Current and Future Hepatitis C Therapies

Archives of Medical Research

Volumn 38, Issue 6, 2007, Pages 678-690

  Firpi, Roberto J ^a   Nelson, David R ^a  

^a UNIVERSITY OF FLORIDA   (United States)

Author keywords

Hepatitis C inhibitors; Hepatitis C therapies; Immunomodulation; Interferon therapy; Polymerase inhibitors; Protease inhibitors

Indexed keywords

ALBUMIN ALPHA INTERFERON; ANTIRETROVIRUS AGENT; ANTIVIRUS AGENT; BETA INTERFERON; CILUPREVIR; CIVACIR; CONSENSUS INTERFERON; CPG 10101; GAMMA INTERFERON; GLYCOPROTEIN E1; GLYCOPROTEIN E2; GROWTH FACTOR; HCV 796; HEPATITIS C ANTIBODY; HEPATITIS C VACCINE; INTERFERON; IRON; ISIS 14803; MX 3256; NIM 811; OMEGA INTERFERON; PEGINTERFERON; PEGINTERFERON ALPHA2A; PEGINTERFERON ALPHA2B; R 1479; R 1626; RECOMBINANT ERYTHROPOIETIN; RIBAMIDINE; RIBAVIRIN; SCH 503034; UNCLASSIFIED DRUG; UNINDEXED DRUG; VALOPICITABINE; VX 950;

ANEMIA; ANTIBIOTIC RESISTANCE; ANTIVIRAL ACTIVITY; ANTIVIRAL THERAPY; CLEARANCE; CLINICAL TRIAL; COMBINATION CHEMOTHERAPY; CYTOPENIA; DRUG DOSE INCREASE; DRUG DOSE REDUCTION; DRUG HALF LIFE; DRUG INDICATION; DRUG MEGADOSE; DRUG TARGETING; DRUG TOLERABILITY; DRUG WITHDRAWAL; ERADICATION THERAPY; GASTROINTESTINAL SYMPTOM; GENOTYPE; HEMODIALYSIS; HEMODIALYSIS PATIENT; HEPATITIS C; HEPATITIS C VIRUS; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNOMODULATION; INTERNAL RIBOSOME ENTRY SITE; KIDNEY FAILURE; KINETICS; LIVER CELL; LIVER CIRRHOSIS; LIVER DISEASE; LIVER FIBROSIS; LOW DRUG DOSE; MONOTHERAPY; NONHUMAN; PATIENT COMPLIANCE; QUALITY OF LIFE; RACE DIFFERENCE; REVIEW; SUPERINFECTION; TREATMENT DURATION; TREATMENT RESPONSE; UNSPECIFIED SIDE EFFECT; VACCINATION; VIREMIA; VIRUS CELL INTERACTION; VIRUS INHIBITION; VIRUS LOAD; VIRUS REPLICATION;

ANTIVIRAL AGENTS; HEPACIVIRUS; HEPATITIS C, CHRONIC; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; IMMUNIZATION, PASSIVE; IMMUNOLOGIC FACTORS; INTERFERONS; NUCLEIC ACID SYNTHESIS INHIBITORS;

EID: 34347268432     PISSN: 01884409     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.arcmed.2006.09.002     Document Type: Review

References (120)

1. Rakela J., and Vargas H.E. Hepatitis C: magnitude of the problem. Liver Transpl 8 Suppl 1 (2002) S3-S6
2. Sangiovanni A., Prati G.M., Fasani P., Ronchi G., Romeo R., Manini M., et al. The natural history of compensated cirrhosis due to hepatitis C virus: A 17-year cohort study of 214 patients. Hepatology 43 (2006) 1303-1310
3. Davis G.L. Impact of HCV infection: projections into the next century. Hepatology 28 (1998) 390A
4. Choo Q.L., Kuo G., Weiner A.J., Overby L.R., Bradley D.W., and Houghton M. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science 244 (1989) 359-362
5. Hoofnagle J.H., Mullen K.D., Jones D.B., Rustgi V., Di Bisceglie A., Peters M., et al. Treatment of chronic non-A, non-B hepatitis with recombinant human alpha interferon. A preliminary report. N Engl J Med 315 (1986) 1575-1578
6. Fried M.W., Shiffman M.L., Reddy K.R., Smith C., Marinos G., Goncales Jr. F.L., et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 347 (2002) 975-982
7. Heathcote E.J., Shiffman M.L., Cooksley W.G., Dusheiko G.M., Lee S.S., Balart L., et al. Peginterferon alfa-2a in patients with chronic hepatitis C and cirrhosis. N Engl J Med 343 (2000) 1673-1680
8. Lindsay K.L., Trepo C., Heintges T., Shiffman M.L., Gordon S.C., Hoefs J.C., et al. A randomized, double-blind trial comparing pegylated interferon alfa-2b to interferon alfa-2b as initial treatment for chronic hepatitis C. Hepatology 34 (2001) 395-403
