Chapter 14 : Clinical Aspects of Hepatitis C Virus Infection

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Recently, the most significant progress in knowledge of hepatitis C virus (HCV) biology and interaction with host cells has concerned the role of lipids for genome replication, assembly and egress, and entry into cells. The major hepatic consequence of HCV infection is the progression to cirrhosis and its complications, such as ascites, hepatic insufficiency, and hepatocellular carcinoma (HCC). With the identification in 1989 of HCV as the infectious agent responsible for non-A/non-B hepatitis and the development of specific detection tests, it has become possible to monitor the efficacy of interferon (IFN)-α treatment. With the increased survival associated with the use of highly active antiretroviral therapy (HAART), morbidity and mortality from HCV-induced liver disease have started to increase significantly. Microarray results from liver biopsy tissue taken before therapy in a cohort of patients given pegIFN and ribavirin were recently reported. In this study, patients who were subsequently identified as non-responders had high baseline expression of IFN-stimulated genes (ISGs), whereas responders to therapy more closely resembled healthy controls. Kempf et al. illustrated the need for good knowledge of drug metabolism to improve the efficacy of a drug in vivo. In this study it was shown that a pharmacokinetic enhancement of telaprevir and boceprevir could be achieved by codosing with ritonavir, a potent inhibitor of the cytochrome P450 3A, which is involved in the metabolism of both drugs.

Citation: Durantel D, Zoulim F. 2009. Clinical Aspects of Hepatitis C Virus Infection, p 241-264. In LaFemina, Ph. D. R (ed), Antiviral Research. ASM Press, Washington, DC. doi: 10.1128/9781555815493.ch14
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Image of Figure 1.
Figure 1.

Natural history of hepatitis C infection.

Citation: Durantel D, Zoulim F. 2009. Clinical Aspects of Hepatitis C Virus Infection, p 241-264. In LaFemina, Ph. D. R (ed), Antiviral Research. ASM Press, Washington, DC. doi: 10.1128/9781555815493.ch14
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Image of Figure 2.
Figure 2.

Evolution of SVR with different therapies during the past decade.

Citation: Durantel D, Zoulim F. 2009. Clinical Aspects of Hepatitis C Virus Infection, p 241-264. In LaFemina, Ph. D. R (ed), Antiviral Research. ASM Press, Washington, DC. doi: 10.1128/9781555815493.ch14
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Image of Figure 3.
Figure 3.

The main types of treatment response in chronic hepatitis C. (A) SVR; (B) virologic response followed by a relapse; (C) virologic nonresponse.

Citation: Durantel D, Zoulim F. 2009. Clinical Aspects of Hepatitis C Virus Infection, p 241-264. In LaFemina, Ph. D. R (ed), Antiviral Research. ASM Press, Washington, DC. doi: 10.1128/9781555815493.ch14
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Image of Figure 4.
Figure 4.

SVR in phase III trials of pegIFN-α2a with and without ribavirin (RBV) (A) or pegIFN-α2b with or without ribavirin (B).

Citation: Durantel D, Zoulim F. 2009. Clinical Aspects of Hepatitis C Virus Infection, p 241-264. In LaFemina, Ph. D. R (ed), Antiviral Research. ASM Press, Washington, DC. doi: 10.1128/9781555815493.ch14
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Image of Figure 5.
Figure 5.

Importance of monitoring early virologic response during treatment of genotype 1 infection patients with respect to outcome. W, week.

Citation: Durantel D, Zoulim F. 2009. Clinical Aspects of Hepatitis C Virus Infection, p 241-264. In LaFemina, Ph. D. R (ed), Antiviral Research. ASM Press, Washington, DC. doi: 10.1128/9781555815493.ch14
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Figure 6.

SVR rates following treatment with pegIFN-α and ribavirin in difficult-to-treat populations.

Citation: Durantel D, Zoulim F. 2009. Clinical Aspects of Hepatitis C Virus Infection, p 241-264. In LaFemina, Ph. D. R (ed), Antiviral Research. ASM Press, Washington, DC. doi: 10.1128/9781555815493.ch14
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Figure 7.

Future concept of anti-HCV therapy. DMPK, drug metabolism and pharmacokinetic profile.

