Review article: Investigational agents for chronic hepatitis C

Alimentary Pharmacology and Therapeutics

Volumn 29, Issue 7, 2009, Pages 689-705

  Thompson, A J V ^a   McHutchison, J G ^a  

^a DUKE CLINICAL RESEARCH INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4' AZIDOCYTIDINE 2',3',5' TRIISOBUTYRATE; 5 CYCLOPROPYL 2 (4 FLUOROPHENYL) 6 [N (2 HYDROXYETHYL)METHANESULFONAMIDO] N METHYLBENZOFURAN 3 CARBOXAMIDE; ACH 806; ALBINTERFERON ALPHA2B; ANTIVIRUS AGENT; BAVITUXIMAB; BOCEPREVIR; CILUPREVIR; GS 9132; GS 9190; IMMUNOMODULATING AGENT; ISIS 14803; ITMN 191; MK 7009; NITAZOXANIDE; NONSTRUCTURAL PROTEIN 3; NONSTRUCTURAL PROTEIN 4A; PEGINTERFERON ALPHA; PEGINTERFERON ALPHA2B; PF 868554; PLACEBO; PROTEINASE INHIBITOR; R 7128; RIBAVIRIN; TARIBAVIRIN; TELAPREVIR; TMC 435350; UNCLASSIFIED DRUG; UNINDEXED DRUG; VALOPICITABINE; VCH 759; VX 500;

ANEMIA; ANTIVIRAL ACTIVITY; ARTICLE; BLOOD TOXICITY; CHILL; CLINICAL TRIAL; COUGHING; DIARRHEA; DOSE RESPONSE; DRUG DOSE COMPARISON; DRUG DOSE ESCALATION; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG HALF LIFE; DRUG INHIBITION; DRUG MEGADOSE; DRUG SAFETY; DRUG TARGETING; DRUG TOLERABILITY; DRUG WITHDRAWAL; DYSGEUSIA; DYSPNEA; FATIGUE; GASTROINTESTINAL SYMPTOM; GENOTYPE; HEADACHE; HEPATITIS C; HEPATITIS C VIRUS; HUMAN; LEUKOPENIA; LIVER TOXICITY; LOW DRUG DOSE; MEDLINE; MONOTHERAPY; MULTIPLE CYCLE TREATMENT; NAUSEA; NEPHROTOXICITY; NEUTROPENIA; POINT MUTATION; PRIORITY JOURNAL; PRURITUS; RASH; TREATMENT DURATION; TREATMENT RESPONSE; UNSPECIFIED SIDE EFFECT; VIRUS INHIBITION; VIRUS LOAD; VIRUS REPLICATION; VIRUS RESISTANCE; VOMITING;

ANTIVIRAL AGENTS; CLINICAL TRIALS AS TOPIC; DRUG DESIGN; DRUGS, INVESTIGATIONAL; HEPATITIS C, CHRONIC; HUMANS; VIRUS REPLICATION;

EID: 61849120770     PISSN: 02692813     EISSN: 13652036     Source Type: Journal    
DOI: 10.1111/j.1365-2036.2009.03927.x     Document Type: Article

References (96)

1. Sy T, Jamal MM. Epidemiology of hepatitis C virus (HCV) infection. Int J Med Sci 2006 3 : 41 6.
2. Pawlotsky JM, Chevaliez S, McHutchison JG. The hepatitis C virus life cycle as a target for new antiviral therapies. Gastroenterology 2007 132 : 1979 98.
3. Kim WR. The burden of hepatitis C in the United States. Hepatology 2002 36 (Suppl. 1 S30 4.
4. Davis GL. Chronic hepatitis C and liver transplantation. Rev Gastroenterol Disord 2004 4 : 7 17.
5. Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 2001 358 : 958 65.
6. Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002 347 : 975 82.
7. Alter MJ, Kruszon-Moran D, Nainan OV, et al. The prevalence of hepatitis C virus infection in the United States, 1988 through 1994. N Engl J Med 1999 341 : 556 62.
8. Strader DB, Wright T, Thomas DL, Seeff LB. Diagnosis, management, and treatment of hepatitis C. Hepatology 2004 39 : 1147 71.
9. Lesburg CA, Cable MB, Ferrari E, Hong Z, Mannarino AF, Weber PC. Crystal structure of the RNA-dependent RNA polymerase from hepatitis C virus reveals a fully encircled active site. Nat Struct Biol 1999 6 : 937 43.