9. Recommendations from the National Institutes of Health consensus development conference statement: management of hepatitis C: 2002. Hepatology 36 (2002) 1039
10. National Institutes of Health Consensus Development Conference Statement: Management of hepatitis C: 2002-June 10-12, 2002. Hepatology 36 Suppl 1 (2002) S3-S20
11. Conjeevaram H.S., Fried M.W., Jeffers L.J., Terrault N.A., Wiley-Lucas T.E., Afdhal N., et al. Peginterferon and ribavirin treatment in african american and caucasian american patients with hepatitis C genotype 1. Gastroenterology 131 (2006) 470-477
12. Jeffers L.J., Cassidy W., Howell C.D., Hu S., and Reddy K.R. Peginterferon alfa-2a (40 kd) and ribavirin for black American patients with chronic HCV genotype 1. J Hepatol 39 (2004) 1702-1708
13. Muir A.J., Bornstein J.D., and Killenberg P.G. Peginterferon alfa-2b and ribavirin for the treatment of chronic hepatitis C in blacks and non-Hispanic whites. N Engl J Med 350 (2004) 2265-2271
14. Srivastava S., Bertagnolli M., and Lewis J.H. Sustained virological response rate to pegylated interferon plus ribavirin for chronic hepatitis C in African Americans: results in treatment-naive patients in a university liver clinic. J Natl Med Assoc 97 (2005) 1703-1707
15. Layden-Almer J.E., Cotler S.J., and Layden T.J. Viral kinetics in the treatment of chronic hepatitis C. J Viral Hepat 13 (2006) 499-504
16. Layden-Almer J.E., and Layden T.J. Viral kinetics in hepatitis C virus: special patient populations. Semin Liver Dis 23 Suppl 1 (2003) 29-33
17. Lam N.P., Neumann A.U., Gretch D.R., Wiley T.E., Perelson A.S., and Layden T.J. Dose-dependent acute clearance of hepatitis C genotype 1 virus with interferon alfa. Hepatology 26 (1997) 226-231
18. Neumann A.U., Lam N.P., Dahari H., Gretch D.R., Wiley T.E., Layden T.J., et al. Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-alpha therapy. Science 282 (1998) 103-107
19. Zeuzem S., Herrmann E., Lee J.H., Fricke J., Neumann A.U., Modi M., et al. Viral kinetics in patients with chronic hepatitis C treated with standard or peginterferon alpha2a. Gastroenterology 120 (2001) 1438-1447
20. Herrmann E., Lee J.H., Marinos G., Modi M., and Zeuzem S. Effect of ribavirin on hepatitis C viral kinetics in patients treated with pegylated interferon. Hepatology 37 (2003) 1351-1358
21. Davis G.L., Wong J.B., McHutchison J.G., Manns M.P., Harvey J., and Albrecht J. Early virologic response to treatment with peginterferon alfa-2b plus ribavirin in patients with chronic hepatitis C. Hepatology 38 (2003) 645-652
22. McHutchison J.G., Shad J.A., Gordon S.C., Morgan T.R., Ling M.H., Garaud J.J., et al. Predicting response to initial therapy with interferon plus ribavirin in chronic hepatitis C using serum HCV RNA results during therapy. J Viral Hepat 8 (2001) 414-420
23. Shiffman M.L., Diago M., Tran A., Pockros P., Reindollar R., Prati D., et al. Chronic hepatitis C in patients with persistently normal alanine transaminase levels. Clin Gastroenterol Hepatol 4 (2006) 645-652
24. Persico M., Perrotta S., Persico E., Terracciano L., Folgori A., Ruggeri L., et al. Hepatitis C virus carriers with persistently normal ALT levels: biological peculiarities and update of the natural history of liver disease at 10 years. J Viral Hepat 13 (2006) 290-296
25. Jacobson I.M., Ahmed F., Russo M.W., Lebovics E., Dieterich D.T., Esposito S.P., et al. Interferon alfa-2b [correction of alpha-2b] and ribavirin for patients with chronic hepatitis C and normal ALT. Am J Gastroenterol 99 (2004) 1700-1705
26. Strader D.B., Wright T., Thomas D.L., and Seeff L.B. Diagnosis, management, and treatment of hepatitis C. Hepatology 39 (2004) 1147-1171