Citation: Durantel D, Zoulim F. 2009. Clinical Aspects of Hepatitis C Virus Infection, p 241-264. In LaFemina, Ph. D. R (ed), Antiviral Research. ASM Press, Washington, DC. doi: 10.1128/9781555815493.ch14
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1. Asselah, T.,, L. Rubbia-Brandt,, P. Marcellin, and, F. Negro. 2006. Steatosis in chronic hepatitis C: why does it really matter? Gut 55: 123130.
2. Bain, V. G.,, E. M. Yoshida,, K. D. Kaita,, M. G. Swain,, E. J. Heath-cote,, A. Garcia,, P. A. Moore,, R. Yu,, J. G. McHutchison, and, G. M. Subramanian. 2006. Dynamics of interferon-specific gene expression in peripheral blood of interferon alfa-naive patients with genotype 1 chronic hepatitis C infection treated with albumininterferon alfa. Hepatol. Res. 35: 256262.
3. Bartenschlager, R. 2002. In vitro models for hepatitis C. Virus Res. 82: 2532.
4. Basso, M.,, F. Torre,, A. Grasso,, G. Percario,, E. Azzola,, S. Artioli,, S. Blanchi,, N. Pelli, and, A. Picciotto. 2007. Pegylated interferon and ribavirin in re-treatment of responder-relapser HCV patients. Dig. Liver Dis. 39: 4751.
5. Berenguer, M.,, A. Palau,, A. Fernandez,, S. Benlloch,, V. Aguilera,, M. Prieto,, J. M. Rayon, and, J. Berenguer. 2006. Efficacy, predictors of response, and potential risks associated with antiviral therapy in liver transplant recipients with recurrent hepatitis C. Liver Transpl. 12: 10671076.
6. Berg, C.,, F. L. Goncales, Jr.,, D. E. Bernstein,, H. Sette, Jr.,, J. Rasenack,, M. Diago,, D. M. Jensen,, P. Graham, and, G. Cooksley. 2006. Re-treatment of chronic hepatitis C patients after relapse: efficacy of peginterferon-alpha-2a (40 kDa) and ribavirin. J. Viral Hepat. 13: 435440.
7. Berg, T.,, M. von Wagner,, S. Nasser,, C. Sarrazin,, T. Heintges,, T. Gerlach,, P. Buggisch,, T. Goeser,, J. Rasenack,, G. R. Pape,, W. E. Schmidt,, B. Kallinowski,, H. Klinker,, U. Spengler,, P. Martus,, U. Alshuth, and, S. Zeuzem. 2006. Extended treatment duration for hepatitis C virus type 1: comparing 48 versus 72 weeks of peginterferon-alfa-2a plus ribavirin. Gastroenterology 130: 10861097.
8. Biggins, S. W., and, N. A. Terrault. 2006. Management of recurrent hepatitis C in liver transplant recipients. Infect. Dis. Clin. N. Am. 20: 155174.
9. Biggins, S. W., and, N. A. Terrault. 2005. Treatment of recurrent hepatitis C after liver transplantation. Clin. Liver Dis. 9: 505523.
10. Bizollon, T.,, P. Pradat,, J. Y. Mabrut,, M. Chevallier,, M. Adham,, S. Radenne,, J. C. Souquet,, C. Ducerf,, J. Baulieux,, F. Zoulim, and, C. Trepo. 2005. Benefit of sustained virological response to combination therapy on graft survival of liver transplanted patients with recurrent chronic hepatitis C. Am. J. Transplant. 5: 19091913.
11. Blackard, J. T.,, N. Kemmer, and, K. E. Sherman. 2006. Extrahepatic replication of HCV: insights into clinical manifestations and biological consequences. Hepatology 44: 1522.
12. Bouchardeau, F.,, J. F. Cantaloube,, S. Chevaliez,, C. Portal,, A. Razer,, J. J. Lefrere,, J. M. Pawlotsky,, P. De Micco, and, S. Laperche. 2007. Improvement of hepatitis C virus (HCV) genotype determination with the new version of the INNO-LiPA HCV assay. J. Clin. Microbiol. 45: 11401145.
13. Breiman, A.,, N. Grandvaux,, R. Lin,, C. Ottone,, S. Akira,, M. Yoneyama,, T. Fujita,, J. Hiscott, and, E. F. Meurs. 2005. Inhibition of RIG-I-dependent signaling to the interferon pathway during hepatitis C virus expression and restoration of signaling by IKKepsilon. J. Virol. 79: 39693978.
14. Broers, B.,, B. Helbling,, A. Francois,, P. Schmid,, C. Chuard,, A. Hadengue, and, F. Negro. 2005. Barriers to interferon-alpha therapy are higher in intravenous drug users than in other patients with acute hepatitis C. J. Hepatol. 42: 323328.
15. Cacoub, P.,, D. Saadoun,, N. Limal,, J. M. Leger, and, T. Maisonobe. 2005. Hepatitis C virus infection and mixed cryoglobulinaemia vasculitis: a review of neurological complications. AIDS 19(Suppl. 3): S128S134.
16. Cacoub, P.,, D. Saadoun,, N. Limal,, D. Sene,, O. Lidove, and, J. C. Piette. 2005. PEGylated interferon alfa-2b and ribavirin treatment in patients with hepatitis C virus-related systemic vasculitis. Arthritis Rheum. 52: 911915.
17. Carrat, F.,, F. Bani-Sadr,, S. Pol,, E. Rosenthal,, F. Lunel-Fabiani,, A. Benzekri,, P. Morand,, C. Goujard,, G. Pialoux,, L. Piroth,, D. Salmon-Ceron,, C. Degott,, P. Cacoub, and, C. Perronne. 2004. Pegylated interferon alfa-2b vs standard interferon alfa-2b, plus ribavirin, for chronic hepatitis C in HIV-infected patients: a randomized controlled trial. JAMA 292: 28392848.
18. Castera, L. 2006. Steatosis, insulin resistance and fibrosis progression in chronic hepatitis C. Minerva Gastroenterol. Dietol. 52: 125134.
19. Chen, L.,, I. Borozan,, J. Feld,, J. Sun,, L. L. Tannis,, C. Coltescu,, J. Heathcote,, A. M. Edwards, and, I. D. McGilvray. 2005. Hepatic gene expression discriminates responders and nonresponders in treatment of chronic hepatitis C viral infection. Gastroenterology 128: 14371444.
20. Chevaliez, S.,, M. Bouvier-Alias,, R. Brillet, and, J. M. Pawlotsky. 2007. Overestimation and underestimation of hepatitis C virus RNA levels in a widely used real-time polymerase chain reaction-based method. Hepatology 46: 2231.
21. Chevaliez, S.,, R. Brillet,, E. Lazaro,, C. Hezode, and, J. M. Pawlotsky. 2007. Analysis of ribavirin mutagenicity in human hepatitis C virus infection. J. Virol. 81: 77327741.
22. Chevaliez, S., and, J. M. Pawlotsky. 2005. Use of virologic assays in the diagnosis and management of hepatitis C virus infection. Clin. Liver Dis. 9: 371382.
23. Chisari, F. V. 2005. Unscrambling hepatitis C virus-host interactions. Nature 436: 930932.
24. Choo, Q.,, G. Kuo,, A. Weiner,, L. Overby,, D. Bradley, and, M. Houghton. 1989. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science 244: 359362.
25. Christen, V.,, S. Treves,, F. H. Duong, and, M. H. Heim. 2007. Activation of endoplasmic reticulum stress response by hepatitis viruses up-regulates protein phosphatase 2A. Hepatology 46: 558565.
