Current and future treatment options for HCV

Annals of Hepatology

Volumn 8, Issue 2, 2009, Pages 103-112

  Kronenberger, Bernd ^a   Zeuzem, Stefan ^a  

^a UNIVERSITY HOSPITAL FRANKFURT   (Germany)

Author keywords

Hepatitis C; Peginterferon; Polymerase inhibitors; Protease inhibitors; Ribavirin; STAT C

Indexed keywords

4' AZIDOCYTIDINE; 4' AZIDOCYTIDINE 2',3',5' TRIISOBUTYRATE; ALBINTERFERON ALPHA2B; ALPHA INTERFERON; BENZIMIDAZOLE; BI 201335; BOCEPREVIR; COLCHICINE; IDX 184; ITNM 191; LOCTERON; MK 7009; NITAZOXANIDE; NUCLEOTIDE DERIVATIVE; PEGINTERFERON; PEGINTERFERON ALPHA2A; PEGINTERFERON ALPHA2B; PEGINTERFERON LAMBDA; PLACEBO; PROTEINASE INHIBITOR; R 7128; RIBAVIRIN; RITONAVIR; RNA DIRECTED DNA POLYMERASE INHIBITOR; SCH 900518; SILIBININ; TELAPREVIR; TMC 435; UNCLASSIFIED DRUG; UNINDEXED DRUG; VALOPICITABINE;

ANTIVIRAL ACTIVITY; ANTIVIRAL THERAPY; CLINICAL TRIAL; DRUG EFFICACY; DRUG MECHANISM; DRUG RESPONSE; DRUG TOLERABILITY; FLU LIKE SYNDROME; GASTROINTESTINAL SYMPTOM; GENOTYPE; HEMATOLOGIC DISEASE; HEPATITIS C; HEPATITIS C VIRUS; HUMAN; LOW DRUG DOSE; NONHUMAN; PATIENT CARE; PATIENT COMPLIANCE; REVIEW; VIRUS LOAD; VIRUS MUTATION;

EID: 67650526658     PISSN: 16652681     EISSN: None     Source Type: Journal    
DOI: 10.1016/s1665-2681(19)31786-7     Document Type: Review

References (56)

