v20.i24.7544].
6. Grimbert S, Valensi P, Lévy-Marchal C, Perret G, Richardet JP, Raffoux C, Trinchet JC, Beaugrand M. High prevalence of diabetes mellitus in patients with chronic hepatitis C. A case-control study. Gastroenterol Clin Biol 1996; 20: 544-548 [PMID: 8881566].
7. Montenegro L, De Michina A, Misciagna G, Guerra V, Di Leo A. Virus C hepatitis and type 2 diabetes: a cohort study in southern Italy. Am J Gastroenterol 2013; 108: 1108-1111 [PMID: 23567360 DOI: 10.1038/ajg.2013.90].
8. Rau M, Baur K, Geier A. Host genetic variants in the pathogenesis of hepatitis C. Viruses 2012; 4: 3281-3302 [PMID: 23342360 DOI: 10.3390/v4123281].
9. Saito T, Ueno Y. Transmission of hepatitis C virus: self-limiting hepatitis or chronic hepatitis?. World J Gastroenterol 2013; 19: 6957-6961 [PMID: 24222939 DOI: 10.3748/wjg.v19.i41.6957].
10. Timm J, Roggendorf M. Sequence diversity of hepatitis C virus: implications for immune control and therapy. World J Gastroenterol 2007; 13: 4808-4817 [PMID: 17828811].
11. Kato N, Hijikata M, Ootsuyama Y, Nakagawa M, Ohkoshi S, Shimotohno K. Sequence diversity of hepatitis C viral genomes. Mol Biol Med 1990; 7: 495-501 [PMID: 1963917].
12. Gómez J, Martell M, Quer J, Cabot B, Esteban JI. Hepatitis C viral quasispecies. J Viral Hepat 1999; 6: 3-16 [PMID: 10847126 DOI: 10.1046/j.1365-2893.1999.t01-1-6120131.x].
13. Chayama K, Hayes CN. Hepatitis C virus: How genetic variability affects pathobiology of disease. J Gastroenterol Hepatol 2011; 26 Suppl 1: 83-95 [PMID: 21199518 DOI: 10.1111/j. 1440-1746.2010. 06550.x].
14. Wang Y. Scotomas in molecular virology and epidemiology of hepatitis C virus. World J Gastroenterol 2013; 19: 7910-7921 [PMID: 24307785 DOI: 10.3748/wjg.v19.i44.7910].
15. Bukh J, Miller RH, Purcell RH. Genetic heterogeneity of hepatitis C virus: quasispecies and genotypes. Semin Liver Dis 1995; 15: 41-63 [PMID: 7597443 DOI: 10.1055/s-2007-1007262].
16. Simmonds P. Genetic diversity and evolution of hepatitis C virus-15 years on. J Gen Virol 2004; 85: 3173-3188 [PMID: 15483230 DOI: 10.1099/vir.0.80401-0].
17. Gower E, Estes C, Blach S, Razavi-Shearer K, Razavi H. Global epidemiology and genotype distribution of the hepatitis C virus infection. J Hepatol 2014; 61: S45-S57 [PMID: 25086286 DOI: 10.1016/j.jhep.2014.07.027].
18. Messina JP, Humphreys I, Flaxman A, Brown A, Cooke GS, Pybus OG, Barnes E. Global distribution and prevalence of hepatitis C virus genotypes. Hepatology 2015; 61: 77-87 [PMID: 25069599 DOI: 10.1002/hep.27259].
19. Chevaliez S, Pawlotsky JM. Hepatitis C virus: virology, diagnosis and management of antiviral therapy. World J Gastroenterol 2007; 13: 2461-2466 [PMID: 17552030 DOI: 10.3748/wjg.v13.i17.2461].
20. El-Shamy A, Hotta H. Impact of hepatitis C virus heterogeneity on interferon sensitivity: an overview. World J Gastroenterol 2014; 20: 7555-7569 [PMID: 24976696 DOI: 10.3748/wjg.v20.i24.7555].
21. Scheel TK, Rice CM. Understanding the hepatitis C virus life cycle paves the way for highly effective therapies. Nat Med 2013; 19: 837-849 [PMID: 23836234 DOI: 10.1038/nm.3248].