26. Coelmont, L.,, J. Paeshuyse,, M. P. Windisch,, E. De Clercq,, R. Bartenschlager, and, J. Neyts. 2006. Ribavirin antagonizes the in vitro anti-hepatitis C virus activity of 2´-C-methylcytidine, the active component of valopicitabine. Antimicrob. Agents Che-mother. 50: 34443446.
27. Comanor, L.,, C. Elkin,, K. Leung,, M. Krajden,, K. Kronquist,, K. Nicolas,, E. Horansky,, M. deMedina,, P. Kittichai,, E. Sablon,, R. Ziermann, and, C. Sherlock. 2003. Successful HCV genotyping of previously failed and low viral load specimens using an HCV RNA qualitative assay based on transcription-mediated amplification in conjunction with the line probe assay. J. Clin. Virol. 28: 1426.
28. Conjeevaram, H. S.,, M. W. Fried,, L. J. Jeffers,, N. A. Terrault,, T. E. Wiley-Lucas,, N. Afdhal,, R. S. Brown,, S. H. Belle,, J. H. Hoofnagle,, D. E. Kleiner, and, C. D. Howell. 2006. Peginterferon and ribavirin treatment in African American and Caucasian American patients with hepatitis C genotype 1. Gastroenterology 131: 470477.
29. Contreras, A. M.,, Y. Hiasa,, W. He,, A. Terella,, E. V. Schmidt, and, R. T. Chung. 2002. Viral RNA mutations are region specific and increased by ribavirin in a full-length hepatitis C virus replication system. J. Virol. 76: 85058517.
30. Crotty, S.,, C. E. Cameron, and, R. Andino. 2001. RNA virus error catastrophe: direct molecular test by using ribavirin. Proc. Natl. Acad. Sci. USA 98: 68956900.
31. Crotty, S.,, D. Maag,, J. J. Arnold,, W. Zhong,, J. Y. Lau,, Z. Hong,, R. Andino, and, C. E. Cameron. 2000. The broad-spectrum antiviral ribonucleoside ribavirin is an RNA virus mutagen. Nat. Med. 6: 13751379.
32. Davis, G. L. 1999. Combination therapy with interferon alfa and ribavirin as retreatment of interferon relapse in chronic hepatitis C. Semin. Liver Dis. 19(Suppl. 1): 4955.
33. Davis, G. L. 2002. Monitoring of viral levels during therapy of hepatitis C. Hepatology 36: S145S151.
34. De Francesco, R., and, G. Migliaccio. 2005. Challenges and successes in developing new therapies for hepatitis C. Nature 436: 953960.
35. Di Bisceglie, A. M.,, H. S. Conjeevaram,, M. W. Fried,, R. Sallie,, Y. Park,, C. Yurdaydin,, M. Swain,, D. E. Kleiner,, K. Mahaney, and, J. H. Hoofnagle. 1995. Ribavirin as therapy for chronic hepatitis C. A randomized, double-blind, placebo-controlled trial. Ann. Intern. Med. 123: 897903.
36. Di Bisceglie, A. M., and, J. H. Hoofnagle. 2002. Optimal therapy of hepatitis C. Hepatology 36: S121S127.
37. Di Bisceglie, A. M.,, J. McHutchison, and, C. M. Rice. 2002. New therapeutic strategies for hepatitis C. Hepatology 35: 224231.
38. Duong, F. H.,, V. Christen,, J. M. Berke,, S. H. Penna,, D. Morad-pour, and, M. H. Heim. 2005. Upregulation of protein phosphatase 2Ac by hepatitis C virus modulates NS3 helicase activity through inhibition of protein arginine methyltransferase 1. J. Virol. 79: 1534215350.
39. Duong, F. H.,, M. Filipowicz,, M. Tripodi,, N. La Monica, and, M. H. Heim. 2004. Hepatitis C virus inhibits interferon signaling through up-regulation of protein phosphatase 2A. Gastroenterology 126: 263277.
40. Durantel, D.,, V. Escuret, and, F. Zoulim. 2003. Current and emerging therapeutic approaches to hepatitis C infection. Expert. Rev. Anti-Infect. Ther. 1: 441454.
41. Durantel, D., and, F. Zoulim. 2007. Learning from HIV: how will drug resistance influence treatment strategies against hepatitis C? J. HIV Ther. 12: 8891.
42. Eckels, D. D.,, H. Wang,, T. H. Bian,, N. Tabatabai, and, J. C. Gill. 2000. Immunobiology of hepatitis C virus (HCV) infection: the role of CD4 T cells in HCV infection. Immunol. Rev. 174: 9097.
43. Egger, D.,, B. Wolk,, R. Gosert,, L. Bianchi,, H. E. Blum,, D. Morad-pour, and, K. Bienz. 2002. Expression of hepatitis C virus proteins induces distinct membrane alterations including a candidate viral replication complex. J. Virol. 76: 59745984.
44. Enomoto, N.,, I. Sakuma,, Y. Asahina,, M. Kurosaki,, T. Murakami,, C. Yamamoto,, N. Izumi,, F. Marumo, and, C. Sato. 1995. Comparison of full-length sequences of interferon-sensitive and resistant hepatitis C virus 1b. Sensitivity to interferon is conferred by amino acid substitutions in the NS5A region. J. Clin. Investig. 96: 224230.
45. Enomoto, N.,, I. Sakuma,, Y. Asahina,, M. Kurosaki,, T. Murakami,, C. Yamamoto,, Y. Ogura,, N. Izumi,, F. Marumo, and, C. Sato. 1996. Mutations in the nonstructural protein 5A gene and response to interferon in patients with chronic hepatitis C virus 1b infection. N. Engl. J. Med. 334: 7781.
46. Erdtmann, L.,, N. Franck,, H. Lerat,, J. Le Seyec,, D. Gilot,, I. Cannie,, P. Gripon,, U. Hibner, and, C. Guguen-Guillouzo. 2003. The hepatitis C virus NS2 protein is an inhibitor of CIDE-B-induced apoptosis. J. Biol. Chem. 278: 1825618264.
47. Escuret, V.,, A. Martin,, D. Durantel,, R. Parent,, O. Hantz,, C. Trepo,, T. Menguy,, E. Bottius,, J. Dardy,, J. Maral,, J. L. Escary, and, F. Zoulim. 2006. Novel alpha interferon (IFN-alpha) variant with improved inhibitory activity against hepatitis C virus genotype 1 replication compared to IFN-alpha2b therapy in a subgenomic replicon system. Antimicrob. Agents Chemother. 50: 39843991.
48. Everson, G. T. 2005. Treatment of hepatitis C in patients who have decompensated cirrhosis. Clin. Liver Dis. 9: 473486, viii.
49. Everson, G. T.,, J. Trotter,, L. Forman,, M. Kugelmas,, A. Halprin,, B. Fey, and, C. Ray. 2005. Treatment of advanced hepatitis C with a low accelerating dosage regimen of antiviral therapy. Hepatology 42: 255262.
50. Feld, J. J., and, J. H. Hoofnagle. 2005. Mechanism of action of interferon and ribavirin in treatment of hepatitis C. Nature 436: 967972.
51. Flexner, C. 2007. HIV drug development: the next 25 years. Nat. Rev. Drug Discov. 69596966.
52. Forns, X., and, J. Costa. 2006. HCV virological assessment. J. Hepatol. 44: S35S39.
53. Foy, E.,, K. Li,, R. Sumpter, Jr.,, Y. M. Loo,, C. L. Johnson,, C. Wang,, P. M. Fish,, M. Yoneyama,, T. Fujita,, S. M. Lemon, and, M. Gale, Jr. 2005. Control of antiviral defenses through hepatitis C virus disruption of retinoic acid-inducible gene-I signaling. Proc. Natl. Acad. Sci. USA 102: 29862991.
54. Foy, E.,, K. Li,, C. Wang,, R. Sumpter, Jr.,, M. Ikeda,, S. M. Lemon, and, M. Gale, Jr. 2003. Regulation of interferon regulatory factor-3 by the hepatitis C virus serine protease. Science 300: 11451148.