27. Berg T., von Wagner M., Nasser S., Sarrazin C., Heintges T., Gerlach T., et al. Extended treatment duration for hepatitis C virus type 1: comparing 48 versus 72 weeks of peginterferon-alfa-2a plus ribavirin. Gastroenterology 130 (2006) 1086-1097
28. Sanchez-Tapias J.M., Diago M., Escartin P., Enriquez J., Romero-Gomez M., Barcena R., et al. Peginterferon-alfa2a plus ribavirin for 48 versus 72 weeks in patients with detectable hepatitis C virus RNA at week 4 of treatment. Gastroenterology 131 (2006) 451-460
29. Jensen D.M., Morgan T.R., Marcellin P., Pockros P.J., Reddy K.R., Hadziyannis S.J., et al. Early identification of HCV genotype 1 patients responding to 24 weeks peginterferon alpha-2a (40 kd)/ribavirin therapy. Hepatology 43 (2006) 954-960
30. Ferenci P., Berholz U., Laferl H., Scherzer T.M., Maieron A., Gschwantler M., et al. 24 Week treatment regimen with peginterferon alpha-2a (40-KD) (Pegasys) plus ribavirin (Copegus) in HCV genotype 1 or 4 'super-responders'. J Hepatol 44 Suppl 2 (2006) S6
31. Hadziyannis S.J., Sette Jr. H., Morgan T.R., Balan V., Diago M., Marcellin P., et al. Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med 140 (2004) 346-355
32. Dalgard O., Bjoro K., Hellum K.B., Myrvang B., Ritland S., Skaug K., et al. Treatment with pegylated interferon and ribavarin in HCV infection with genotype 2 or 3 for 14 weeks: a pilot study. Hepatology 40 (2004) 1260-1265
33. Mangia A., Santoro R., Minerva N., Ricci G.L., Carretta V., Persico M., et al. Peginterferon alfa-2b and ribavirin for 12 vs. 24 weeks in HCV genotype 2 or 3. N Engl J Med 352 (2005) 2609-2617
34. von Wagner M., Huber M., Berg T., Hinrichsen H., Rasenack J., Heintges T., et al. Peginterferon-alpha-2a (40KD) and ribavirin for 16 or 24 weeks in patients with genotype 2 or 3 chronic hepatitis C. Gastroenterology 129 (2005) 522-527
35. Shiffman M.L., Pappas S., Nyberg L., Greenbloom S., Gibas A., Bacon B., et al. Peginterferon alpha-2a (Pegasys) plus ribavirin (Copegus) for 16 or 24 weeks in patients with HCV genotype 2 or 3. Final results of the ACCELERATE Trial. J Hepatol 44 (2006) S271
36. Ferenci P., Fried M.W., Shiffman M.L., Smith C.I., Marinos G., Goncales Jr. F.L., et al. Predicting sustained virological responses in chronic hepatitis C patients treated with peginterferon alfa-2a (40 KD)/ribavirin. J Hepatol 43 (2005) 425-433
37. McHutchison J.G., Manns M., Patel K., Poynard T., Lindsay K.L., Trepo C., et al. Adherence to combination therapy enhances sustained response in genotype-1-infected patients with chronic hepatitis C. Gastroenterology 123 (2002) 1061-1069
38. Afdhal N.H., Dieterich D.T., Pockros P.J., Schiff E.R., Shiffman M.L., Sulkowski M.S., et al. Epoetin alfa maintains ribavirin dose in HCV-infected patients: a prospective, double-blind, randomized controlled study. Gastroenterology 126 (2004) 1302-1311
39. Pockros P.J., Shiffman M.L., Schiff E.R., Sulkowski M.S., Younossi Z., Dieterich D.T., et al. Epoetin alfa improves quality of life in anemic HCV-infected patients receiving combination therapy. Hepatology 40 (2004) 1450-1458
40. Shiffman M.L., Di Bisceglie A.M., Lindsay K.L., Morishima C., Wright E.C., Everson G.T., et al. Peginterferon alfa-2a and ribavirin in patients with chronic hepatitis C who have failed prior treatment. Gastroenterology 126 (2004) 1015-1023
41. Jacobson I.M., Gonzalez S.A., Ahmed F., Lebovics E., Min A.D., Bodenheimer Jr. H.C., et al. A randomized trial of pegylated interferon alpha-2b plus ribavirin in the retreatment of chronic hepatitis C. Am J Gastroenterol 100 (2005) 2453-2462