22. Lemon SM, Walker C, Alter MJ, Yi M. Hepatitis C virus. In: Knipe DM, Howley PM, editors. Field Virology. Philadelphia: Lippincott Williams and Wilkins, 2007: 1253-1304.
23. Chevaliez S, Pawlotsky JM. Virology of hepatitis C virus infection. Best Pract Res Clin Gastroenterol 2012; 26: 381-389 [PMID: 23199498 DOI: 10.1016/j.bpg.2012.09.006].
24. Catanese MT, Uryu K, Kopp M, Edwards TJ, Andrus L, Rice WJ, Silvestry M, Kuhn RJ, Rice CM. Ultrastructural analysis of hepatitis C virus particles. Proc Natl Acad Sci USA 2013; 110: 9505-9510 [PMID: 23690609 DOI: 10.1073/pnas.1307527110].
25. Zhu YZ, Qian XJ, Zhao P, Qi ZT. How hepatitis C virus invades hepatocytes: the mystery of viral entry. World J Gastroenterol 2014; 20: 3457-3467 [PMID: 24707128 DOI: 10.3748/wjg.v20. i13.3457].
26. Gu M, Rice CM. Structures of hepatitis C virus nonstructural proteins required for replicase assembly and function. Curr Opin Virol 2013; 3: 129-136 [PMID: 23601958 DOI: 10.1016/j.coviro.2013.03.013].
27. Bartenschlager R, Lohmann V, Penin F. The molecular and structural basis of advanced antiviral therapy for hepatitis C virus infection. Nat Rev Microbiol 2013; 11: 482-496 [PMID: 23748342 DOI: 10.1038/nrmicro3046].
28. Pawlotsky JM. Hepatitis C virus: standard-of-care treatment. Adv Pharmacol 2013; 67: 169-215 [PMID: 23886001 DOI: 10.1016/B978-0-12-405880-4.00005-6].
29. Pawlotsky JM. What are the pros and cons of the use of hosttargeted agents against hepatitis C?. Antiviral Res 2014; 105: 22-25 [PMID: 24583032 DOI: 10.1016/j.antiviral.2014.02.008].
30. Bartenschlager R, Penin F, Lohmann V, André P. Assembly of infectious hepatitis C virus particles. Trends Microbiol 2011; 19: 95-103 [PMID: 21146993 DOI: 10.1016/j.tim.2010.11.005].
31. Lin CC, Tsai P, Sun HY, Hsu MC, Lee JC, Wu IC, Tsao CW, Chang TT, Young KC. Apolipoprotein J, a glucose-upregulated molecular chaperone, stabilizes core and NS5A to promote infectious hepatitis C virus virion production. J Hepatol 2014; 61: 984-993 [PMID: 24996046].
32. Penin F, Dubuisson J, Rey FA, Moradpour D, Pawlotsky JM. Structural biology of hepatitis C virus. Hepatology 2004; 39: 5-19 [PMID: 14752815 DOI: 10.1002/hep.20032].
33. Li HC, Ma HC, Yang CH, Lo SY. Production and pathogenicity of hepatitis C virus core gene products. World J Gastroenterol 2014; 20: 7104-7122 [PMID: 24966583 DOI: 10.3748/wjg.v20.i23.7104].
34. Bakulin I, Pasechnikov V, Varlamicheva A, Sannikova I. NS3 protease inhibitors for treatment of chronic hepatitis C: Efficacy and safety. World J Hepatol 2014; 6: 326-339 [PMID: 24868326 DOI: 10.4254/wjh.v6.i5.326].
35. Chevaliez S, Pawlotsky JM. How to use virological tools for optimal management of chronic hepatitis C. Liver Int 2009; 29 Suppl 1: 9-14 [PMID: 19207960 DOI: 10.1111/j. 1478-3231.2008.0 1926.x].
36. Sagnelli E, Coppola N, Marrocco C, Coviello G, Rossi G, Battaglia M, Sagnelli C, Messina V, Tonziello A, Scolastico C, Filippini P. Diagnosis of HCV related acute hepatitis by serial determination of IgM to HCV: a preliminary observation. J Biol Regul Homeost Agents 2003; 17: 207-210 [PMID: 14518726].