55. Fried, M. W.,, M. L. Shiffman,, K. R. Reddy,, C. Smith,, G. Marinos,, F. L. Goncales, Jr.,, D. Haussinger,, M. Diago,, G. Carosi,, D. Dhumeaux,, A. Craxi,, A. Lin,, J. Hoffman, and, J. Yu. 2002. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N. Engl. J. Med. 347: 975982.
56. Gale, M., Jr. 2003. Effector genes of interferon action against hepatitis C virus. Hepatology 37: 975978.
57. Gale, M., Jr.,, C. M. Blakely,, B. Kwieciszewski,, S. L. Tan,, M. Dossett,, N. M. Tang,, M. J. Korth,, S. J. Polyak,, D. R. Gretch, and, M. G. Katze. 1998. Control of PKR protein kinase by hepatitis C virus nonstructural 5A protein: molecular mechanisms of kinase regulation. Mol. Cell. Biol. 18: 52085218.
58. Gale, M., Jr., and, E. M. Foy. 2005. Evasion of intracellular host defence by hepatitis C virus. Nature 436: 939945.
59. Gale, M. J., Jr.,, M. J. Korth,, N. M. Tang,, S. L. Tan,, D. A. Hopkins,, T. E. Dever,, S. J. Polyak,, D. R. Gretch, and, M. G. Katze. 1997. Evidence that hepatitis C virus resistance to interferon is mediated through repression of the PKR protein kinase by the nonstructural 5A protein. Virology 230: 217227.
60. Geretti, A. M. 2006. Antiretroviral resistance. J. HIV Ther. 11: 7273.
61. Gilmour, K. C., and, N. C. Reich. 1995. Signal transduction and activation of gene transcription by interferons. Gene Expr. 5: 118.
62. Glue, P.,, R. Rouzier-Panis,, C. Raffanel,, R. Sabo,, S. K. Gupta,, M. Salfi,, S. Jacobs,, R. P. Clement, et al. 2000. A dose-ranging study of pegylated interferon alfa-2b and ribavirin in chronic hepatitis C. Hepatology 32: 647653.
63. Guo, J. T.,, V. V. Bichko, and, C. Seeger. 2001. Effect of alpha inter-feron on the hepatitis C virus replicon. J. Virol. 75: 85168523.
64. Guo, J. T.,, J. A. Sohn,, Q. Zhu, and, C. Seeger. 2004. Mechanism of the interferon alpha response against hepatitis C virus replicons. Virology 325: 7181.
65. Guo, J. T.,, Q. Zhu, and, C. Seeger. 2003. Cytopathic and noncytopathic interferon responses in cells expressing hepatitis C virus subgenomic replicons. J. Virol. 77: 1076910779.
66. Gupte, P.,, A. Dudhade, and, H. G. Desai. 2006. Acquired apolipo-protein B deficiency with chronic hepatitis C virus infection. Indian J. Gastroenterol. 25: 311312.
67. Hadziyannis, S. J.,, H. Sette, Jr.,, T. R. Morgan,, V. Balan,, M. Diago,, P. Marcellin,, G. Ramadori,, H. Bodenheimer, Jr.,, D. Bernstein,, M. Rizzetto,, S. Zeuzem,, P. J. Pockros,, A. Lin, and, A. M. Ackrill. 2004. Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann. Intern. Med. 140: 346355.
68. Halfon, P.,, M. Bourliere,, G. Penaranda,, H. Khiri, and, D. Ouzan. 2006. Real-time PCR assays for hepatitis C virus (HCV) RNA quantitation are adequate for clinical management of patients with chronic HCV infection. J. Clin. Microbiol. 44: 25072511.
69. Halfon, P.,, G. Penaranda,, M. Bourliere,, H. Khiri,, M. F. Masseyeff, and, D. Ouzan. 2006. Assessment of early virological response to antiviral therapy by comparing four assays for HCV RNA quantitation using the international unit standard: implications for clinical management of patients with chronic hepatitis C virus infection. J. Med. Virol. 78: 208215.
70. Heathcote, E. J.,, M. L. Shiffman,, W. G. Cooksley,, G. M. Dusheiko,, S. S. Lee,, L. Balart,, R. Reindollar,, R. K. Reddy,, T. L. Wright,, A. Lin,, J. Hoffman, and, J. De Pamphilis. 2000. Peginterferon alfa-2a in patients with chronic hepatitis C and cirrhosis. N. Engl. J. Med. 343: 16731680.
71. Heim, M. H.,, D. Moradpour, and, H. E. Blum. 1999. Expression of hepatitis C virus proteins inhibits signal transduction through the Jak-STAT pathway. J. Virol. 73: 84698475.
72. Hofmann, W. P.,, A. Polta,, E. Herrmann,, U. Mihm,, B. Kronenberger,, T. Sonntag,, V. Lohmann,, B. Schonberger,, S. Zeuzem, and, C. Sarrazin. 2007. Mutagenic effect of ribavirin on hepatitis C nonstructural 5B quasispecies in vitro and during antiviral therapy. Gastroenterology 132: 921930.
73. Hofmann, W. P.,, S. Zeuzem, and, C. Sarrazin. 2005. Hepatitis C virus-related resistance mechanisms to interferon alpha-based antiviral therapy. J. Clin. Virol. 32: 8691.
74. Hoofnagle, J. H.,, D. Lau,, H. Conjeevaram,, D. Kleiner, and, A. M. Di Bisceglie. 1996. Prolonged therapy of chronic hepatitis C with ribavirin. J. Viral Hepat. 3: 247252.
75. Hoofnagle, J. H.,, K. D. Mullen,, D. B. Jones,, V. Rustgi,, A. Di Bisceglie,, M. Peters,, J. G. Waggoner,, Y. Park, and, E. A. Jones. 1986. Treatment of chronic non-A, non-B hepatitis with recombinant human alpha interferon. A preliminary report. N. Engl. J. Med. 315: 15751578.
76. Houglum, K.,, A. Venkataramani,, K. Lyche, and, M. Chojkier. 1997. A pilot study of the effects of d-alpha-tocopherol on hepatic stellate cell activation in chronic hepatitis C. Gastroenterology 113: 10691073.
77. Huang, H.,, F. Sun,, D. M. Owen,, W. Li,, Y. Chen,, M. Gale, Jr., and, J. Ye. 2007. Hepatitis C virus production by human hepatocytes dependent on assembly and secretion of very low-density lipoproteins. Proc. Natl. Acad. Sci. USA 104: 58485853.
78. Jaeckel, E.,, M. Cornberg,, H. Wedemeyer,, T. Santantonio,, J. Mayer,, M. Zankel,, G. Pastore,, M. Dietrich,, C. Trautwein, and, M. P. Manns. 2001. Treatment of acute hepatitis C with interferon alfa-2b. N. Engl. J. Med. 345: 14521457.
79. Jeffers, L. J.,, W. Cassidy,, C. D. Howell,, S. Hu, and, K. R. Reddy. 2004. Peginterferon alfa-2a (40 kd) and ribavirin for black American patients with chronic HCV genotype 1. Hepatology 39: 17021708.
80. Johnson, R. J.,, D. R. Gretch,, H. Yamabe,, J. Hart,, C. E. Bacchi,, P. Hartwell,, W. G. Couser,, L. Corey,, M. H. Wener,, C. E. Alpers, et al. 1993. Membranoproliferative glomerulonephritis associated with hepatitis C virus infection. N. Engl. J. Med. 328: 465470.
81. Johnson, V. A.,, F. Brun-Vezinet,, B. Clotet,, B. Conway,, D. R. Kuritzkes,, D. Pillay,, J. Schapiro,, A. Telenti, and, D. Richman. 2005. Update of the drug resistance mutations in HIV-1: 2005. Top. HIV Med. 13: 5157.
82. Kamal, S. M.,, J. Fehr,, B. Roesler,, T. Peters, and, J. W. Rasenack. 2002. Peginterferon alone or with ribavirin enhances HCV-specific CD4 T-helper 1 responses in patients with chronic hepatitis C. Gastroenterology 123: 10701083.