42. Taliani G., Gemignani G., Ferrari C., Aceti A., Bartolozzi D., Blanc P.L., et al. Pegylated interferon alfa-2b plus ribavirin in the retreatment of interferon-ribavirin nonresponder patients. Gastroenterology 130 (2006) 1098-1106
43. Sherman M., Yoshida E.M., Deschenes M., Krajden M., Bain V., Peltekian K., et al. Peginterferon alfa-2a (40KD) plus ribavirin in chronic hepatitis C patients who failed previous interferon therapy. Gut 55 (2006) 1631-1638
44. Pockros P.J., Reindollar R., McHutchinson J., Reddy R., Wright T., Boyd D.G., et al. The safety and tolerability of daily infergen plus ribavirin in the treatment of naiive chronic hepatitis C patients. J Viral Hepat 10 (2003) 55-60
45. Cornberg M., Hadem J., Herrmann E., Schuppert F., Schmidt H.H., Reiser M., et al. Treatment with daily consensus interferon (CIFN) plus ribavirin in non-responder patients with chronic hepatitis C: a randomized open-label pilot study. J Hepatol 44 (2006) 291-301
46. Bocher W.O., Schuchmann M., Link R., Hillenbrand H., Rahman F., Sprinzl M., et al. Consensus interferon and ribavirin for patients with chronic hepatitis C and failure of previous interferon-alpha therapy. Liver Int 26 (2006) 319-325
47. Everson G.T., Trotter J., Forman L., Kugelmas M., Halprin A., Fey B., et al. Treatment of advanced hepatitis C with a low accelerating dosage regimen of antiviral therapy. Hepatology 42 (2005) 255-262
48. Fontana R.J., Everson G.T., Tuteja S., Vargas H.E., and Shiffman M.L. Controversies in the management of hepatitis C patients with advanced fibrosis and cirrhosis. Clin Gastroenterol Hepatol 2 (2004) 183-197
49. Arthur M.J. Reversibility of liver fibrosis and cirrhosis following treatment for hepatitis C. Gastroenterology 122 (2002) 1525-1528
50. Poynard T., McHutchison J., Manns M., Trepo C., Lindsay K., Goodman Z., et al. Impact of pegylated interferon alfa-2b and ribavirin on liver fibrosis in patients with chronic hepatitis C. Gastroenterology 122 (2002) 1303-1313
51. Everson G.T., Trouillot T., Trotter J., Skilbred J., Halprin A., McKinley C., et al. Treatment of decompensated cirrhotics with a slow-accelerating dose regimen of interferon-alfa-2b plus ribavirin: safety and efficacy. Hepatology 32 (2000) 308A
52. Crippin J.S., McCashland T., Terrault N., Sheiner P., and Charlton M.R. A pilot study of the tolerability and efficacy of antiviral therapy in hepatitis C virus-infected patients awaiting liver transplantation. Liver Transpl 8 (2002) 350-355
53. Martin P., and Fabrizi F. Treatment of chronic hepatitis C infection in patients with renal failure. Clin Gastroenterol Hepatol 3 Suppl 2 (2005) S113-S117
54. Fabrizi F., Poordad F.F., and Martin P. Hepatitis C infection and the patient with end-stage renal disease. Hepatology 36 (2002) 3-10
55. Rocha C.M., Perez R.M., Ferreira A.P., Carvalho-Filho R.J., Pace F.H., Silva I.S., et al. Efficacy and tolerance of interferon-alpha in the treatment of chronic hepatitis C in end-stage renal disease patients on hemodialysis. Liver Int 26 (2006) 305-310
56. Fabrizi F., Dulai G., Dixit V., Bunnapradist S., and Martin P. Meta-analysis: interferon for the treatment of chronic hepatitis C in dialysis patients. Aliment Pharmacol Ther 18 (2003) 1071-1081
57. Russo M.W., Goldsweig C.D., Jacobson I.M., and Brown Jr. R.S. Interferon monotherapy for dialysis patients with chronic hepatitis C: an analysis of the literature on efficacy and safety. Am J Gastroenterol 98 (2003) 1610-1615
58. Bruchfeld A., Stahle L., Andersson J., and Schvarcz R. Ribavirin treatment in dialysis patients with chronic hepatitis C virus infection-a pilot study. J Viral Hepat 8 (2001) 287-292