37. Farci P, Alter HJ, Govindarajan S, Wong DC, Engle R, Lesniewski RR, Mushahwar IK, Desai SM, Miller RH, Ogata N. Lack of protective immunity against reinfection with hepatitis C virus. Science 1992; 258: 135-140 [PMID: 1279801 DOI: 10.1126/science.1279801].
38. Yuki N, Hayashi N, Ohkawa K, Hagiwara H, Oshita M, Katayama K, Sasaki Y, Kasahara A, Fusamoto H, Kamada T. The significance of immunoglobulin M antibody response to hepatitis C virus core protein in patients with chronic hepatitis C. Hepatology 1995; 22: 402-406 [PMID: 7543432].
39. Albertoni G, Castelo Girão MJ, Schor N. Mini review: current molecular methods for the detection and quantification of hepatitis B virus, hepatitis C virus, and human immunodeficiency virus type 1. Int J Infect Dis 2014; 25: 145-149 [PMID: 24927665 DOI: 10.1016/j.ijid.2014.04.007].
40. Campos-Outcalt D. Hepatitis C: new CDC screening recommendations. J Fam Pract 2012; 61: 744-746 [PMID: 23313992].
41. Chevaliez S, Pawlotsky JM. Diagnosis and management of chronic viral hepatitis: antigens, antibodies and viral genomes. Best Pract Res Clin Gastroenterol 2008; 22: 1031-1048 [PMID: 19187865 DOI: 10.1016/j.bpg.2008.11.004].
42. Chevaliez S, Pawlotsky JM. Virological techniques for the diagnosis and monitoring of hepatitis B and C. Ann Hepatol 2009; 8: 7-12 [PMID: 19221527].
43. Gupta E, Bajpai M, Choudhary A. Hepatitis C virus: Screening, diagnosis, and interpretation of laboratory assays. Asian J Transfus Sci 2014; 8: 19-25 [PMID: 24678168 DOI: 10.4103/0973-6247.12 6683].
44. Tillmann HL. Hepatitis C virus core antigen testing: role in diagnosis, disease monitoring and treatment. World J Gastroenterol 2014; 20: 6701-6706 [PMID: 24944462 DOI: 10.3748/wjg.v20. i22.6701].
45. Alborino F, Burighel A, Tiller FW, van Helden J, Gabriel C, Raineri A, Catapano R, Stekel H. Multicenter evaluation of a fully automated third-generation anti-HCV antibody screening test with excellent sensitivity and specificity. Med Microbiol Immunol 2011; 200: 77-83 [PMID: 20865278 DOI: 10.1007/s00430-010-0171-0].
46. 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 [PMID: 11264728].
47. Mack CL, Gonzalez-Peralta RP, Gupta N, Leung D, Narkewicz MR, Roberts EA, Rosenthal P, Schwarz KB. NASPGHAN practice guidelines: Diagnosis and management of hepatitis C infection in infants, children, and adolescents. J Pediatr Gastroenterol Nutr 2012; 54: 838-855 [PMID: 22487950 DOI: 10.1097/MPG.0b013e318258328d].
48. Barrera JM, Francis B, Ercilla G, Nelles M, Achord D, Darner J, Lee SR. Improved detection of anti-HCV in post-transfusion hepatitis by a third-generation ELISA. Vox Sang 1995; 68: 15-18 [PMID: 7536987 DOI: 10.1111/j.1423-0410.1995.tb02538.x].
49. Saludes V, González V, Planas R, Matas L, Ausina V, Martró E. Tools for the diagnosis of hepatitis C virus infection and hepatic fibrosis staging. World J Gastroenterol 2014; 20: 3431-3442 [PMID: 24707126 DOI: 10.3748/wjg.v20.i13.3431].
50. Scalioni Lde P, Cruz HM, de Paula VS, Miguel JC, Marques VA, Villela-Nogueira CA, Milagres FA, Cruz MS, Bastos FI, Andrade TM, Motta-Castro AR, Lewis-Ximenez LL, Lampe E, Villar LM. Performance of rapid hepatitis C virus antibody assays among high-and low-risk populations. J Clin Virol 2014; 60: 200-205 [PMID: 24794796 DOI: 10.1016/j.jcv.2014.04.001].