10. Bressanelli S, Tomei L, Roussel A, et al. Crystal structure of the RNA-dependent RNA polymerase of hepatitis C virus. Proc Natl Acad Sci U S A 1999 96 : 13034 9.
11. Love RA, Parge HE, Wickersham JA, et al. The crystal structure of hepatitis C virus NS3 proteinase reveals a trypsin-like fold and a structural zinc binding site. Cell 1996 87 : 331 42.
12. Kim JL, Morgenstern KA, Lin C, et al. Crystal structure of the hepatitis C virus NS3 protease domain complexed with a synthetic NS4A cofactor peptide. Cell 1996 87 : 343 55.
13. Yan Y, Li Y, Munshi S, et al. Complex of NS3 protease and NS4A peptide of BK strain hepatitis C virus: a 2.2 A resolution structure in a hexagonal crystal form. Protein Sci 1998 7 : 837 47.
14. Lohmann V, Korner F, Koch J, Herian U, Theilmann L, Bartenschlager R. Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line. Science 1999 285 : 110 3.
15. Lohmann V, Korner F, Dobierzewska A, Bartenschlager R. Mutations in hepatitis C virus RNAs conferring cell culture adaptation. J Virol 2001 75 : 1437 49.
16. Blight KJ, Kolykhalov AA, Rice CM. Efficient initiation of HCV RNA replication in cell culture. Science 2000 290 : 1972 4.
17. Kato T, Date T, Miyamoto M, et al. Efficient replication of the genotype 2a hepatitis C virus subgenomic replicon. Gastroenterology 2003 125 : 1808 17.
18. De Francesco R, Carfi A. Advances in the development of new therapeutic agents targeting the NS3-4A serine protease or the NS5B RNA-dependent RNA polymerase of the hepatitis C virus. Adv Drug Deliv Rev 2007 59 : 1242 62.
19. Thimme R, Lohmann V, Weber F. A target on the move: innate and adaptive immune escape strategies of hepatitis C virus. Antiviral Res 2006 69 : 129 41.
20. Sumpter R Jr., Loo YM, Foy E, et al. Regulating intracellular antiviral defense and permissiveness to hepatitis C virus RNA replication through a cellular RNA helicase, RIG-I. J Virol 2005 79 : 2689 99.
21. Li K, Foy E, Ferreon JC, et al. Immune evasion by hepatitis C virus NS3/4A protease-mediated cleavage of the Toll-like receptor 3 adaptor protein TRIF. Proc Natl Acad Sci U S A 2005 102 : 2992 7.
22. Loo YM, Owen DM, Li K, et al. Viral and therapeutic control of IFN-beta promoter stimulator 1 during hepatitis C virus infection. Proc Natl Acad Sci U S A 2006 103 : 6001 6.
23. Lau DT, Fish PM, Sinha M, Owen DM, Lemon SM, Gale M Jr. Interferon regulatory factor-3 activation, hepatic interferon-stimulated gene expression, and immune cell infiltration in hepatitis C virus patients. Hepatology 2008 47 : 799 809.
24. Hinrichsen H, Benhamou Y, Wedemeyer H, et al. Short-term antiviral efficacy of BILN 2061, a hepatitis C virus serine protease inhibitor, in hepatitis C genotype 1 patients. Gastroenterology 2004 127 : 1347 55.
25. Lamarre D, Anderson PC, Bailey M, et al. An NS3 protease inhibitor with antiviral effects in humans infected with hepatitis C virus. Nature 2003 426 : 186 9.
26. Reiser M, Hinrichsen H, Benhamou Y, et al. Antiviral efficacy of NS3-serine protease inhibitor BILN-2061 in patients with chronic genotype 2 and 3 hepatitis C. Hepatology 2005 41 : 832 5.
27. Lin C, Lin K, Luong YP, et al. 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 2004 279 : 17508 14.
28. Lu L, Pilot-Matias TJ, Stewart KD, et al. Mutations conferring resistance to a potent hepatitis C virus serine protease inhibitor in vitro. Antimicrob Agents Chemother 2004 48 : 2260 6.
29. Reesink HW, Zeuzem S, Weegink CJ, et al. Rapid decline of viral RNA in hepatitis C patients treated with VX-950: a phase Ib, placebo-controlled, randomized study. Gastroenterology 2006 131 : 997 1002.