59. Sporea I., Popescu A., Sirli R., Golea O., Totolici C., Danila M., et al. Pegylated-interferon alpha 2a treatment for chronic hepatitis C in patients on chronic haemodialysis. World J Gastroenterol 12 (2006) 4191-4194
60. Kokoglu O.F., Ucmak H., Hosoglu S., Cetinkaya A., Kantarceken B., Buyukbese M.A., et al. Efficacy and tolerability of pegylated-interferon alpha-2a in hemodialysis patients with chronic hepatitis C. J Gastroenterol Hepatol 21 (2006) 575-580
61. Bruchfeld A., Lindahl K., Reichard O., Carlsson T., and Schvarcz R. Pegylated interferon and ribavirin treatment for hepatitis C in haemodialysis patients. J Viral Hepat 13 (2006) 316-321
62. Russo M.W., Ghalib R., Sigal S., and Joshi V. Randomized trial of pegylated interferon alpha-2b monotherapy in haemodialysis patients with chronic hepatitis C. Nephrol Dial Transplant 21 (2006) 437-443
63. Annicchiarico B.E., and Siciliano M. Pegylated interferon-alpha 2b monotherapy for haemodialysis patients with chronic hepatitis C. Aliment Pharmacol Ther 20 (2004) 123-124
64. Potthoff A., Wiegand J., Luth J.B., Wedemeyer H., Manns M.P., and Tillmann H.L. Superiority of standard interferon-alpha2b compared to pegylated interferon-alpha2b (12 kDa) in a hemodialysis patient with chronic hepatitis C?. Clin Nephrol 63 (2005) 232-235
65. Benhamou Y., Di Martino V., Bochet M., Colombet G., Thibault V., Liou A., et al. Factors affecting liver fibrosis in human immunodeficiency virus-and hepatitis C virus-coinfected patients: impact of protease inhibitor therapy. Hepatology 34 (2001) 283-287
66. Sherman K.E. Treatment of hepatitis C virus and human immunodeficiency virus co-infection. Clin Gastroenterol Hepatol 3 Suppl 2 (2005) S118-S121
67. Torriani F.J., Rodriguez-Torres M., Rockstroh J.K., Lissen E., Gonzalez-Garcia J., Lazzarin A., et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients. N Engl J Med 351 (2004) 438-450
68. Carrat F., Bani-Sadr F., Pol S., Rosenthal E., Lunel-Fabiani F., Benzekri A., et al. 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 (2004) 2839-2848
69. Chung R.T., Andersen J., Volberding P., Robbins G.K., Liu T., Sherman K.E., et al. Peginterferon alfa-2a plus ribavirin versus interferon alfa-2a plus ribavirin for chronic hepatitis C in HIV-coinfected persons. N Engl J Med 351 (2004) 451-459
70. Laguno M., Murillas J., Blanco J.L., Martinez E., Miquel R., Sanchez-Tapias J.M., et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for treatment of HIV/HCV co-infected patients. AIDS 18 (2004) F27-F36
71. Moreno L., Quereda C., Moreno A., Perez-Elias M.J., Antela A., Casado J.L., et al. Pegylated interferon alpha2b plus ribavirin for the treatment of chronic hepatitis C in HIV-infected patients. AIDS 18 (2004) 67-73
72. Perez-Olmeda M., Nunez M., Romero M., Gonzalez J., Castro A., Arribas J.R., et al. Pegylated IFN-alpha2b plus ribavirin as therapy for chronic hepatitis C in HIV-infected patients. AIDS 17 (2003) 1023-1028
73. Pawlotsky J.M. Therapy of hepatitis C: from empiricism to eradication. Hepatology 43 Suppl 1 (2006) S207-S220
74. Balan V., Nelson D.R., Sulkowski M.S., Everson G.T., Lambiase L.R., Wiesner R.H., et al. A phase I/II study evaluating escalating doses of recombinant human albumin-interferon-alpha fusion protein in chronic hepatitis C patients who have failed previous interferon-alpha-based therapy. Antivir Ther 11 (2006) 35-45
75. Moreno-Otero R., Trapero-Marugan M., Gomez-Dominguez E., Garcia-Buey L., and Moreno-Monteagudo J.A. Is interferon-beta an alternative treatment for chronic hepatitis C?. World J Gastroenterol 12 (2006) 2730-2736