51. Shivkumar S, Peeling R, Jafari Y, Joseph L, Pant Pai N. Accuracy of rapid and point-of-care screening tests for hepatitis C: a systematic review and meta-analysis. Ann Intern Med 2012; 157: 558-566 [PMID: 23070489 DOI: 10.7326/0003-4819-157-8-20121 0160-00006].
52. Lee SR, Kardos KW, Schiff E, Berne CA, Mounzer K, Banks AT, Tatum HA, Friel TJ, Demicco MP, Lee WM, Eder SE, Monto A, Yearwood GD, Guillon GB, Kurtz LA, Fischl M, Unangst JL, Kriebel L, Feiss G, Roehler M. Evaluation of a new, rapid test for detecting HCV infection, suitable for use with blood or oral fluid. J Virol Methods 2011; 172: 27-31 [PMID: 21182871 DOI: 10.1016/j.jviromet.2010.12.009].
53. Martin P, Fabrizi F, Dixit V, Quan S, Brezina M, Kaufman E, Sra K, DiNello R, Polito A, Gitnick G. Automated RIBA hepatitis C virus (HCV) strip immunoblot assay for reproducible HCV diagnosis. J Clin Microbiol 1998; 36: 387-390 [PMID: 9466746].
54. Persing DH, Landry ML. In vitro amplification techniques for the detection of nucleic acids: new tools for the diagnostic laboratory. Yale J Biol Med 1989; 62: 159-171 [PMID: 2672619].
55. Irshad M, Mankotia DS, Irshad K. An insight into the diagnosis and pathogenesis of hepatitis C virus infection. World J Gastroenterol 2013; 19: 7896-7909 [PMID: 24307784 DOI: 10.3748/wjg.v19. i44.7896].
56. Shiffman ML, Ferreira-Gonzalez A, Reddy KR, Sterling RK, Luketic VA, Stravitz RT, Sanyal AJ, Garrett CT, De Medina M, Schiff ER. Comparison of three commercially available assays for HCV RNA using the international unit standard: implications for management of patients with chronic hepatitis C virus infection in clinical practice. Am J Gastroenterol 2003; 98: 1159-1166 [PMID: 12809843 DOI: 10.1111/j.1572-0241.2003.07449.x].
57. Pawlotsky JM. Use and interpretation of virological tests for hepatitis C. Hepatology 2002; 36: S65-S73 [PMID: 12407578 DOI: 10.1053/jhep.2002.36815].
58. Chevaliez S, Bouvier-Alias M, Castéra L, Pawlotsky JM. The Cobas AmpliPrep-Cobas TaqMan real-time polymerase chain reaction assay fails to detect hepatitis C virus RNA in highly viremic genotype 4 clinical samples. Hepatology 2009; 49: 1397-1398 [PMID: 19330876 DOI: 10.1002/hep.22767].
59. Chevaliez S, Bouvier-Alias M, Rodriguez C, Soulier A, Poveda JD, Pawlotsky JM. 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 2013; 51: 1078-1082 [PMID: 23325825 DOI: 10.1128/JCM.02004-12].
60. Butcher A, Aslam S, Hemyari P, Cowen U, Heilek G. HCV RNA detection in HCV antibody-positive patients with the COBAS AmpliPrep/COBAS TaqMan HCV test, v2.0 in comparison with FDA-approved nucleic acid tests. J Clin Virol 2014; 60: 336-340 [PMID: 24881014 DOI: 10.1016/j.jcv.2014.04.018].
61. Pawlotsky JM. More sensitive hepatitis C virus RNA detection: what for?. J Hepatol 2010; 52: 783-785 [PMID: 20385426 DOI: 10.1016/j.jhep.2010.02.007].
62. 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: 145-148 [PMID: 24973282 DOI: 10.1016/j.jcv.2014.05.014].