30. Sarrazin C, Kieffer TL, Bartels D, et al. Dynamic hepatitis C virus genotypic and phenotypic changes in patients treated with the protease inhibitor telaprevir. Gastroenterology 2007 132 : 1767 77.
31. Forestier N, Reesink HW, Weegink CJ, et al. Antiviral activity of telaprevir (VX-950) and peginterferon alfa-2a in patients with hepatitis C. Hepatology 2007 46 : 640 8.
32. McHutchison JG, Everson GT, Gordon SC, et al. PROVE1: results from a phase 2 study of telaprevir with peginterferon alfa-2a and ribavirin in treatment-naive subjects with hepatitis C. J Hepatol 2008 48 (Suppl. 2 S4 (4).
33. Zeuzem S, Hezode C, Ferenci P, et al. Telaprevir in combination with peginterferon-alfa-2a with or without ribavirin in the treatment of chronic hepatitis C: final results of the PROVE2 Study. Hepatology 2008 48 (Suppl. 1 418A (243).
34. Zeuzum S, Sarrazin C, Rouzier R, et al. Anti-viral activity of SCH 503034, a HCV protease inhibitor, administered as monotherapy in hepatitis C genotype-1 (HCV-1) patients refractory to pegylated interferon (peg-IFN-α). Hepatology 2005 42 (S1 A94.
35. Kwo P, Lawitz EJ, McCone J, et al. HCV SPRINT-1: Boceprevir plus Peginterferon alfa-2b/Ribavirin for Treatment of Genotype 1 Chronic Hepatitis C in Previously Untreated Patients. Hepatology 2008 48 (Suppl. 1 1027A.
36. Schiff E, Poordad F, Jacobson I, et al. Boceprevir (B) combination therapy in null responders (NR): response dependent on interferon responsiveness. J Hepatol 2008 48 (Suppl. 2 S46 (A104).
37. Sarrazin C, Rouzier R, Wagner F, et al. SCH 503034, a novel hepatitis C virus protease inhibitor, plus pegylated interferon alpha-2b for genotype 1 nonresponders. Gastroenterology 2007 132 : 1270 8.
38. Tong X, Bogen S, Chase R, et al. Characterization of resistance mutations against HCV ketoamide protease inhibitors. Antiviral Res 2008 77 : 177 85.
39. Van t Klooster GAE, Vanwelkenhuysen I, Hooijmaijers R, et al. Once-daily regimens of the HCV NS3/4A-protease inhibitor TMC435350 are predicted to provide therapeutic exposure in plasma and liver. J Hepatol 2008 2008 (Suppl. 2 S321 (A855).
40. Reesink H, Verloes R, Abou Farha K, et al. Safety of the HCV protease inhibitor TMC435350 in healthy volunteers and safety and activity in chronic hepatitis C infected individuals: a phase I study. J Hepatol 2008 2008 (Suppl. 2 S28 (A64).
41. Pottage JC, Lawitz E, Mazur D, Wyles D, Vargas H, et al. Short-term antiviral activity and safety of ACH-806 (GS-9132), an NS4A antagonist, in HCV genotype 1 infected individuals. J Hepatol 2008 46 (Suppl. 1 S294 (A783).
42. Watashi K, Ishii N, Hijikata M, et al. Cyclophilin B is a functional regulator of hepatitis C virus RNA polymerase. Mol Cell 2005 19 : 111 22.
43. Roberts SK, Cooksley G, Dore GJ, et al. Robust antiviral activity of R1626, a novel nucleoside analog: a randomized, placebo-controlled study in patients with chronic hepatitis C. Hepatology 2008 48 : 398 406.
44. Pockros PJ, Nelson D, Godofsky E, et al. R1626 plus peginterferon Alfa-2a provides potent suppression of hepatitis C virus RNA and significant antiviral synergy in combination with ribavirin. Hepatology 2008 48 : 385 97.
45. Pockros P, Nelson D, Godofsky E, et al. High relapse rate seen at week 72 for patients treated with R1626 combination therapy. Hepatology 2008 48 : 1349 50.
46. Le Pogam S, Jiang WR, Leveque V, et al. In vitro selected Con1 subgenomic replicons resistant to 2′-C-methyl-cytidine or to R1479 show lack of cross resistance. Virol 2006 351 : 349 59.