83. Kamal, S. M.,, A. Ismail,, C. S. Graham,, Q. He,, J. W. Rasenack,, T. Peters,, A. A. Tawil,, J. J. Fehr,, S. Khalifa Kel,, M. M. Madwar, and, M. J. Koziel. 2004. Pegylated interferon alpha therapy in acute hepatitis C: relation to hepatitis C virus-specific T cell response kinetics. Hepatology 39: 17211731.
84. Kempf, D. J.,, C. Klein,, H. J. Chen,, L. L. Klein,, C. Yeung,, J. T. Randolph,, Y. Y. Lau,, L. E. Chovan,, Z. Guan,, L. Hernandez,, T. M. Turner,, P. J. Dandliker, and, K. C. Marsh. 2007. Pharmacokinetic enhancement of the hepatitis C virus protease inhibitors VX-950 and SCH 503034 by co-dosing with ritonavir. Antivir. Chem. Chemother. 18: 163167.
85. Koev, G.,, T. Dekhtyar,, L. Han,, P. Yan,, T. I. Ng,, C. T. Lin,, H. Mo, and, A. Molla. 2007. Antiviral interactions of an HCV polymerase inhibitor with an HCV protease inhibitor or inter-feron in vitro. Antivir. Res. 73: 7883.
86. Lanford, R. E.,, D. Chavez,, B. Guerra,, J. Y. Lau,, Z. Hong,, K. M. Brasky, and, B. Beames. 2001. Ribavirin induces error-prone replication of GB virus B in primary tamarin hepatocytes. J. Virol. 75: 80748081.
87. Lau, D. T.,, D. E. Kleiner,, M. G. Ghany,, Y. Park,, P. Schmid, and, J. H. Hoofnagle. 1998. 10-Year follow-up after interferon-alpha therapy for chronic hepatitis C. Hepatology 28: 11211127.
88. Lau, J. Y.,, R. C. Tam,, T. J. Liang, and, Z. Hong. 2002. Mechanism of action of ribavirin in the combination treatment of chronic HCV infection. Hepatology 35: 10021009.
89. Leeson, P. D., and, B. Springthorpe. 2007. The influence of drug-like concepts on decision-making in medicinal chemistry. Nat. Rev. Drug Discov. 6: 881890.
90. Levrero, M. 2006. Viral hepatitis and liver cancer: the case of hepatitis C. Oncogene 25: 38343847.
91. Liang, T. J., and, T. Heller. 2004. Pathogenesis of hepatitis C-associated hepatocellular carcinoma. Gastroenterology 127: S62S71.
92. Lin, C.,, C. A. Gates,, B. G. Rao,, D. L. Brennan,, J. R. Fulghum,, Y. P. Luong,, J. D. Frantz,, K. Lin,, S. Ma,, Y. Y. Wei,, R. B. Perni, and, A. D. Kwong. 2005. In vitro studies of cross-resistance mutations against two hepatitis C virus serine protease inhibitors, VX-950 and BILN 2061. J. Biol. Chem. 280: 3678436791.
93. Lin, C.,, K. Lin,, Y. P. Luong,, B. G. Rao,, Y. Y. Wei,, D. L. Brennan,, J. R. Fulghum,, H. M. Hsiao,, S. Ma,, J. P. Maxwell,, K. M. Cottrell,, R. B. Perni,, C. A. Gates, and, A. D. Kwong. 2004. In vitro resistance studies of hepatitis C virus serine protease inhibitors, VX-950 and BILN 2061: structural analysis indicates different resistance mechanisms. J. Biol. Chem. 279: 1750817514.
94. Lindenbach, B. D., and, C. M. Rice. 2005. Unravelling hepatitis C virus replication from genome to function. Nature 436: 933938.
95. Lindh, M., and, C. Hannoun. 2005. Genotyping of hepatitis C virus by Taqman real-time PCR. J. Clin. Virol. 34: 108114.
96. Lindsay, K. L.,, C. Trepo,, T. Heintges,, M. L. Shiffman,, S. C. Gordon,, J. C. Hoefs,, E. R. Schiff,, Z. D. Goodman,, M. Laughlin,, R. Yao, and, J. K. Albrecht. 2001. A randomized, double-blind trial comparing pegylated interferon alfa-2b to interferon alfa-2b as initial treatment for chronic hepatitis C. Hepatology 34: 395403.
97. Lok, A. S.,, F. Zoulim,, S. Locarnini,, A. Bartholomeusz,, M. G. Ghany,, J. M. Pawlotsky,, Y. F. Liaw,, M. Mizokami, and, C. Kuiken. 2007. Antiviral drug-resistant HBV: standardization of nomenclature and assays and recommendations for management. Hepatology 46: 254265.
98. Lonardo, A.,, L. E. Adinolfi,, P. Loria,, N. Carulli,, G. Ruggiero, and, C. P. Day. 2004. Steatosis and hepatitis C virus: mechanisms and significance for hepatic and extrahepatic disease. Gastroenterology 126: 586597.
99. Maag, D.,, C. Castro,, Z. Hong, and, C. E. Cameron. 2001. Hepatitis C virus RNA-dependent RNA polymerase (NS5B) as a mediator of the antiviral activity of ribavirin. J. Biol. Chem. 276: 4609446098.
100. Manns, M. P.,, J. G. McHutchison,, S. C. Gordon,, V. K. Rustgi,, M. Shiffman,, R. Reindollar,, Z. D. Goodman,, K. Koury,, M. Ling, and, J. K. Albrecht. 2001. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 358: 958965.
101. Marcellin, P.,, M. Bourliere,, J. M. Pawlotsky, and, D. Ouzan. 2007. HCV non-responder patients: definition of non-response and treatment strategy. Gastroenterol. Clin. Biol. 31:4S 134S19. (In French.)
102. Martro, E.,, V. Gonzalez,, A. J. Buckton,, V. Saludes,, G. Fernandez,, L. Matas,, R. Planas, and, V. Ausina. 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. Micro-biol. 46: 192197.
103. McHutchison, J. G.,, G. Dusheiko,, M. L. Shiffman,, M. Rodriguez-Torres,, S. Sigal,, M. Bourliere,, T. Berg,, S. C. Gordon,, F. M. Campbell,, D. Theodore,, N. Blackman,, J. Jenkins, and, N. H. Afdhal. 2007. Eltrombopag for thrombocytopenia in patients with cirrhosis associated with hepatitis C. N. Engl. J. Med. 357: 22272236.
104. McHutchison, J. G.,, G. T. Everson,, S. C. Gordon,, I. Jacobson,, R. Kauffman,, L. McNair, and, A. J. Muir. 2008. Prove 1: results from a phase 2 study of telaprevir with peg-interferon alfa-2A and ribavirin in treatment-naive subjects with hepatitis C. J. Hepatol. 48:S4.
105. McHutchison, J. G., and, T. Poynard. 1999. Combination therapy with interferon plus ribavirin for the initial treatment of chronic hepatitis C. Semin. Liver Dis. 19(Suppl. 1): 5765.
106. Misiani, R.,, P. Bellavita,, D. Fenili,, O. Vicari,, D. Marchesi,, P. L. Sironi,, P. Zilio,, A. Vernocchi,, M. Massazza,, G. Vendramin, et al. 1994. Interferon alfa-2a therapy in cryoglobulinemia associated with hepatitis C virus. N. Engl. J. Med. 330: 751756.
107. Mo, H.,, L. Lu,, T. Pilot-Matias,, R. Pithawalla,, R. Mondal,, S. Masse,, T. Dekhtyar,, T. Ng,, G. Koev,, V. Stoll,, K. D. Stewart,, J. Pratt,, P. Donner,, T. Rockway,, C. Maring, and, A. Molla. 2005. Mutations conferring resistance to a hepatitis C virus (HCV) RNA-dependent RNA polymerase inhibitor alone or in combination with an HCV serine protease inhibitor in vitro. Antimicrob. Agents Chemother. 49: 43054314.