63. Morota K, Fujinami R, Kinukawa H, Machida T, Ohno K, Saegusa H, Takeda K. A new sensitive and automated chemiluminescent microparticle immunoassay for quantitative determination of hepatitis C virus core antigen. J Virol Methods 2009; 157: 8-14 [PMID: 19135481 DOI: 10.1016/j.jviromet.2008.12.009].
64. Fytili P, Tiemann C, Wang C, Schulz S, Schaffer S, Manns MP, Wedemeyer H. Frequency of very low HCV viremia detected by a highly sensitive HCV-RNA assay. J Clin Virol 2007; 39: 308-311 [PMID: 17625963 DOI: 10.1016/j.jcv.2007.05.007].
65. Laperche S, Le Marrec N, Girault A, Bouchardeau F, Servant-Delmas A, Maniez-Montreuil M, Gallian P, Levayer T, Morel P, Simon N. Simultaneous detection of hepatitis C virus (HCV) core antigen and anti-HCV antibodies improves the early detection of HCV infection. J Clin Microbiol 2005; 43: 3877-3883 [PMID: 16081925 DOI: 10.1128/JCM.43.8.3877-3883.2005].
66. Waldenström J, Konar J, Ekermo B, Norder H, Lagging M. Neonatal transfusion-transmitted hepatitis C virus infection following a pre-seroconversion window-phase donation in Sweden. Scand J Infect Dis 2013; 45: 796-799 [PMID: 23746339 DOI: 10.3109/00365548.2013.797601].
67. Vermehren J, Susser S, Berger A, Perner D, Peiffer KH, Allwinn R, Zeuzem S, Sarrazin C. Clinical utility of the ARCHITECT HCV Ag assay for early treatment monitoring in patients with chronic hepatitis C genotype 1 infection. J Clin Virol 2012; 55: 17-22 [PMID: 22698697 DOI: 10.1016/j.jcv.2012.05.008].
68. Coppola N, Pisapia R, Marrocco C, Martini S, Vatiero LM, Messina V, Tonziello G, Sagnelli C, Filippini P, Piccinino F, Sagnelli E. Anti-HCV IgG avidity index in acute hepatitis C. J Clin Virol 2007; 40: 110-115 [PMID: 17720621 DOI: 10.1016/j. jcv.2007.07.005].
69. Pawlotsky JM, Prescott L, Simmonds P, Pellet C, Laurent-Puig P, Labonne C, Darthuy F, Remire J, Duval J, Buffet C, Etienne JP, Dhumeaux D, Dussaix E. Serological determination of hepatitis C virus genotype: comparison with a standardized genotyping assay. J Clin Microbiol 1997; 35: 1734-1739 [PMID: 9196183].
70. Murphy DG, Willems B, Deschênes M, Hilzenrat N, Mousseau R, Sabbah S. 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 2007; 45: 1102-1112 [PMID: 17287328].
71. Lam TH, Cheng RS, Lai ST, Tsang TY, Cheng VC, Ho SL, Yam WC. Evaluation of in-house and commercial genotyping assays for molecular typing of hepatitis C virus in Hong Kong. Br J Biomed Sci 2010; 67: 82-85 [PMID: 20669764].
72. 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. Evaluation of Versant hepatitis C virus genotype assay (LiPA) 2.0. J Clin Microbiol 2008; 46: 1901-1906 [PMID: 18400913 DOI: 10.1128/JCM.02390-07].
73. Shinol RC, Gale HB, Kan VL. Performance of the Abbott RealTime HCV Genotype II RUO assay. J Clin Microbiol 2012; 50: 3099-3101 [PMID: 22760043 DOI: 10.1128/JCM.01249-12].
74. Chevaliez S, Bouvier-Alias M, Brillet R, Pawlotsky JM. Hepatitis C virus (HCV) genotype 1 subtype identification in new HCV drug development and future clinical practice. PLoS One 2009; 4: e8209 [PMID: 19997618 DOI: 10.1371/journal.pone.0008209].
75. Schneider MD, Sarrazin C. Antiviral therapy of hepatitis C in 2014: do we need resistance testing?. Antiviral Res 2014; 105: 64-71 [PMID: 24583028 DOI: 10.1016/j.antiviral.2014.02.011].
