The era of direct-acting antivirals: The evolving role of interferon and ribavirin for the treatment of chronic hepatitis C

Clinical Medicine Insights: Therapeutics

Volumn 4, Issue , 2012, Pages 39-56

  Gaetano, John N ^a   Desai, Archita P ^a   Reau, Nancy ^a  

^a UNIVERSITY OF CHICAGO MEDICAL CENTER   (United States)

Author keywords

Boceprevir; Chronic hepatitis C; Direct acting antivirals; Interferon; Non nucleoside inhibitors; NS5A inhibitors; NS5B polymerase inhibitors; Nucleoside inhibitors; Protease inhibitor; Ribavirin; Telaprevir

Indexed keywords

ALFUZOSIN; ALPHA INTERFERON; ALPHA2A INTERFERON; ALPHA2B INTERFERON; ANTICONVULSIVE AGENT; BALAPIRAVIR; BENZODIAZEPINE DERIVATIVE; BETA INTERFERON; BOCEPREVIR; COLCHICINE; DANOPREVIR; ELTROMBOPAG; EPLERENONE; ERGOT DERIVATIVE; ERYTHROPOIETIN; FILIBUVIR; GRANULOCYTE COLONY STIMULATING FACTOR; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; PEGINTERFERON ALPHA; PEGINTERFERON ALPHA2A; PEGINTERFERON ALPHA2B; PLACEBO; PROTEINASE INHIBITOR; RIBAVIRIN; RNA DIRECTED DNA POLYMERASE INHIBITOR; SEROTONIN UPTAKE INHIBITOR; SIMEPREVIR; TELAPREVIR; UNINDEXED DRUG; VALOPICITABINE;

ANEMIA; ANTIVIRAL RESISTANCE; ANUS PRURITUS; ARTHRALGIA; AUTOIMMUNE DISEASE; BONE MARROW SUPPRESSION; CARDIOVASCULAR DISEASE; CHILL; COMBINATION CHEMOTHERAPY; DEPRESSION; DIARRHEA; DISTRIBUTION VOLUME; DRESS SYNDROME; DRUG CLEARANCE; DRUG DOSE COMPARISON; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG ERUPTION; DRUG FEVER; DRUG HALF LIFE; DRUG INDUCED HEADACHE; DRUG MECHANISM; DRUG METABOLISM; DRUG RESPONSE; DRUG SAFETY; DRUG TREATMENT FAILURE; DRUG WITHDRAWAL; DYSGEUSIA; ECZEMA; FATIGUE; FLU LIKE SYNDROME; GASTROINTESTINAL SYMPTOM; GENE; GENETIC VARIABILITY; GENOTYPE; GRAVES DISEASE; HASHIMOTO DISEASE; HEMOLYSIS; HEPATITIS C; HUMAN; IL2B GENE; LIVER CIRRHOSIS; LIVER FIBROSIS; LYMPHOCYTOPENIA; MAXIMUM PLASMA CONCENTRATION; MENTAL DISEASE; MIXED INFECTION; MYALGIA; NAUSEA; NEUROLOGIC DISEASE; NEUTROPENIA; NONHUMAN; PATIENT PREFERENCE; PRURITUS; RECOMMENDED DRUG DOSE; RELAPSE; REVIEW; SARCOIDOSIS; SIDE EFFECT; SKIN DISEASE; STEVENS JOHNSON SYNDROME; SUSTAINED VIROLOGIC RESPONSE; THROMBOCYTOPENIA; THYROID DISEASE; TIME TO MAXIMUM PLASMA CONCENTRATION; TREATMENT RESPONSE; UNSPECIFIED SIDE EFFECT; VACCINATION; VIRAL CLEARANCE; VIRUS LOAD; VISUAL IMPAIRMENT; VOMITING;

EID: 84859715484     PISSN: 1179559X     EISSN: 1179559X     Source Type: Journal    
DOI: 10.4137/CMT.S6792     Document Type: Review

References (84)