47. Le Pogam S, Seshaadri A, Kosaka A, et al. Existence of hepatitis C virus NS5B variants naturally resistant to non-nucleoside, but not to nucleoside, polymerase inhibitors among untreated patients. J Antimicrob Chemother 2008 61 : 1205 16.
48. Le Pogam S, Seshaadri A, Kang H, et al. Low level of resistance, low viral fitness and absence of resistance mutations in baseline quasispecies may contribute to high barrier to R1626 resistance in vivo. J Hepatol 2008 48 (Suppl. 2 S10 (A21).
49. Nelson D, Pockros PJ, Godofsky E, et al. High end-of-treatment response (84%) after 4 weeks of R1626, peginterferon alfa-2a (40kd) and ribavirin followed by a further 44 weeks of peginterferon alfa-2a and ribavirin. J Hepatol 2008 48 (Suppl. 2 S371 (993).
50. Reddy R, Rodrigues-Torres M, Gane E, et al. Antiviral activity, pharmacokinetics, safety, and tolerability of R7128, a novel nucleoside HCV RNA polymerase inhibitor, following multiple, ascending, oral doses in patients with HCV genotype 1 infection who have failed prior interferon therapy. Hepatology 2008 46 (Suppl. 1 LB9.
51. Lalezari J, Gane E, Rodriguez-Torres M, et al. Potent antiviral activity of the HCV nucleoside polymerase inhibitor R7128 with PEG-IFN and ribavirin: interim results of R7128 500 mg bid for 28 days. J Hepatol 2008 48 (Suppl. 2 S29 (A66).
52. Standring D, Lanford R, Cretton-Scott E, et al. Potent antiviral activity of 2nd generation HCV nucleotide inhibitors, IDX102 and IDX184, in HCV-infected chimpanzees. J Hepatol 2008 48 (Suppl. 2 S30 (A67).
53. Olsen DB, Davies M, Handt L, et al. The nucleoside inhibitor MK-0608 mediates suppression of HCV replication for >30 days in chronically infected chimpanzees. Proceedings of the 46th Interscience Conference on Antimicrobial Agents and Chemotherapy, 2006: Abstract V-1914a.
54. Chandra P, Raible D, Harper D, et al. 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 2006 130 (Suppl. 2 A748.
55. Villano SA, Raible D, Harper D, et al. Antiviral activity of the non-nucleoside polymerase inhibitor, HCV-769, in combination with pegylated interferon alpha-2b in treatment-naive patients with chronic HCV. J Hepatol 2007 46 (Suppl.1 S24 (A50).
56. Cooper C, Lawitz EJ, Ghali P, et al. Antiviral activity of the non-nucleoside polymerase inhibitor, VCH-759, in chronic Hepatitis C patients:Results from a randomized, double-blind, placebo -controlled, ascending multiple dose study. Hepatology 2007 46 (Suppl. 1 LB11.
57. Nicolas O, Boivin I, St-Denis C, Bedard J. Genotypic analysis of HCV NS5B variants selected from patients treated with VCH-759. J Hepatol 2008 48 (Suppl. 2 S317 (A844).
58. Bavisotto L, Wang CC, Jacobson IM, et al. Antiviral, pharmacokinetic and safety data for GS-9190, a non-nucleoside HCV NS5b polymerase inhibitor, in a phase-1 trial in HCV genotype 1 infected subjects. Hepatology 2007 46 (Suppl. 1 A49.
59. Chen CM, He Y, Lu L, et al. Activity of a potent hepatitis C virus polymerase inhibitor in the chimpanzee model. Antimicrob Agents Chemother 2007 51 : 4290 6.
60. Ma S, Boerner JE, TiongYip C, et al. NIM811, a cyclophilin inhibitor, exhibits potent in vitro activity against hepatitis C virus alone or in combination with alpha interferon. Antimicrob Agents Chemother 2006 50 : 2976 82.
61. Nakagawa M, Sakamoto N, Tanabe Y, et al. Suppression of hepatitis C virus replication by cyclosporin a is mediated by blockade of cyclophilins. Gastroenterology 2005 129 : 1031 41.