76. Erhardt A, Deterding K, Benhamou Y, Reiser M, Forns X, Pol S, Calleja JL, Ross S, Spangenberg HC, Garcia-Samaniego J, Fuchs M, Enríquez J, Wiegand J, Stern J, Wu K, Kukolj G, Marquis M, Beaulieu P, Nehmiz G, Steffgen J. Safety, pharmacokinetics and antiviral effect of BILB 1941, a novel hepatitis C virus RNA polymerase inhibitor, after 5 days oral treatment. Antivir Ther 2009; 14: 23-32 [PMID: 19320234].
77. Alter MJ. Epidemiology of hepatitis C virus infection. World J Gastroenterol 2007; 13: 2436-2441 [PMID: 17552026].
78. Seeff LB. Natural history of chronic hepatitis C. Hepatology 2002; 36: S35-S46 [PMID: 12407575 DOI: 10.1053/jhep.2002.36806].
79. Fattovich G, Giustina G, Degos F, Diodati G, Tremolada F, Nevens F, Almasio P, Solinas A, Brouwer JT, Thomas H, Realdi G, Corrocher R, Schalm SW. Effectiveness of interferon alfa on incidence of hepatocellular carcinoma and decompensation in cirrhosis type C. European Concerted Action on Viral Hepatitis (EUROHEP). J Hepatol 1997; 27: 201-205 [PMID: 9252096].
80. Toshikuni N, Arisawa T, Tsutsumi M. Hepatitis C-related liver cirrhosis-strategies for the prevention of hepatic decompensation, hepatocarcinogenesis, and mortality. World J Gastroenterol 2014; 20: 2876-2887 [PMID: 24659879 DOI: 10.3748/wjg.v20.i11.2876].
81. Swain MG, Lai MY, Shiffman ML, Cooksley WG, Zeuzem S, Dieterich DT, Abergel A, Pessôa MG, Lin A, Tietz A, Connell EV, Diago M. A sustained virologic response is durable in patients with chronic hepatitis C treated with peginterferon alfa-2a and ribavirin. Gastroenterology 2010; 139: 1593-1601 [PMID: 20637202 DOI: 10.1053/j.gastro.2010.07.009].
82. Backus LI, Boothroyd DB, Phillips BR, Belperio P, Halloran J, Mole LA. A sustained virologic response reduces risk of allcause mortality in patients with hepatitis C. Clin Gastroenterol Hepatol 2011; 9: 509-516.e1 [PMID: 21397729 DOI: 10.1016/j. cgh.2011.03.004].
83. Garg G, Kar P. Management of HCV infection: current issues and future options. Trop Gastroenterol 2009; 30: 11-18 [PMID: 19624082].
84. Au JS, Pockros PJ. Novel therapeutic approaches for hepatitis C. Clin Pharmacol Ther 2014; 95: 78-88 [PMID: 24126682 DOI: 10.1038/clpt.2013.206].
85. Pawlotsky JM. New hepatitis C virus (HCV) drugs and the hope for a cure: concepts in anti-HCV drug development. Semin Liver Dis 2014; 34: 22-29 [PMID: 24782255 DOI: 10.1055/s-0034-1371007].
86. Pawlotsky JM. New hepatitis C therapies. Semin Liver Dis 2014; 34: 7-8 [PMID: 24782253 DOI: 10.1055/s-0034-1371178].
87. Poordad F, McCone J, 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. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med 2011; 364: 1195-1206 [PMID: 21449783 DOI: 10.1056/NEJMoa1010494].
88. McHutchison JG, Everson GT, Gordon SC, Jacobson IM, Sulkowski M, Kauffman R, McNair L, Alam J, Muir AJ. Telaprevir with peginterferon and ribavirin for chronic HCV genotype 1 infection. N Engl J Med 2009; 360: 1827-1838 [PMID: 19403902 DOI: 10.1056/NEJMoa0806104].