108. Muir, A. J.,, J. D. Bornstein, and, P. G. Killenberg. 2004. Peginterferon alfa-2b and ribavirin for the treatment of chronic hepatitis C in blacks and non-Hispanic whites. N. Engl. J. Med. 350: 22652271.
109. Nadarajah, R.,, G. Y. Khan,, S. A. Miller, and, G. F. Brooks. 2007. Evaluation of a new-generation line-probe assay that detects 5´ untranslated and core regions to genotype and subtype hepatitis C virus. Am. J. Clin. Pathol. 128: 300304.
110. Nagaki, M.,, M. Imose,, T. Naiki,, K. Kimura,, H. Hayashi,, M. Shimizu,, H. Ohnishi,, E. Tomita,, J. Sugihara,, K. Amano,, T. Sakai,, T. Kojima,, N. Katsumura,, Y. Kondo,, M. Fujimoto, and, H. Moriwaki. 2005. Prospective study on early virologic response to treatment with interferon alpha-2b plus ribavirin in patients with chronic hepatitis C genotype 1b. Hepatol. Res. 33: 285291.
111. Negro, F. 2006. Mechanisms and significance of liver steatosis in hepatitis C virus infection. World J. Gastroenterol. 12: 67566765.
112. Neumann, U.,, G. Puhl,, M. Bahra,, T. Berg,, J. M. Langrehr,, R. Neuhaus, and, P. Neuhaus. 2006. Treatment of patients with recurrent hepatitis C after liver transplantation with peginterferon alfa-2B plus ribavirin. Transplantation 82: 4347.
113. Okamoto, T.,, Y. Nishimura,, T. Ichimura,, K. Suzuki,, T. Miyamura,, T. Suzuki,, K. Moriishi, and, Y. Matsuura. 2006. Hepatitis C virus RNA replication is regulated by FKBP8 and Hsp90. EMBO J. 25: 50155025.
114. Paradis, V.,, P. Mathurin,, M. Kollinger,, F. Imbert-Bismut,, F. Charlotte,, A. Piton,, P. Opolon,, A. Holstege,, T. Poynard, and, P. Bedossa. 1997. In situ detection of lipid peroxidation in chronic hepatitis C: correlation with pathological features. J. Clin. Pathol. 50: 401406.
115. Pavio, N.,, D. R. Taylor, and, M. M. Lai. 2002. Detection of a novel unglycosylated form of hepatitis C virus E2 envelope protein that is located in the cytosol and interacts with PKR. J. Virol. 76: 12651272.
116. Pavlovic, D.,, D. C. Neville,, O. Argaud,, B. Blumberg,, R. A. Dwek,, W. B. Fischer, and, N. Zitzmann. 2003. The hepatitis C virus p7 protein forms an ion channel that is inhibited by long-alkyl-chain iminosugar derivatives. Proc. Natl. Acad. Sci. USA 100: 61046108.
117. Pawlotsky, J. M. 2003. Diagnostic testing in hepatitis C virus infection: viral kinetics and genomics. Semin. Liver Dis. 23(Suppl.1): 311.
118. Pawlotsky, J. M. 2006. Hepatitis C virus population dynamics during infection. Curr. Top. Microbiol. Immunol. 299: 261284.
119. Pawlotsky, J. M. 2006. Therapy of hepatitis C: from empiricism to eradication. Hepatology 43: S207S220.
120. Pawlotsky, J. M.,, S. Chevaliez, and, J. G. McHutchison. 2007. The hepatitis C virus life cycle as a target for new antiviral therapies. Gastroenterology 132: 19791998.
121. Polyak, S. J. 2006. Resistance of hepatitis C virus to the host antiviral response. Future Med. 1: 8998.
122. Polyak, S. J.,, K. S. Khabar,, D. M. Paschal,, H. J. Ezelle,, G. Duverlie,, G. N. Barber,, D. E. Levy,, N. Mukaida, and, D. R. Gretch. 2001. Hepatitis C virus nonstructural 5A protein induces inter-leukin-8, leading to partial inhibition of the interferon-induced antiviral response. J. Virol. 75: 60956106.
123. Polyak, S. J.,, D. M. Paschal,, S. McArdle,, M. J. Gale, Jr.,, D. Moradpour, and, D. R. Gretch. 1999. Characterization of the effects of hepatitis C virus nonstructural 5A protein expression in human cell lines and on interferon-sensitive virus replication. Hepatology 29: 12621271.
124. Poynard, T.,, P. Bedossa,, P. Opolon, et al. 1997. Natural history of liver fibrosis progression in patients with chronic hepatitis C. Lancet 349: 825832.
125. Poynard, T.,, J. McHutchison,, Z. Goodman,, M. H. Ling,, J. Albrecht, et al. 2000. Is an “a la carte” combination interferon alfa-2b plus ribavirin regimen possible for the first line treatment in patients with chronic hepatitis C? Hepatology 31: 211218.
126. Poynard, T.,, V. Ratziu,, Y. Benhamou,, P. Opolon,, P. Cacoub, and, P. Bedossa. 2000. Natural history of HCV infection. Baillieres Best Pract. Res. Clin. Gastroenterol. 14: 211228.
127. Ramos, B.,, M. Nunez,, A. Rendon,, M. A. Berdun,, E. Losada,, I. Santos,, S. Echevarria,, A. Ocampo,, C. Miralles,, P. Arazo,, P. Barreiro,, M. Romero,, P. Labarga,, J. M. Guardiola,, J. Garcia-Samaniego, and, V. Soriano. 2007. Critical role of ribavirin for the achievement of early virological response to HCV therapy in HCV/HIV-coinfected patients. J. Viral Hepat. 14: 387391.
128. Reesink, H. W.,, S. Zeuzem,, C. J. Weegink,, N. Forestier,, A. van Vliet,, J. van de Wetering de Rooij,, L. McNair,, S. Purdy,, R. Kauffman,, J. Alam, and, P. L. Jansen. 2006. Rapid decline of viral RNA in hepatitis C patients treated with VX-950: a phase Ib, placebo-controlled, randomized study. Gastroenterology 131: 9971002.
129. Rehermann, B. 2007. Chronic infections with hepatotropic viruses: mechanisms of impairment of cellular immune responses. Semin. Liver Dis. 27: 152160.
130. Rehermann, B., and, M. Nascimbeni. 2005. Immunology of hepatitis B virus and hepatitis C virus infection. Nat. Rev. Immunol. 5: 215229.
131. Roberts, S.,, G. Cooksley,, R. Robson,, D. Shaw,, H. Berns,, M. Brandl,, S. Fettner,, G. Hill,, D. Ipe,, K. Klumpp,, M. Mannino,, E. O’Mara,, Y. Tu, and, C. Washington. 2006. Results of a phase 1b, multiple dose study of R1626, a novel nucleoside analogue targeting HCV polymerase in chronic HCV genotype-1 patients. Hepatology 44:S692A–S700A.
132. Rocca, P.,, F. Bailly,, M. Chevallier,, P. Chevallier,, F. Zoulim, and, C. Trepo. 2003. Early treatment of acute hepatitis C with inter-feron alpha-2b or interferon alpha-2b plus ribavirin: study of sixteen patients. Gastroenterol. Clin. Biol. 27: 294299. (In French.)
133. Ross, R. S.,, S. Viazov,, S. S. Kpakiwa, and, M. Roggendorf. 2007. Transcription-mediated amplification linked to line probe assay as a routine tool for HCV typing in clinical laboratories. J. Clin. Lab. Anal. 21: 340347.
134. Saadoun, D.,, F. Suarez,, F. Lefrere,, F. Valensi,, X. Mariette,, A. Aouba,, C. Besson,, B. Varet,, X. Troussard,, P. Cacoub, and, O. Hermine. 2005. Splenic lymphoma with villous lymphocytes, associated with type II cryoglobulinemia and HCV infection: a new entity? Blood 105: 7476.