1. Hadziyannis SJ, Sette H Jr., Morgan TR, 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 2004; 140(5): 346-355. (Pubitemid 38268915)
2. Zeuzem S, Buti M, Ferenci P, Sperl J, Horsmans Y, Cianciara J, et al. 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 2006; 44(1): 97-103. (Pubitemid 41772522)
3. 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 2005; 129(2): 522-527. (Pubitemid 41096640)
4. Mangia A, Santoro R, Minerva N, Ricci GL, 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 2005; 352(25): 2609-2617. (Pubitemid 41007847)
5. Shiffman ML, Suter F, Bacon BR, Nelson D, Harley H, Sola R, et al. Peginterferon alfa-2a and ribavirin for 16 or 24 weeks in HCV genotype 2 or 3. N Engl J Med 2007; 357(2): 124-134. (Pubitemid 47057730)
6. Zeuzem S, Hultcrantz R, Bourliere M, Goeser T, Marcellin P, Sanchez-Tapias J, et al. Peginterferon alfa-2b plus ribavirin for treatment of chronic hepatitis C in previously untreated patients infected with HCV genotypes 2 or 3. J Hepatol 2004; 40(6): 993-999. (Pubitemid 38670134)
7. 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 2006; 130(4): 1086-1097.
8. Buti M, Lurie Y, Zakharova N, Blokhina NP, Horban A, Sarrazin C, et al. Extended treatment duration in chronic hepatitis C genotype 1 infected slow responders: final results of the SUCCESS study. J Hepatol 2009; 50S: 58.
9. Di Bisceglie AM, Shiffman ML, Everson GT, Lindsay KL, Everhart JE, Wright EC, et al. Prolonged therapy of advanced chronic hepatitis C with low-dose peginterferon. N Engl J Med 2008; 359(23): 2429-2441.
10. Afdhal N, Levine R, Brown R, Freilich B, O'Brian M, Brass C. Colchicine versus peginterferon alfa-2b long term therapy: Results of the 4-year CoPilot trial. J Hepatol 2008; 48S: 4.
11. Bruix J, Poynard T, Colombo M, Schiff E, Reichen J, Burak K, et al. Pegintron maintenance therapy in cirrhotic (Metavir F4) HCV patients, who failed to respond to interferon/ribavirin therapy: Final results of the EPIC3 cirrhosis maintenance trial. J Hepatol 2009; 50S: 22.
12. Zeuzem S, Sulkowski M, Lawitz E, Rustgi V, Lurie Y, Grigorescu M, et al. Efficacy and safety of albinterferon alfa-2b in combination with ribavirin in treatment-naive, chronic hepatitis c genotype 1 patients. J Hepatol 2009; 50S: 377.
13. Nelson D, Benhamou Y, Chuang WL, Lawitz E, Flisiak R, Rodriguez-Torres M, et al. Efficacy and safety results od albinterferon alfa-2b in combination with ribavirin in interferon alfa treatment naive patients with genotype 2 or 3 chronic hepatitis. J Hepatol 2009; 50S: 378.
14. Lawitz E, Younossi ZM, Shiffman ML, Gordon S, Ghalib RH, Long W, et al. Randomized trial comparing systemic and local reactions to controlled-release interferon alfa-2b and pegylated interferon alfa-2b in hepatitis C patients who failed prior treatment. J Hepatol 2009: 50S(231).
15. Shiffman ML, Lawitz E, Zaman A, Vierling J, Yoffe B, Freeman J, et al. Peg-IFN-1: Antiviral activity and safety profile in a 4-week phase 1b study in relapsed genotype 1 hepatitis C infection. J Hepatol 2009; 50S: 237.
16. Meylan E, Curran J, Hofmann K, Moradpour D, Binder M, Bartenschlager R, et al. Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus. Nature 2005; 437(7062): 1167-1172. (Pubitemid 41509355)
17. Li K, Foy E, Ferreon JC, Nakamura M, Ferreon AC, Ikeda M, 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 USA 2005; 102(8): 2992-2997. (Pubitemid 40299904)
18. Hezode C, Forestier N, Dusheiko G, Ferenci P, Pol S, Goeser T, et al. Telaprevir and peginterferon with or without ribavirin for chronic HCV infection. N Engl J Med 2009; 360(18): 1839-1850.
19. McHutchison JG, Everson GT, Gordon SC, Jacobson IM, Sulkowski M, Kauffman R, et al. Telaprevir with peginterferon and ribavirin for chronic HCV genotype 1 infection. N Engl J Med 2009; 360(18): 1827-1838.
20. Manns MP, Muir A, Adda N, Jacobson I, Afdhal N, Heathcote EJL, et al. Telaprevir in hepatitis C genotype 1 infected patients with prior non-response, viral breakthrough or relapse to peginterferon-alfa-2a/b and ribavirin therapy: SVR results of the PROVE3 study. J Hepatol 2009; 50S: 379.
21. Malcolm BA, 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 2006; 50(3): 1013-1020. (Pubitemid 43327807)
22. Susser S, Welker M, Zettler M, Wohnsland A, Hughes E, Ralston R, et al. Clonal analysis of mutations selected in the HCV NS3 protease domain of genotype 1 non-responders treated with boceprevir. J Hepatol 2008; 48: 29A.