89. Yee HS, Chang MF, Pocha C, Lim J, Ross D, Morgan TR, Monto A. Update on the management and treatment of hepatitis C virus infection: recommendations from the Department of Veterans Affairs Hepatitis C Resource Center Program and the National Hepatitis C Program Office. Am J Gastroenterol 2012; 107: 669-89; quiz 690 [PMID: 22525303 DOI: 10.1038/ajg.2012.48].
90. Gatselis NK, Zachou K, Saitis A, Samara M, Dalekos GN. Individualization of chronic hepatitis C treatment according to the host characteristics. World J Gastroenterol 2014; 20: 2839-2853 [PMID: 24659876 DOI: 10.3748/wjg.v20.i11.2839].
91. Zhu Y, Chen S. Antiviral treatment of hepatitis C virus infection and factors affecting efficacy. World J Gastroenterol 2013; 19: 8963-8973 [PMID: 24379621 DOI: 10.3748/wjg.v19.i47.8963].
92. Lawitz E, Poordad FF, Pang PS, Hyland RH, Ding X, Mo H, Symonds WT, McHutchison JG, Membreno FE. Sofosbuvir and ledipasvir fixed-dose combination with and without ribavirin in treatment-naive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR): an open-label, randomised, phase 2 trial. Lancet 2014; 383: 515-523 [PMID: 24209977 DOI: 10.1016/S0140-6736(13)62121-2].
93. Manns M, Pol S, Jacobson IM, Marcellin P, Gordon SC, Peng CY, Chang TT, Everson GT, Heo J, Gerken G, Yoffe B, Towner WJ, Bourliere M, Metivier S, Chu CJ, Sievert W, Bronowicki JP, Thabut D, Lee YJ, Kao JH, McPhee F, Kopit J, Mendez P, Linaberry M, Hughes E, Noviello S. All-oral daclatasvir plus asunaprevir for hepatitis C virus genotype 1b: a multinational, phase 3, multicohort study. Lancet 2014; 384: 1597-1605 [PMID: 25078304 DOI: 10.1016/S0140-6736(14)61059-X].
94. Gentile I, Buonomo AR, Borgia G. Dasabuvir: A Non-Nucleoside Inhibitor of NS5B for the Treatment of Hepatitis C Virus Infection. Rev Recent Clin Trials 2014; Epub ahead of print [PMID: 24882169].
95. Gentile I, Borgia F, Buonomo AR, Zappulo E, Castaldo G, Borgia G. ABT-450: a novel protease inhibitor for the treatment of hepatitis C virus infection. Curr Med Chem 2014; 21: 3261-3270 [PMID: 25005190].
96. Bichoupan K, Dieterich DT, Martel-Laferrière V. HIV-hepatitis C virus co-infection in the era of direct-acting antivirals. Curr HIV/AIDS Rep 2014; 11: 241-249 [PMID: 24996617 DOI: 10.1007/s1190 4-014-0217-9].
97. Keating GM. Sofosbuvir: a review of its use in patients with chronic hepatitis C. Drugs 2014; 74: 1127-1146 [PMID: 24958336 DOI: 10.1007/s40265-014-0247-z].
98. Gentile I, Buonomo AR, Borgia G. Ombitasvir: a potent pangenotypic inhibitor of NS5A for the treatment of hepatitis C virus infection. Expert Rev Anti Infect Ther 2014; 12: 1033-1043 [PMID: 25074011 DOI: 10.1586/14787210.2014.940898].
99. Gentile I, Buonomo AR, Zappulo E, Minei G, Morisco F, Borrelli F, Coppola N, Borgia G. Asunaprevir, a protease inhibitor for the treatment of hepatitis C infection. Ther Clin Risk Manag 2014; 10: 493-504 [PMID: 25061308 DOI: 10.2147/TCRM.S66731].
100. deLemos AS, Chung RT. Hepatitis C treatment: an incipient therapeutic revolution. Trends Mol Med 2014; 20: 315-321 [PMID: 24636306 DOI: 10.1016/j.molmed.2014.02.002].
101. Feld JJ. The beginning of the end: what is the future of interferon therapy for chronic hepatitis C?. Antiviral Res 2014; 105: 32-38 [PMID: 24548815 DOI: 10.1016/j.antiviral.2014.02.005].