1. Holmberg S, et al. The growing burden of mortality associated with viral hepatitis in the United States, 1999-2007. Hepatology. 2011;54(S1):483A.
2. Shepard CW, Finelli L, Alter MJ. Global epidemiology of hepatitis C virus infection. Lancet Infect Dis. 2005;5(9):558-67.
3. Desai AP, Reau N. Naives, nonresponders, relapsers: who is there left to treat? Clin Liver Dis. 2011;15(3):483-95.
4. Davis GL, et al. Aging of hepatitis C virus (HCV)-infected persons in the United States: a multiple cohort model of HCV prevalence and disease progression. Gastroenterology. 2010;138(2):513-21,521. e1-6.
5. Hoofnagle JH, et al. Treatment of chronic non-A, non-B hepatitis with recombinant human alpha interferon. A preliminary report. N Engl J Med. 1986;315(25):1575-8.
6. Davis GL, et al. Treatment of chronic hepatitis C with recombinant interferon alfa. A multicenter randomized, controlled trial. Hepatitis Interventional Therapy Group. N Engl J Med. 1989;321(22):1501-6.
7. Ghany MG, et al. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology. 2009;49(4):1335-74.
8. Buti M, Esteban R. 1990-2010: two decades of interferon-based therapy. Clin Liver Dis. 2011;15(3):473-82.
9. Choo QL, et al. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science. 1989;244(4902):359-62.
10. Yoshioka K, et al. Detection of hepatitis C virus by polymerase chain reaction and response to interferon-alpha therapy: relationship to genotypes of hepatitis C virus. Hepatology. 1992;16(2):293-9.
11. Kanai K, Kako M, Okamoto H. HCV genotypes in chronic hepatitis C and response to interferon. Lancet. 1992;339(8808):1543.
12. Okada S, et al. The degree of variability in the amino terminal region of the E2/NS1 protein of hepatitis C virus correlates with responsiveness to interferon therapy in viremic patients. Hepatology. 1992;16(3):619-24.
13. Poynard T, et al. Randomised trial of interferon alpha2b plus ribavirin for 48 weeks or for 24 weeks versus interferon alpha2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus. International Hepatitis Interventional Therapy Group (IHIT). Lancet. 1998;352(9138):1426-32.
14. McHutchison JG, et al. Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. Hepatitis Interventional Therapy Group. N Engl J Med. 1998;339(21):1485-92.
15. Glue P, et al. Pegylated interferon-alpha2b: pharmacokinetics, pharmacodynamics, safety, and preliminary efficacy data. Hepatitis C Intervention Therapy Group. Clin Pharmacol Ther. 2000;68(5):556-67.
16. Manns MP, 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(9286):958-65.
17. Hadziyannis SJ, 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):346-55.
18. Fried MW, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis Cvirus infection. N Engl J Med. 2002;347(13):975-82.
19. Aronsohn A, Reau N. Long-term outcomes after treatment with interferon and ribavirin in HCV patients. J Clin Gastroenterol. 2009;43(7):661-71.
20. Platanias LC. Mechanisms of type-I- and type-II-interferon-mediated signalling. Nat Rev Immunol. 2005;5(5):375-86.
21. Ferenci P, et al. Predicting sustained virological responses in chronic hepatitis C patients treated with peginterferon alfa-2a (40 KD)/ribavirin. J Hepatol. 2005;43(3):425-33.
22. McHutchison J. Hepatitis C therapy in treatment-naive patients. Am J Med. 1999;107(6B):56S-61.
23. Reau N, et al. Evaluation of early null response to pegylated interferon and ribavirin as a predictor of therapeutic nonresponse in patients undergoing treatment for chronic hepatitis C. Am J Gastroenterol. 2011;106(3): 452-8.
24. Holmes JA, Desmond PV, Thompson AJ. Redefining baseline demographics: the role of genetic testing in hepatitis C virus infection. Clin Liver Dis. 2011;15(3):497-513.
25. Vachon ML, Dieterich DT. The HIV/HCV-co infected patient and new treatment options. Clin Liver Dis. 2011;15(3):585-96.
26. Ilyas JA, Vierling JM. An overview of emerging therapies for the treatment of chronic hepatitis C. Clin Liver Dis. 2011;15(3):515-36.
27. Mangia A, 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):2609-17.
28. von Wagner M, 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):522-7.
29. Parham P. The Immune System. 2 ed 2005: Garland Science Publishing.
30. Aghemo A, Colombo M. Peginterferon Alfa-2B versus peginterferon Alfa-: with ribavirin for the treatment of chronic hepatitis C: the pursuit of an ideal. Gastroenterology. 2010;138(1):386-9; discussion 389-90.