76. Bain V.G., Kaita K.D., Yoshida E.M., Swain M.G., Heathcote E.J., Neumann A.U., et al. A phase 2 study to evaluate the antiviral activity, safety, and pharmacokinetics of recombinant human albumin-interferon alfa fusion protein in genotype 1 chronic hepatitis C patients. J Hepatol 44 (2006) 671-678
77. Gish R.G., Nelson D., Arora S., Fried M.W., Reddy K.R., Xu Y., et al. Virologic response and safety outcomes in therapy-naive patients treated for chronic hepatitis C with Viramidine in combination with pegylated interferon alfa-2a. Gastroenterology 128 (2005) 11
78. Benhamou Y., Pockros P., Rodriguez-Torres M., Gordon S.C., Shiffman M.L., Lurie Y., et al. The safety and efficacy of Viramidine plus pegylated interferon alpha-2B versus ribavirin plus pegylated interferon alpha-2B in therapy-naive patients infected with HCV: phase 3 results. J Hepatol 44 Suppl 2 (2006) S273
79. Bartosch B., and Cosset F.L. Cell entry of hepatitis C virus. Virology 348 (2006) 1-12
80. Heo T.H., Lee S.M., Bartosch B., Cosset F.L., and Kang C.Y. Hepatitis C virus E2 links soluble human CD81 and SR-B1 protein. Virus Res 121 (2006) 58-64
81. Davis G.L., Nelson D.R., Terrault N., Pruett T.L., Schiano T.D., Fletcher C.V., et al. A randomized, open-label study to evaluate the safety and pharmacokinetics of human hepatitis C immune globulin (Civacir) in liver transplant recipients. Liver Transpl 11 (2005) 941-949
82. Schiano T.D., Charlton M., Younossi Z., Galun E., Pruett T., Tur-Kaspa R., et al. Monoclonal antibody HCV-Ab(XTL)68 in patients undergoing liver transplantation for HCV: results of a phase 2 randomized study. Liver Transpl 12 (2006) 1381-1389
83. Leroux-Roels G., Depla E., Hulstaert F., Tobback L., Dincq S., Desmet J., et al. A candidate vaccine based on the hepatitis C E1 protein: tolerability and immunogenicity in healthy volunteers. Vaccine 22 (2004) 3080-3086
84. Nevens F., Roskams T., Van Vlierberghe H., Horsmans Y., Sprengers D., Elewaut A., et al. A pilot study of therapeutic vaccination with envelope protein E1 in 35 patients with chronic hepatitis C. Hepatology 38 (2003) 1289-1296
85. Fukushi S., Kurihara C., Ishiyama N., Hoshino F.B., Oya A., and Katayama K. The sequence element of the internal ribosome entry site and a 25-kilodalton cellular protein contribute to efficient internal initiation of translation of hepatitis C virus RNA. J Virol 71 (1997) 1662-1666
86. Tong M., Schiff E., Jensen D.M., Jacobson I., Everson G., and McHutchison J.G. Preliminary analysis of a phase II study of HEPTAZYME, a nuclease resistant ribozyme targeting HCV RNA. Hepatology 36 (2002) 788
87. McHutchison J.G., Patel K., Pockros P., Nyberg L., Pianko S., Yu R.Z., et al. A phase I trial of an antisense inhibitor of hepatitis C virus (ISIS 14803), administered to chronic hepatitis C patients. J Hepatol 44 (2006) 88-96
88. Hinrichsen H., Benhamou Y., Wedemeyer H., Reiser M., Sentjens R.E., Calleja J.L., et al. Short-term antiviral efficacy of BILN 2061, a hepatitis C virus serine protease inhibitor, in hepatitis C genotype 1 patients. Gastroenterology 127 (2004) 1347-1355
89. Lin K., Perni R.B., Kwong A.D., and Lin C. VX-950, a novel hepatitis C virus (HCV) NS3-4A protease inhibitor, exhibits potent antiviral activities in HCv replicon cells. Antimicrob Agents Chemother 50 (2006) 1813-1822
90. Malcolm B.A., Liu R., Lahser F., Agrawal S., Belanger B., Butkiewicz N., et al. SCH 503034, a mechanism-based inhibitor of hepatitis C virus NS3 protease, suppresses polyprotein maturation and enhances the antiviral activity of alpha interferon in replicon cells. Antimicrob Agents Chemother 50 (2006) 1013-1020