135. Saito, T., and, M. Gale, Jr. 2008. Regulation of innate immunity against hepatitis C virus infection. Hepatol. Res. 38: 115122.
136. Saito, Y.,, V. Escuret,, D. Durantel,, F. Zoulim,, R. F. Schinazi, and, L. A. Agrofoglio. 2003. Synthesis of 1,2,3-triazolo-carbanucleo-side analogues of ribavirin targeting an HCV in replicon. Bioorg. Med. Chem. 11: 36333639.
137. Samuel, C. E. 2001. Antiviral actions of interferons. Clin. Micro-biol. Rev. 14: 778809.
138. Samuel, D.,, T. Bizollon,, C. Feray,, B. Roche,, S. N. Ahmed,, C. Lemonnier,, M. Cohard,, M. Reynes,, M. Chevallier,, C. Ducerf,, J. Baulieux,, M. Geffner,, J. K. Albrecht,, H. Bismuth, and, C. Trepo. 2003. Interferon-alpha 2b plus ribavirin in patients with chronic hepatitis C after liver transplantation: a randomized study. Gastroenterology 124: 642650.
139. Sanchez-Tapias, J. M.,, M. Diago,, P. Escartin,, J. Enriquez,, M. Romero-Gomez,, R. Barcena,, J. Crespo,, R. Andrade,, E. Martinez-Bauer,, R. Perez,, M. Testillano,, R. Planas,, R. Sola,, M. Garcia-Bengoechea,, J. Garcia-Samaniego,, M. Munoz-Sanchez, and, R. Moreno-Otero. 2006. Peginterferon-alfa2a plus ribavirin for 48 versus 72 weeks in patients with detectable hepatitis C virus RNA at week 4 of treatment. Gastroenterology 131: 451460.
140. Santantonio, T.,, M. Fasano,, E. Sinisi,, A. Guastadisegni,, C. Casalino,, M. Mazzola,, R. Francavilla, and, G. Pastore. 2005. Efficacy of a 24-week course of PEG-interferon alpha-2b monotherapy in patients with acute hepatitis C after failure of spontaneous clearance. J. Hepatol. 42: 329333.
141. Sarrazin, C.,, T. L. Kieffer,, D. Bartels,, B. Hanzelka,, U. Muh,, M. Welker,, D. Wincheringer,, Y. Zhou,, H. M. Chu,, C. Lin,, C. Weegink,, H. Reesink,, S. Zeuzem, and, A. D. Kwong. 2007. Dynamic hepatitis C virus genotypic and phenotypic changes in patients treated with the protease inhibitor telaprevir. Gastroenterology 132: 17671777.
142. Sarrazin, C.,, R. Rouzier,, F. Wagner,, N. Forestier,, D. Larrey,, S. K. Gupta,, M. Hussain,, A. Shah,, D. Cutler,, J. Zhang, and, S. Zeuzem. 2007. SCH 503034, a novel hepatitis C virus protease inhibitor, plus pegylated interferon alpha-2b for genotype 1 nonresponders. Gastroenterology 132: 12701278.
143. Schirren, C. A.,, R. Zachoval,, J. T. Gerlach,, A. Ulsenheimer,, N. H. Gruener,, H. M. Diepolder,, G. Baretton,, W. Schraut,, H. G. Rau,, H. Nitschko,, G. R. Pape, and, M. C. Jung. 2003. Antiviral treatment of recurrent hepatitis C virus (HCV) infection after liver transplantation: association of a strong, multispecific, and long-lasting CD4+ T cell response with HCV-elimination. J. Hepatol. 39: 397404.
144. Scott, J. D., and, D. R. Gretch. 2007. Molecular diagnostics of hepatitis C virus infection: a systematic review. JAMA 297: 724732.
145. Seeff, L. B. 2002. Natural history of chronic hepatitis C. Hepatology 36: S35S46.
146. Sen, G. C. 2001. Viruses and interferons. Annu. Rev. Microbiol. 55: 255281.
147. Sherman, M.,, L. Cohen,, M. A. Cooper,, M. Elkashab,, V. Feinman,, D. Fletcher,, N. Girgrah,, J. Heathcote,, M. Levstik,, W. B. McNaull,, D. Wong,, F. Wong, and, C. Yim. 2006. Clinical recommendations for the use of recombinant human erythropoietin in patients with hepatitis C virus being treated with ribavirin. Can. J. Gastroenterol. 20: 479485.
148. Shiffman, M. L.,, M. Diago,, A. Tran,, P. Pockros,, R. Reindollar,, D. Prati,, M. Rodriguez-Torres,, P. Lardelli,, S. Blotner, and, S. Zeuzem. 2006. Chronic hepatitis C in patients with persistently normal alanine transaminase levels. Clin. Gastroenterol. Hepatol. 4: 645652.
149. Shiffman, M. L.,, J. Salvatore,, S. Hubbard,, A. Price,, R. K. Sterling,, R. T. Stravitz,, V. A. Luketic, and, A. J. Sanyal. 2007. Treatment of chronic hepatitis C virus genotype 1 with peginterferon, ribavirin, and epoetin alpha. Hepatology 46: 371379.
150. Shiffman, M. L.,, F. Suter,, B. R. Bacon,, D. Nelson,, H. Harley,, R. Sola,, S. D. Shafran,, K. Barange,, A. Lin,, A. Soman, and, S. Zeuzem. 2007. Peginterferon alfa-2a and ribavirin for 16 or 24 weeks in HCV genotype 2 or 3. N. Engl. J. Med. 357: 124134.
151. Shiina, M., and, B. Rehermann. 2007. Cell culture-produced hepatitis C virus impairs plasmacytoid dendritic cell function. Hepatology 47: 385395.
152. Simmonds, P. 1997. Clinical relevance of hepatitis C virus genotypes. Gut 40: 291293.
153. Simmonds, P. 2004. Genetic diversity and evolution of hepatitis C virus—15 years on. J. Gen. Virol. 85: 31733188.
154. Simmonds, P.,, J. Bukh,, C. Combet,, G. Deleage,, N. Enomoto,, S. Feinstone,, P. Halfon,, G. Inchauspe,, C. Kuiken,, G. Maertens,, M. Mizokami,, D. G. Murphy,, H. Okamoto,, J. M. Pawlotsky,, F. Penin,, E. Sablon,, I. T. Shin,, L. J. Stuyver,, H. J. Thiel,, S. Viazov,, A. J. Weiner, and, A. Widell. 2005. Consensus proposals for a unified system of nomenclature of hepatitis C virus genotypes. Hepatology 42: 962973.
155. Spengler, U., and, J. Nattermann. 2007. Immunopathogenesis in hepatitis C virus cirrhosis. Clin. Sci. (London) 112: 141155.
156. Steinmann, E.,, F. Penin,, S. Kallis,, A. H. Patel,, R. Bartenschlager, and, T. Pietschmann. 2007. Hepatitis C virus p7 protein is crucial for assembly and release of infectious virions. PLoS Pathog. 3:e103.
157. Stelzl, E.,, C. van der Meer,, R. Gouw,, M. Beld,, M. Grahovac,, E. Marth, and, H. H. Kessler. 2007. Determination of the hepatitis C virus subtype: comparison of sequencing and reverse hybridization assays. Clin. Chem. Lab. Med. 45: 167170.
158. Sulkowski, M. S., and, Y. Benhamou. 2007. Therapeutic issues in HIV/HCV-coinfected patients. J. Viral Hepat. 14: 371386.
159. Sulkowski, M. S.,, S. H. Mehta,, M. S. Torbenson,, Y. Higgins,, S. C. Brinkley,, R. M. de Oca,, R. D. Moore,, N. H. Afdhal, and, D. L. Thomas. 2007. Rapid fibrosis progression among HIV/hepatitis C virus-co-infected adults. AIDS 21: 22092216.
160. Summers, J., and, S. Litwin. 2006. Examining the theory of error catastrophe. J. Virol. 80: 2026.
161. Szabo, G., and, A. Dolganiuc. 2006. HCV immunopathogenesis: virus-induced strategies against host immunity. Clin. Liver Dis. 10: 753771.