62. Flisiak R, Horban A, Kierkus J, et al. The cyclophilin inhibitor DEBIO-025 has a potent dual anti-HIV and anti-HCV activity in treatment-naive HIV/HCV co-infected subjects. Hepatology 2006 44 (Suppl. 1 A1130.
63. Flisiak R, Feinman SV, Jablowski M, et al. Efficacy and safety of increasing doses of the cyclophilin inhibitor DEBIO 025 in combination with pegylated interferon alpha-2a in treatment naive chronic HCV patients. J Hepatol 2008 48 (Suppl. 1 S62 (A143).
64. Robida JM, Nelson HB, Liu Z, Tang H. Characterization of hepatitis C virus subgenomic replicon resistance to cyclosporine in vitro. J Virol 2007 81 : 5829 40.
65. Yang F, Robotham JM, Nelson HB, Irsigler A, Kenworthy R, Tang H. Cyclophilin A is an essential cofactor for hepatitis C virus infection and the principal mediator of cyclosporine resistance in vitro. J Virol 2008 82 : 5269 78.
66. Goto K, Watashi K, Murata T, Hishiki T, Hijikata M, Shimotohno K. Evaluation of the anti-hepatitis C virus effects of cyclophilin inhibitors, cyclosporin A, and NIM811. Biochem Biophys Res Commun 2006 343 : 879 84.
67. Whitby K, Taylor D, Patel D, Ahmed P, Tyms AS. Action of celgosivir (6 O-butanoyl castanospermine) against the pestivirus BVDV: implications for the treatment of hepatitis C. Antivir Chem Chemother 2004 15 : 141 51.
68. Yoshida E, Kunimoto D, Lee SS, et al. Results of a phase 2 dose ranging study of orally administered celgosivir as monotherapy in chronic hepatitis C genotype 1 patients. Gastroenterology 2006 130 : A784.
69. Kaita K, Yoshida E, Kunimoto D, et al. Ph II proof of concept study of celgosivir in combination with peginterferon alfa-2b and ribavirin in chronic hepatitis C genotype 1 non-responder patients. J Hepatol 2007 46 (Suppl. 1 S56 (A127).
70. Liu C, Zhu H, Subramanian GM, Moore PA, Xu Y, Nelson DR. Anti-hepatitis C virus activity of albinterferon alfa-2b in cell culture. Hepatol Res 2007 37 : 941 7.
71. Bain VG, Kaita KD, Yoshida EM, 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 2006 44 : 671 8.
72. Balan V, Nelson DR, Sulkowski MS, 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 2006 11 : 35 45.
73. Zeuzem S, Yoshida EM, Benhamou Y, et al. Albinterferon alfa-2b dosed every two or four weeks in interferon-naive patients with genotype 1 chronic hepatitis C. Hepatology 2008 48 : 407 17.
74. Bain VG, Kaita KD, Marotta P, et al. Safety and antiviral activity of albinterferon alfa-2b dosed every four weeks in genotype 2/3 chronic hepatitis C patients. Clin Gastroenterol Hepatol 2008 6 : 701 6.
75. Subramanian GM, Fiscella M, Lamouse-Smith A, Zeuzem S, McHutchison JG. Albinterferon alpha-2b: a genetic fusion protein for the treatment of chronic hepatitis C. Nat Biotechnol 2007 25 : 1411 9.
76. Dzyublyk I, Yegorova T, Moroz L, et al. Phase 2a study to evaluate the safety and tolerability and anti-viral of 4 doses of a novel, controlled-release interferon alfa-2b (Locteron) given every 2 weeks for 12 weeks in treatment-naive patients with chronic hepatitis C (genotype 1). Hepatology 2007 46 (Suppl. 1 LB10.
77. Benhamou Y, Pockros P, Rodriquez-Torres M, et al. The safety and efficacy of viramidine plus pegIFN alfa-2b versus ribavirin plus pegIFN alfa-2b in therapy-naive patients infected with HCV: phase 3 results (VISER1). J Hepatol 2006 44 (Suppl. 2 A751.
78. Marcellin P, Lurie Y, RodriguesTorres M, et al. The safety and efficacy of taribavirin plus pegylated interferon alfa2a versus ribavirin plus pegylated interferon alfa2a in therapy naive patients infected with HCV: phase 3 results. J Hepatol 2007 46 (Suppl. 1 S7 (A10).