102. Maini MK, Schurich A. Direct-acting antivirals trump interferonalpha in their capacity to rescue exhausted T cells upon HCV clearance. J Hepatol 2014; 61: 459-461 [PMID: 24953024 DOI: 10.1016/j.jhep.2014.06.017].
103. Manns MP, von Hahn T. Novel therapies for hepatitis C-one pill fits all?. Nat Rev Drug Discov 2013; 12: 595-610 [PMID: 23807378 DOI: 10.1038/nrd4050].
104. Bichoupan K, Martel-Laferriere V, Sachs D, Ng M, Schonfeld EA, Pappas A, Crismale J, Stivala A, Khaitova V, Gardenier D, Linderman M, Perumalswami PV, Schiano TD, Odin JA, Liu L, Moskowitz AJ, Dieterich DT, Branch AD. Costs of telaprevir-based triple therapy for hepatitis C: $189,000 per sustained virological response. Hepatology 2014; 60: 1187-1195 [PMID: 25065814 DOI: 10.1002/hep.27340].
105. Gurusamy KS, Wilson E, Koretz RL, Allen VB, Davidson BR, Burroughs AK, Gluud C. Is sustained virological response a marker of treatment efficacy in patients with chronic hepatitis C viral infection with no response or relapse to previous antiviral intervention?. PLoS One 2013; 8: e83313 [PMID: 24349487 DOI: 10.1371/journal.pone.0083313].
106. Brok J, Gluud LL, Gluud C. Ribavirin plus interferon versus interferon for chronic hepatitis C. Cochrane Database Syst Rev 2010; (1): CD005445 [PMID: 20091577 DOI: 10.1002/14651858. CD005445.pub2].
107. Hauser G, Awad T, Brok J, Thorlund K, Štimac D, Mabrouk M, Gluud C, Gluud LL. Peginterferon plus ribavirin versus interferon plus ribavirin for chronic hepatitis C. Cochrane Database Syst Rev 2014; 2: CD005441 [PMID: 24585509 DOI: 10.1002/14651858. CD005441.pub3].
108. Gluud C, Koretz R, Gurusamy K. Hepatitis C: a new direction, but an old story?. Lancet 2014; 383: 2122-2123 [PMID: 24953469 DOI: 10.1016/S0140-6736(14)61025-4].
109. Poveda E, Wyles DL, Mena A, Pedreira JD, Castro-Iglesias A, Cachay E. Update on hepatitis C virus resistance to directacting antiviral agents. Antiviral Res 2014; 108: 181-191 [PMID: 24911972].
110. Donaldson EF, Harrington PR, O'Rear JJ, Naeger LK. Clinical evidence and bioinformatics characterization of potential hepatitis C virus resistance pathways for sofosbuvir. Hepatology 2015; 61: 56-65 [PMID: 25123381 DOI: 10.1002/hep.27375].
111. Colombatto P, Brunetto MR, Maina AM, Romagnoli V, Almasio P, Rumi MG, Ascione A, Pinzello G, Mondelli M, Muratori L, Rappuoli R, Rosa D, Houghton M, Abrignani S, Bonino F. HCV E1E2-MF59 vaccine in chronic hepatitis C patients treated with PEG-IFNa2a and Ribavirin: a randomized controlled trial. J Viral Hepat 2014; 21: 458-465 [PMID: 24750327 DOI: 10.1111/jvh.12163].
112. Houghton M, Law JL, Tyrrell DL. An inactivated hepatitis C virus vaccine on the horizon?. Gastroenterology 2013; 145: 285-288 [PMID: 23806539 DOI: 10.1053/j.gastro.2013.06.029].
113. Law JL, Chen C, Wong J, Hockman D, Santer DM, Frey SE, Belshe RB, Wakita T, Bukh J, Jones CT, Rice CM, Abrignani S, Tyrrell DL, Houghton M. A hepatitis C virus (HCV) vaccine comprising envelope glycoproteins gpE1/gpE2 derived from a single isolate elicits broad cross-genotype neutralizing antibodies in humans. PLoS One 2013; 8: e59776 [PMID: 23527266 DOI: 10.1371/journal.pone.0059776].