31. PEGASYS (peginterferon alfa-2a) Package Insert, H.-L.R. Inc., Editor: Nutley, NJ 07110.
32. PEG-Intron (peginterferon alfa-2b) Package Insert., a.s.o.M.C. Schering Corporation, INC., Editor: Whitehouse Station, NJ 08889, USA.
33. Crotty S, Cameron C, Andino R. Ribavirin's antiviral mechanism of action: lethal mutagenesis? J Mol Med (Berl). 2002;80(2):86-95.
34. Ribavirin Package Insert, I. Sandoz, Editor: Princeton, NJ 08540, USA.
35. Lee G, et al. Novel inhibitors of hepatitis C virus RNA-dependent RNA polymerases. J Mol Biol. 2006;357(4):1051-7.
36. Biswal BK, et al. Non-nucleoside inhibitors binding to hepatitis C virus NS5B polymerase reveal a novel mechanism of inhibition. J Mol Biol. 2006;361(1):33-45.
37. INCIVEK (telaprevir) Package Insert, V.P. Incorporated, Editor: Cambridge, MA 02139.
38. VICTRELIS (boceprevir) Package Insert, a.s.o.M.C. Schering Corporation, INC., Editor: Whitehouse Station, NJ 08889, USA.
39. Foster GR, et al. Telaprevir alone or with peginterferon and ribavirin reduces HCV RNA in patients with chronic genotype 2 but not genotype 3 infections. Gastroenterology. 2011;141(3):881-9 e1.
40. Kwo PY, et al. Efficacy of boceprevir, an NS3 protease inhibitor, in combination with peginterferon alfa-2b and ribavirin in treatment-naive patientswith genotype 1 hepatitis C infection (SPRINT-1): an open-label, randomised, multicentre phase 2 trial. Lancet. 2010;376(9742):705-16
41. Poordad F, et al. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med. 2011;364(13):1195-206.
42. Bacon BR, et al. Boceprevir for previously treated chronic HCV genotype 1 infection. N Engl J Med. 2011;364(13):1207-17.
43. Reesink HW, 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(4):997-1002.
44. McHutchison JG, et al. Telaprevir with peginterferon and ribavirin for chronic HCV genotype 1 infection. N Engl J Med. 2009;360(18):1827-38.
45. Liapakis A, Jacobson I. Telaprevir user's guide. Clin Liver Dis. 2011; 15(3):555-71.
46. McHutchison JG, et al. Telaprevir for previously treated chronic HCV infection. N Engl J Med. 2010;362(14):1292-303.
47. Jacobson IM, et al. Telaprevir for previously untreated chronic hepatitis Cvirus infection. N Engl J Med. 2011;364(25):2405-16.
48. Sherman KE, et al. Response-guided telaprevir combination treatment for hepatitis C virus infection. N Engl J Med. 2011;365(11):1014-24.
49. Foster GR, et al. Subanalyses of the telaprevir lead-in arm in the REALIZE Study: response at week 4 is not a substitute for prior null response categorization. J Hepatology. 2011;54(S1):S3.
50. Zeuzem S, et al. Telaprevir for retreatment of HCV infection. N Engl J Med. 2011;364(25):2417-8.
51. Noureddin M, Ghany MG. Pharmacokinetics and pharmacodynamics of peginterferon and ribavirin: implications for clinical efficacy in the treatment of chronic hepatitis C. Gastroenterol Clin North Am. 2010;39(3): 649-58.
52. Reau N, et al. Early predictors of anemia in patients with hepatitis C genotype 1 treated with peginterferon alfa-2a (40KD) plus ribavirin. Am J Gastroenterol. 2008;103(8):1981-8.
53. Del Rio RA, Post AB, Singer ME. Cost-effectiveness of hematologic growth factors for anemia occurring during hepatitis C combination therapy. Hepatology. 2006;44(6):1598-606.
54. Kelleher TB, Afdhal NH. Peginterferon and ribavirin for the treatment of chronic hepatitis C virus infection: Management of side effects. 2010. [cited November 15, 2011].
55. Jacobson IM, Brown RS, Frielich B. Weight-based Ribavirin dosing increases sustained virological response in patients with chronic hepatitis C: final results of the WIN-R study, a US community based trial. Hepatology. 2005;42(S1):749A.
56. Roomer R, et al. Thrombocytopenia and the risk of bleeding during treatment with peginterferon alfa and ribavirin for chronic hepatitis C. J Hepatol. 2010;53(3):455-9.
57. Afdhal N, et al. Final Results of ENABLE 1, a Phase 3, Multicenter Study of Eltrombopag as an Adjunct for Antiviral Treatment of Hepatitis C Virus-Related Chronic Liver Disease Associated With Thrombocytopenia. Hepatology. 2011;54(S1).
58. Dan AA, et al. Depression, anemia and health-related quality of life in chronic hepatitis C. J Hepatol. 2006;44(3):491-8.
59. Raison CL, et al. Paroxetine for prevention of depressive symptoms induced by interferon-alpha and ribavirin for hepatitis C. Aliment Pharmacol Ther. 2007;25(10):1163-74.