91. Perni R.B., Almquist S.J., Byrn R.A., Chandorkar G., Chaturvedi P.R., Courtney L.F., et al. Preclinical profile of VX-950, a potent, selective, and orally bioavailable inhibitor of hepatitis C virus NS3-4A serine protease. Antimicrob Agents Chemother 50 (2006) 899-909
92. Reesink H., Zeuzem S., Weegink C., Foresteir N., van Vliet A., and van de Wetering de Rooij J. Final results of a phase IB, multiple-dose study of VX-950, a hepatitis C virus protease inhibitor. Hepatology 42 Suppl 1 (2005) 234A-235A
93. Zeuzem S., Sarrazin C., Rouzier R., Tarral A., Brion N., and Foresteir N. Antiviral activity of SCH-503034, a HCV protease inhibitor administered as monotherapy in hepatitis C genotype 1 (HCV-1) patients refractory to pegylated interferon. Hepatology 42 Suppl 2 (2005) 233A-234A
94. Reesink H., Zeuzem S., van Vliet A., McNair L., Purdy S., Chu H.M., et al. Initial results of a phase 1B, multiple-dose study of VX-950, a hepatitis C virus protease inhibitor. Gastroenterology 128 Suppl 2 (2005) A-697
95. Reesink H., Zeuzem S., Weegink C., Foresteir N., van Vliet A., van de Wetering de Rooij J., et al. Final results of a phase 1B, multi-dose study of VX-950, a hepatitis C virus protease inhibitor. Hepatology 42 Suppl 1 (2005) 234A-235A
96. Reesink H., Foresteir N., Weegink C., Zeuzem S., McNair L., Purdy S., et al. Initial results of a 14-day study of the hepatitis C virus protease inhibitor VX-950, in combination with peginterferon-alpha-2a. J Hepatol 44 Suppl 2 (2006) S272
97. Zeuzem S., Sarrazin C., Wagner F., Rouzier R., Foresteir N., Gupta S., et al. The HCV NS3 protaese inhibitor SCH 503034 in combination with PEG-IFN alpha-2b in the treatment of HCV-1 PEG-IFN alpha-2b non-responders: antiviral activity and HCV variant analysis. J Hepatol 44 Suppl 2 (2006) S35
98. Bogen S.L., Arasappan A., Bennett F., Chen K., Jao E., Liu Y.T., et al. Discovery of SCH446211 (SCH6): a new ketoamide inhibitor of the HCV NS3 serine protease and HCV subgenomic RNA replication. J Med Chem 49 (2006) 2750-2757
99. Afdhal N., Godofsky E., Dienstag J., Rustgi V., Shick L., Duncan L., et al. Final phase I/II trial results for NM-283, a new antiviral for hepatitis C: antiviral efficacy and tolerance in patients with HCV-1 infection, including previous interferon failures. Hepatology 40 Suppl 1 (2004) 726A
100. O'Brien C., Godofsky E., Rodriguez-Torres M., Afdhal N., Pappas S., Pockros P., et al. Randomized trial of Valopicitabine (NM283), alone or with PEG-interferon, vs. retreatment with PEG-interferon plus ribavirin (PEGIFN/RBV) in hepatitis C patients with previous non-response to PEGIFN/RBV: first interim results. Hepatology 42 Suppl 1 (2005) 234A
101. Dieterich D.T., Lawitz E., Nguyen T., Younes Z., Santoro J., Gitlin N., et al. Early clearance of HCV RNA with Valopicitabine (NM283) plus PEG-interferon in treatment-naive patients with HCV-1 infection: first results from a phase IIb trial. J Hepatol 44 Suppl 2 (2006) S271-S272
102. Roberts S., Cooksley G., Shaw D., Berns H.K., Brandl M.T., Fettner S.H., et al. Interim results of a multiple ascending dose study of R1626, a novel nucleoside analog targeting HCV polymerase in chronic HCV patients. J Hepatol 44 Suppl 2 (2006) S269
103. Chandra P., Raible D., Harper D., Speth J., and Villano S. Antiviral activity of the non-nucleoside polymerase inhibitor, HCV-796, in patients with chronic hepatitis C virus: preliminary results from a randomized, double-blind, placebo-controlled, ascending multiple dose study. Gastroenterology 130 Suppl 2 (2006) A-748