162. Tam, R. C.,, J. Y. Lau, and, Z. Hong. 2001. Mechanisms of action of ribavirin in antiviral therapies. Antivir. Chem. Chemother. 12: 261272.
163. Tam, R. C.,, B. Pai,, J. Bard,, C. Lim,, D. R. Averett,, U. T. Phan, and, T. Milovanovic. 1999. Ribavirin polarizes human T cell responses towards a Type 1 cytokine profile. J. Hepatol. 30: 376382.
164. Tardif, K. D.,, K. Mori, and, A. Siddiqui. 2002. Hepatitis C virus subgenomic replicons induce endoplasmic reticulum stress activating an intracellular signaling pathway. J. Virol. 76: 74537459.
165. Tardif, K. D.,, G. Waris, and, A. Siddiqui. 2005. Hepatitis C virus, ER stress, and oxidative stress. Trends Microbiol. 13: 159163.
166. Taylor, D. R.,, S. T. Shi,, P. R. Romano,, G. N. Barber, and, M. M. Lai. 1999. Inhibition of the interferon-inducible protein kinase PKR by HCV E2 protein. Science 285: 107110.
167. Thomas, D. L.,, J. Astemborski,, R. M. Rai,, F. A. Anania,, M. Schaeffer,, N. Galai,, K. Nolt,, K. E. Nelson,, S. A. Strathdee,, L. Johnson,, O. Laeyendecker,, J. Boitnott,, L. E. Wilson, and, D. Vlahov. 2000. The natural history of hepatitis C virus infection: host, viral, and environmental factors. JAMA 284: 450456.
168. Tong, X.,, R. Chase,, A. Skelton,, T. Chen,, J. Wright-Minogue, and, B. A. Malcolm. 2006. Identification and analysis of fitness of resistance mutations against the HCV protease inhibitor SCH 503034. Antivir. Res. 70: 2838.
169. Torriani, F. J.,, M. Rodriguez-Torres,, J. K. Rockstroh,, E. Lissen,, J. Gonzalez-Garcia,, A. Lazzarin,, G. Carosi,, J. Sasadeusz,, C. Katlama,, J. Montaner,, H. Sette, Jr.,, S. Passe,, J. De Pamphilis,, F. Duff,, U. M. Schrenk, and, D. T. Dieterich. 2004. Peginterferon Alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients. N. Engl. J. Med. 351: 438450.
170. Wang, C.,, M. Gale, Jr.,, B. C. Keller,, H. Huang,, M. S. Brown,, J. L. Goldstein, and, J. Ye. 2005. Identification of FBL2 as a geranylgeranylated cellular protein required for hepatitis C virus RNA replication. Mol. Cell 18: 425434.
171. Wang, X. H.,, D. M. Netski,, J. Astemborski,, S. H. Mehta,, M. S. Torbenson,, D. L. Thomas, and, S. C. Ray. 2007. Progression of fibrosis during chronic hepatitis C is associated with rapid virus evolution. J. Virol. 81: 65136522.
172. Washenberger, C. L.,, J. Q. Han,, K. J. Kechris,, B. K. Jha,, R. H. Silverman, and, D. J. Barton. 2007. Hepatitis C virus RNA: di-nucleotide frequencies and cleavage by RNase L. Virus Res. 130: 8595.
173. Watashi, K.,, N. Ishii,, M. Hijikata,, D. Inoue,, T. Murata,, Y. Miyanari, and, K. Shimotohno. 2005. Cyclophilin B is a functional regulator of hepatitis C virus RNA polymerase. Mol. Cell 19: 111122.
174. Watashi, K., and, K. Shimotohno. 2007. Chemical genetics approach to hepatitis C virus replication: cyclophilin as a target for anti-hepatitis C virus strategy. Rev. Med. Virol. 17: 245252.
175. Wiegand, J.,, P. Buggisch,, W. Boecher,, S. Zeuzem,, C. M. Gelb-mann,, T. Berg,, W. Kauffmann,, B. Kallinowski,, M. Cornberg,, E. Jaeckel,, H. Wedemeyer, and, M. P. Manns. 2006. Early mono-therapy with pegylated interferon alpha-2b for acute hepatitis C infection: the HEP-NET Acute-HCV-II study. Hepatology 43: 250256.
176. Wong, T., and, S. S. Lee. 2006. Hepatitis C: a review for primary care physicians. CMAJ 174: 649659.
177. Ye, J. 2007. Reliance of host cholesterol metabolic pathways for the life cycle of hepatitis C virus. PLoS Pathog. 3:e108.
178. Ye, J.,, C. Wang,, R. Sumpter, Jr.,, M. S. Brown,, J. L. Goldstein, and, M. Gale, Jr. 2003. Disruption of hepatitis C virus RNA replication through inhibition of host protein geranylgeranylation. Proc. Natl. Acad. Sci. USA 100: 1586515870.
179. Yu, J. W.,, G. Q. Wang,, L. J. Sun,, X. G. Li, and, S. C. Li. 2007. Predictive value of rapid virological response and early virological response on sustained virological response in HCV patients treated with pegylated interferon alpha-2a and ribavirin. J. Gastroenterol. Hepatol. 22: 832836.
180. Zeuzem, S.,, M. Buti,, P. Ferenci,, J. Sperl,, Y. Horsmans,, J. Cianciara,, E. Ibranyi,, O. Weiland,, S. Noviello,, C. Brass, and, J. Albrecht. 2006. Efficacy of 24 weeks treatment with peginterferon alfa-2b plus ribavirin in patients with chronic hepatitis C infected with genotype 1 and low pretreatment viremia. J. Hepatol. 44: 97103.
181. Zeuzem, S.,, G. Teuber,, U. Naumann,, T. Berg,, J. Raedle,, S. Hart-mann, and, U. Hopf. 2000. Randomized, double-blind, placebo-controlled trial of interferon alfa2a with and without amanta-dine as initial treatment for chronic hepatitis C. Hepatology 32: 835841.
182. Zhou, S.,, R. Liu,, B. M. Baroudy,, B. A. Malcolm, and, G. R. Reyes. 2003. The effect of ribavirin and IMPDH inhibitors on hepatitis C virus subgenomic replicon RNA. Virology 310: 333342.
183. Zhu, H.,, H. Dong,, E. Eksioglu,, A. Hemming,, M. Cao,, J. M. Crawford,, D. R. Nelson, and, C. Liu. 2007. Hepatitis C virus triggers apoptosis of a newly developed hepatoma cell line through antiviral defense system. Gastroenterology 133: 16491659.
184. Zoulim, F.,, M. Chevallier,, M. Maynard, and, C. Trepo. 2003. Clinical consequences of hepatitis C virus infection. Rev. Med. Virol. 13: 5768.


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Table 1.

Host and viral factors associated with SVR

Citation: Durantel D, Zoulim F. 2009. Clinical Aspects of Hepatitis C Virus Infection, p 241-264. In LaFemina, Ph. D. R (ed), Antiviral Research. ASM Press, Washington, DC. doi: 10.1128/9781555815493.ch14
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Table 2.

Main side effects of pegIFN and ribavirin

Citation: Durantel D, Zoulim F. 2009. Clinical Aspects of Hepatitis C Virus Infection, p 241-264. In LaFemina, Ph. D. R (ed), Antiviral Research. ASM Press, Washington, DC. doi: 10.1128/9781555815493.ch14
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Table 3.

Protease and polymerase inhibitors still in clinical trials or cancelled

Citation: Durantel D, Zoulim F. 2009. Clinical Aspects of Hepatitis C Virus Infection, p 241-264. In LaFemina, Ph. D. R (ed), Antiviral Research. ASM Press, Washington, DC. doi: 10.1128/9781555815493.ch14

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