23. Kwo PY, Lawitz E, McCone J, Schiff E, Vierling J, Pound D et al. HCV SPRINT-1 final results: SVR 24 from a phase 2 study of boceprevir plus peginterferon alfa-2b/ribavirin in treatment naive subjects with genotype 1 chronic hepatitis C. J Hepatol 2009; 50S: 4.
24. Forestier N, Larrey D, Marcellin P, Benhamou Y, Guyader D, Bradford W, et al. Antiviral activity and safety of ITMN-191 in combination with peginterferon alfa-2a and ribavirin in patients with chronic hepatitis C virus. J Hepatol 2009; 50S: 35.
25. Reesink H, Bergmann J, de Bruijne J, Weegink C, van Lier J, van Vliet A, et al. Safety and antiviral activity of SCH 900518 administered as monotherapy and in combination with peginterferon alfa-2b to naive and treatment experienced HCV-1 infected patients. J Hepatol 2009; 50S: 35.
26. Manns MP, Reesink H, Moreno C, Berg T, Benhamou Y, Horsmans Y, et al. OPERA-1 trial: Interim analysis of safety and antiviral activity of TMC435 in treatment-naive genotype 1 HCV patients. J Hepatol 2009; 50S: 7.
27. Kukolj G, Benhamou Y, Manns MP, Bourliere M, Pol S, Schuchmann M, et al. BI 201335, a potent HCV NS3 protease inhibitor in treatment naive and -experienced chronic HCV genotype infection: Genotypic and phenotypic analysis of the NS3 protease domain. J Hepatol 2009; (50S): 347.
28. Manns MP, Bourliere M, Benhamou Y, Pol S, Bonacini M, Berg T, et al. Safety and antiviral activity of BI201335, a new HCV NS protease inhibitor, in treatment naive patients with chronic hepatitis C genotype 1 infection given as monotherapy and in combination with peginterferon alfa 2a and ribavirin. Hepatology 2008; 48: 1133.
29. Manns MP, Bourliere M, Benhamou Y, Schuchmann M, Haussinger D, Pol S, et al. Safety and antiviral activity of BI201335, a new HCV NS3 protease inhibitor, in combination therapy with peginterferon alfa 2a and ribavirin for 28 days in treatment experienced patients with chronic hepatitis C genotype 1 infection. Hepatology 2008; 48: 1151.
30. Manns MP, Gane E, Rodriguez-Torres M, Stoehr A, Yeh CT, Wiedmann R, et al. MK-7009 significantly improves rapid viral response in combination with peginterferon alfa-2a and ribavirin in patients with chronic hepatitis C genotype 1 infection. J Hepatol 2009; 50S: 384.
31. Lawitz E, Nguyen T, Younes Z, Santoro J, Gitlin N, McEniry D, et al. Clearance of HCV RNA with valopicitabine (NM283) plus peg-interferon in treatment-naive patients with HCV-1 infection: results at 24 and 48 weeks. Journal of Hepatology 2007; 46: 9A.
32. Klumpp K, Leveque V, Le Pogam S, Ma H, Jiang WR, Kang H, et al. The novel nucleoside analog R1479 (4′-azidocytidine) is a potent inhibitor of NS5B-dependent RNA synthesis and hepatitis C virus replication in cell culture. J Biol Chem 2006; 281(7): 3793-3799. (Pubitemid 43847803)
33. Roberts S, Cooksley G, Dore G, Robson R, Shaw D, Berns H, et al. Results from a phase 1B, multiple dose study of R1626, a novel nucleoside analog targeting HCV polymerase in chronic HCV genotype 1 patients. Hepatology 2006; 44: 692A.
34. Nelson D, Pockros PJ, Godofsky E, Rodriguez-Torres M, Everson G, Fried M, et al. High end-of-treatment response (84%) after 4 weeks of R1626, peginterferon alfa-2a and ribavirin followed by a further 44 weeks of peginterferon alfa-2a and ribavirin. J Hepatol 2008; 48: 371A.
35. Lalezari J, Gane E, Rodriguez-Torres M, DeJesus E, Nelson D, Everson G, et al. Potent antiviral activity of the HCV nucleotiside polymerase inhibitor R7128 with PEG-IFN and ribavirin: Interim results of R7128 500 mg BID for 28 days. J Hepatol 2008; 48: 29A.
36. Gane E, Rodriguez-Torres M, Nelson D, Jacobson IM, McHutchison J, Jeffers L, et al. Antiviral activity of the HCV nucleoside polymerase inhibitor R7128 in HCV Genotype 2 and 3 prior non-responders: Interim results of R7128 1,500 mg BID With PEG-IFN and ribavirin for 28 days. Hepatology 2008.
37. Le Pogam S, Seshaadri A, Kosaka A, Hu S, Beard A, Julian S, et al. No evidence of R7128 drug resistance after op to 4 weeks treatment of GT 1, 2 and 3 hepatitis C virus infected individuals. J Hepatol 2009; 50S: 348.
38. Zhou XJ, Pietropaolo K, Sullivan-Bolyai J, Kuca B, Liu W, Xu L, et al. IDX, a liver targeted nucleotide HCV polymerase inhibitor: Results from a first in man safety and pharmacokinetic study. J Hepatol 2009; 50: 351.