104. ViroPharma Incorporated. ViroPharma Announces Positive Data from Phase 1b Combination Study of HCV-796 and Pegylated Interferon in Hepatitis C Patients (2006) 8-28
105. Firpi R.J., Zhu H., Morelli G., Abdelmalek M.F., Soldevila-Pico C., Machicao V.I., et al. Cyclosporine suppresses hepatitis C virus in vitro and increases the chance of a sustained virological response after liver transplantation. Liver Transpl 12 (2006) 51-57
106. Watashi K., Hijikata M., Hosaka M., Yamaji M., and Shimotohno K. Cyclosporin A suppresses replication of hepatitis C virus genome in cultured hepatocytes. Hepatology 38 (2003) 1282-1288
107. Inoue K., Sekiyama K., Yamada M., Watanabe T., Yasuda H., and Yoshiba M. Combined interferon alpha2b and cyclosporin A in the treatment of chronic hepatitis C: controlled trial. J Gastroenterol 38 (2003) 567-572
108. Cotler S.J., Morrissey M.J., Wiley T.E., Layden T.J., and Jensen D.M. A pilot study of the combination of cyclosporin A and interferon alfacon-1 for the treatment of hepatitis C in previous nonresponder patients. J Clin Gastroenterol 36 (2003) 352-355
109. Goto K., Watashi K., Murata T., Hishiki T., Hijikata M., and Shimotohno K. Evaluation of the anti-hepatitis C virus effects of cyclophilin inhibitors, cyclosporin A, and NIM811. Biochem Biophys Res Commun 343 (2006) 879-884
110. Whitby K., Taylor D., Patel D., Ahmed P., and Tyms A.S. Action of celgosivir (6 O-butanoyl castanospermine) against the pestivirus BVDV: implications for the treatment of hepatitis C. Antivir Chem Chemother 15 (2004) 141-151
111. Yoshida E.M., Kunimoto D., Lee S.S., Sherman M., Heathcote E.J., and Enns R. Results of a phase II dose ranging study of orally administered Celgosivir as monotherapy in chronic hepatitis C genotype-1 patients. Gastroenterology 130 Suppl 2 (2006) A-784
112. Nelson D.R., Marousis C.G., Ohno T., Davis G.L., and Lau J.Y. Intrahepatic hepatitis C virus-specific cytotoxic T lymphocyte activity and response to interferon alfa therapy in chronic hepatitis C. Hepatology 28 (1998) 225-230
113. Gale Jr. M., and Foy E.M. Evasion of intracellular host defence by hepatitis C virus. Nature 436 (2005) 939-945
114. Lee J., Wu C.C., Lee K.J., Chuang T.H., Katakura K., Liu Y.T., et al. Activation of anti-hepatitis C virus responses via Toll-like receptor 7. Proc Natl Acad Sci USA 103 (2006) 1828-1833
115. Horsmans Y., Berg T., Desager J.P., Mueller T., Schott E., Fletcher S.P., et al. Isatoribine, an agonist of TLR7, reduces plasma virus concentration in chronic hepatitis C infection. Hepatology 42 (2005) 724-731
116. McHutchinson J., Bacon B., Gordon S.C., Lawitz E., Shiffman M.L., Afdhal N.H., et al. Final results of a multi-center phase 1B, randomized, placebo-controlled, dose-escalation trial of CPG 10101 in patients with chronic hepatitis C virus. J Hepatol 44 Suppl 2 (2006) S49
117. McHutchinson J., Ghalib R., Lawitz E., Kwo P., Freilich B., Muir A.J., et al. Early viral response to CPG 10101, in combination with pegylated interferon and/or ribavirin, in chronic HCV genotype 1 infected patients with prior relapse. J Hepatol 44 Suppl 2 (2006) S269
118. Kapadia S.B., and Chisari F.V. Hepatitis C virus RNA replication is regulated by host geranylgeranylation and fatty acids. Proc Natl Acad Sci USA 102 (2005) 2561-2566
119. Ikeda M., Abe K., Yamada M., Dansako H., Naka K., and Kato N. Different anti-HCV profiles of statins and their potential for combination therapy with interferon. Hepatology 44 (2006) 117-125
120. Khorashadi S., Hasson N.K., and Cheung R.C. Incidence of statin hepatotoxicity in patients with hepatitis C. Clin Gastroenterol Hepatol 4 (2006) 902-907