60. Kraus MR, et al. Therapy of interferon-induced depression in chronic hepatitis C with citalopram: a randomised, double-blind, placebo-controlled study. Gut. 2008;57(4):531-6.
61. Marcellin P, et al. Adherence to treatment and quality of life during hepatitis C therapy: a prospective, real-life, observational study. Liver Int. 2011;31(4):516-24.
62. Tine F. Patient's preferences for health scenarios associated with hepatitis C and its treatment. Patient Prefer Adherence. 2009;3:363-70.
63. Fraenkel L, et al. Patients' preferences for treatment of hepatitis C. Med Decis Making. 2010;30(1):45-57.
64. Schackman BR, et al. Quality-of-life tradeoffs for hepatitis C treatment: do patients and providers agree? Med Decis Making. 2008;28(2):233-42.
65. Witkos M, et al. Predictors of antiviral therapy in a post-transfusion cohort of hepatitis C patients. Can J Gastroenterol. 2006;20(2):107-11.
66. Alam I, et al. Enhanced adherence to HCV therapy with higher dose ribavirin formulation: final analyses from the ADHERE registry. Aliment Pharmacol Ther. 2010;32(4):535-42.
67. McHutchison JG, et al. Adherence to combination therapy enhances sustained response in genotype-1-infected patients with chronic hepatitis C. Gastroenterology. 2002;123(4):1061-9.
68. Lo Re V. 3rd, et al. Adherence to hepatitis C virus therapy and early virologic outcomes. Clin Infect Dis. 2009;48(2):186-93.
69. Brett Hauber A, et al. Patient preferences and assessment of likely adherence to hepatitis C virus treatment. J Viral Hepat. 2011;18(9):619-27.
70. Raptopoulou M, et al. The effect of adherence to therapy on sustained response in daily or three times a week interferon alpha-2b plus ribavirin treatment of naive and nonresponder chronic hepatitis C patients. J Viral Hepat. 2005;12(1):91-5.
71. Treadwell JR, Kearney D, Davila M. Health profile preferences of hepatitis C patients. Dig Dis Sci. 2000;45(2):345-50.
72. Ghany MG, et al. An update on treatment of genotype 1 chronic hepatitis C virus infection: 2011 practice guideline by the American Association for the Study of Liver Diseases. Hepatology. 2011;54(4):1433-44.
73. Pol S, et al. Once daily NS5A Inhibitor (BMS-790052) plus peginterferona2a and ribavirin produces high rates of extended rapid virologic response in treatment naive HCV genotype 1 subjects: phase 2a trial. Hepatology. 2010;52(S1):S462.
74. Ciesek S, von Hahn T, Manns MP. Second-wave protease inhibitors: choosing an heir. Clin Liver Dis. 2011;15(3):597-609.
75. Membreno FE, Lawitz EJ. The HCV NS5B nucleoside and non-nucleoside inhibitors. Clin Liver Dis. 2011;15(3):611-26.
76. Shi ST, et al. Preclinical characterization of PF-00868554, a potent nonnucleoside inhibitor of the hepatitis C virus RNA-dependent RNA polymerase. Antimicrob Agents Chemother. 2009;53(6):2544-52.
77. Ahn J, Flamm SL. Hepatitis C therapy: other players in the game. Clin Liver Dis. 2011;15(3):641-56.
78. Flisiak R, et al. The cyclophilin inhibitor Debio 025 combined with PEG IFNalpha2a significantly reduces viral load in treatment-naive hepatitis C patients. Hepatology. 2009;49(5):1460-8.
79. Gane EJ, et al. Oral combination therapy with a nucleoside polymerase inhibitor (RG7128) and danoprevir for chronic hepatitis C genotype 1 infection (INFORM-1): a randomised, double-blind, placebo-controlled, doseescalation trial. Lancet. 2010;376(9751):1467-75.
80. A study on the combination of RO5024048 and ritonavir-boosted danoprevir with and without Copegus (Ribavirin) in interferon-naïve patients with chronic hepatitis C genotype 1 (INFORM-SVR). http://clinicaltrials.gov/ct2/show/NCT01278134 2011. [cited November 29, 2011].
81. Zeuzem S, et al. The protease inhibitor GS-9256 and non-nucleoside polymerase inhibitor tegobuvir alone, with RBV or peginterferon plus RBV in hepatitis C. Hepatology. 2011.
82. Zeuzem S, et al, Efficacy of the Protease Inhibitor BI 201335, Polymerase Inhibitor BI 207127, and Ribavirin in Patients With Chronic HCV Infection. Gastroenterology. 2011;141(6):2047-55.
83. Gane EJ, et al. Once daily PSI-7977 plus RBV: Pegylated Interferon is not required for Complete Rapid Viral response in Treatment-Naïve Patients with HCV GT2 or GT3. Hepatology. 2011;54(S1):377A.
84. Lawitz E, et al. Once daily dual-nucleotide combination of PSI-938 and PSI-7977 provides 94% HCV RNA,LOD at day 14: First purine/pyrimidine clinical combination data (the NUCLEAR study). J Hepatol. 2011;54:S543.