39. Villano S, Raible D, Harper D, Speth J, Chandra P, Shaw D, et al. Antiviral activity of the non-nucleoside polymerase inhibitor, HCV- 796, in combination with pegylated interferon alfa-2b in treatment naive patients with chronic HCV. J Hepatol 2007; 46: 24A.
40. Jacobson I, Pockros P, Lalezari J, Lawitz E, Rodriguez-Torres M, DeJesus E, et al. Antiviral activity of filibuvir in combination with pegylated interferon alfa-2a and ribavirin for 28 days in treatment naive patients chronically infected with HCV genotype 1. J Hepatol 2009; 50S: 382.
41. Lawitz E, Cooper C, Rodriguez-Torres M, Ghalib RH, Lalonde R, Sheikh A, et al. Safety, tolerability and antiviral activity of VCH-916, a novel non-nucleoside HCV polymerase inhibitor in patients with chronic HCV genotype 1 infection. J Hepatol 2009; 50S: 37.
42. Nicolas O, Boivin I, Berneche-D'Amours A, Fex P, Denis F, Selliah S, et al. Genotypic and phenotypic analysis of HCV NS5B variants selected from patients treated with VCH-916. J Hepatol 2009; 50S: 349.
43. Lawitz E, Rodriguez-Torres M, DeMicco M, Nguyen T, Godofsky E, Appleman J, et al. Antiviral activity of ANA598, a potent nonnucleoside polymerase inhibitor, in chronic hepatitis C patients. J Hepatol 2009; 50S: 384.
44. Cooper C, Larouche R, Bourgault B, Chauret N, Proulx L. Safety, tolerability and pharmacokinetics of the HCV polymerase inhibitor VCH-222 following single dose administration in healthy volunteers and antiviral activity in HCV infected individuals. J Hepatol 2009; 50S: 342.
45. Brainard D, Wright DH, Sneddon K, Cummings C, Sun P, Valentine J, et al. Safety, tolerability, and pharmacokinetics after single and multiple doses of MK3281 in healthy subjects. J Hepatol 2009; 50S: 341.
46. Gane E, Roberts S, Stedman C, Angus PW, Ritchie B, Elston R, et al. First in-man demonstration of potent antiviral activity with a nucleoside polymerase (R7128) and protease (R7227/ITMN-191) inhibitor combination in HCV: Safety, pharmacokinetics, and virologic results from INFORM-1. J Hepatol 2009; 50S: 1046.
47. Blair BM, Broering TJ, Babcock GJ, Szabo G, Finberg RW, Cheslock PS, et al. A novel human monoclonal antibody directed against the E2 glycoprotein of HCV prevents infection in chimpanzees. J Hepatol 2009; 50: 381.
48. de Bruijne J, Bergmann J, Weegink C, van Nieuwkerk K, de Knegt R, van de Wetering de Rooij J, et al. JTK-652 is a novel HCV entry inhibitor: Results of a phase 1 study evaluating safety, tolerability and antiviral activity in chronic hepatitis C patients. J Hepatol 2009; 50S: 342.
49. Flisiak R, Horban A, Kierkus J, Stanczak J, Cielnak I, Stanczak P, et al. The cyclophilin inhibitor DEBIO-025 has a potent dual anti-HIV and anti-HCV activity in treatment-naïve HIV/HCV coinfected subjects. Hepatology 2006; 44: 609A.
50. Nelson DR, Ghalib RH, Sulkowski M, Schiff E, Rustgi V, Pockros PJ, et al. Efficacy and safety of the cyclophilin inhibitor DEBIO 025 in combination with peginterferon alfa-2a and ribavirin in previously null responder genotype 1 HCV patients. J Hepatol 2009; 50S: 40.
51. Lawitz E, Rouzier R, Nguyen T, Huang D, Ke J, Praestgaard J, et al. Safety and antiviral efficacy of 14 days of the cyclophilin inhibitor NIM811 in combination with peginterferon alfa-2a in relapsed genotype 1 HCV infected patients. J Hepatol 2009; 50S: 379.
52. Hopkins S, Heuman D, Gavis E, Lalezari J, Glutzer E, DiMassimo B, et al. Safety, plasma pharmacokinetics, and anti-viral activity of SCY-635 in adult patients with chronic hepatitis C virus infection. J Hepatol 2009; 50S: 36.
53. Ferenci P, Scherzer TM, Kerschner H, Rutter K, Beinhardt S, Hofer H, et al. Silibinin is a potent antiviral agent in patients with chronic hepatitis C not responding to pegylated interferon/ribavirin therapy. Gastroenterology 2008; 135(5): 1561-1567.
54. Rutter K, Beinhardt S, Kerschner H, Scherzer TM, Hofer H, Popow-Kraupp T, et al. Intravenous silibinin as "rescue treatment" for on treatment nonresponders to full dose of peginterferon/ribavirin combination therapy. J Hepatol 2009; 50S: 235.
55. Rossignol JF, Elfert A, El-Gohary Y, Keefe EB. Randomized controlled trial of nitazoxanide peginterferon ribavirin, nitazoxanide peginterferon, and peginterferon ribavirin in the treatment of patients with chronic hepatitis C genotype 4. J Hepatol 2008; 48: 30.
56. Bacon B, Shiffman ML. Phase 2 randomized, double-blind, placebo- controlled study of nitazoxanide plus peginterferon and ribavirin in HCV genotype 1 patients: Interim analysis shows increase in EVR. J Hepatol 2009; 50S: 381.