79. Poordad F, Lawitz E, Chun E, et al. Treatment week 12 results of weight-based taribavirin versus weight-based ribavirin, both with peginterferon alfa-2b, in naive chronic hepatitis c, genotype 1 patients. J Hepatol 2008 48 (Suppl. 2 S373 (A996).
80. Korba BE, Montero AB, Farrar K, et al. Nitazoxanide, tizoxanide and other thiazolides are potent inhibitors of hepatitis B virus and hepatitis C virus replication. Antiviral Res 2008 77 : 56 63.
81. Rossignol JF, Kabil SM, El-Gohary Y, Elfert A, Keeffe EB. Clinical trial: randomized, double-blind, placebo-controlled study of nitazoxanide monotherapy for the treatment of patients with chronic hepatitis C genotype 4. Aliment Pharmacol Ther 2008 28 : 574 80.
82. Schiff ER, Everson GT, Tsai N, et al. HCV-specific cellular immunity, RNA reductions, and normalization of ALT in chronic HCV subjects after treatment with GI-5005, a yeast-based immunotherapy targeting NS3 and core: a randomized, double-blind, placebo-controlled phase 1b study. Hepatology 2007 46 (Suppl. 1 A1304.
83. Kuzushita N, Gregory SH, Monti NA, Carlson R, Gehring S, Wands JR. Vaccination with protein-transduced dendritic cells elicits a sustained response to hepatitis C viral antigens. Gastroenterology 2006 130 : 453 64.
84. Jones KL, Brown LE, Eriksson EM, et al. Human dendritic cells pulsed with specific lipopeptides stimulate autologous antigen-specific T cells without the addition of exogenous maturation factors. J Viral Hepat 2008 15 : 761 72.
85. Wang C, Gale M Jr., Keller BC, et al. Identification of FBL2 as a geranylgeranylated cellular protein required for hepatitis C virus RNA replication. Mol Cell 2005 18 : 425 34.
86. Ye J, Wang C, Sumpter R Jr., Brown MS, Goldstein JL, Gale M Jr. Disruption of hepatitis C virus RNA replication through inhibition of host protein geranylgeranylation. Proc Natl Acad Sci U S A 2003 100 : 15865 70.
87. Ikeda M, Abe K, Yamada M, Dansako H, Naka K, Kato N. Different anti-HCV profiles of statins and their potential for combination therapy with interferon. Hepatology 2006 44 : 117 25.
88. O'Leary JG, Chan JL, McMahon CM, Chung RT. Atorvastatin does not exhibit antiviral activity against HCV at conventional doses: a pilot clinical trial. Hepatology 2007 45 : 895 8.
89. O'George J, Kenedi C, McHutchison J, et al. A pilot study to assess the impact of rosuvastatin therapy on HCV RNA and lipid fractions in chronic hepatitis C patients. Gastroenterology 2007 132 (Suppl.1 S741.
90. Bader T, Fazili J, Madhoun M, et al. Fluvastatin inhibits hepatitis C replication in humans. Am J Gastroenterol 2008 103 : 1383 9.
91. Shan Y, Zheng J, Lambrecht RW, Bonkovsky HL. Reciprocal effects of micro-RNA-122 on expression of heme oxygenase-1 and hepatitis C virus genes in human hepatocytes. Gastroenterology 2007 133 : 1166 74.
92. Randall G, Panis M, Cooper JD, et al. Cellular cofactors affecting hepatitis C virus infection and replication. Proc Natl Acad Sci U S A 2007 104 : 12884 9.
93. Pedersen IM, Cheng G, Wieland S, et al. Interferon modulation of cellular microRNAs as an antiviral mechanism. Nature 2007 449 : 919 22.
94. Jopling CL, Yi M, Lancaster AM, Lemon SM, Sarnow P. Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA. Science 2005 309 : 1577 81.
95. Kwo P, Lawitz E, McCone J, et al. Interim results from HCV SPRINT-1: RVR/EVR from phase 2 study of boceprevir plus Pegintron (peginterferon alfa-2b)/ribavirin in treatment-naive subjects with genotype-1 CHC. J Hepatol 2008 48 (Suppl. 2 S372 (A995).
96. Pockros P, Nelson D, Godofsky E, et al. Robust synergistic antiviral effect of R1626 in combination with peginterferon alfa-2a (40KD), with or without ribavirin: interim analysis results of phase 2a study. Hepatology 2007 46 : 311A (167).