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Treatment regimens for chronic hepatitis C virus genotype 1 infection in adults

Authors
Sanjiv Chopra, MD, MACP
Andrew J Muir, MD, MHS
Section Editor
Adrian M Di Bisceglie, MD
Deputy Editor
Allyson Bloom, MD

INTRODUCTION

Hepatitis C virus (HCV) can cause both acute and chronic hepatitis. The acute process is self-limited, rarely causes hepatic failure, and usually leads to chronic infection. Chronic HCV infection often follows a progressive course over many years and can ultimately result in cirrhosis, hepatocellular carcinoma, and the need for liver transplantation. (See "Clinical manifestations and natural history of chronic hepatitis C virus infection".)

The goal of treatment is to eradicate HCV RNA, which is predicted by the achievement of a sustained virologic response (SVR), defined by the absence of HCV RNA by polymerase chain reaction 12 weeks after stopping treatment. An SVR is associated with a 99 percent chance of being HCV RNA negative during long-term follow-up and can therefore be considered cure of the HCV infection [1]. Achievement of an SVR has also been associated with improved clinical outcomes. (See "Overview of the management of chronic hepatitis C virus infection", section on 'Goals of therapy'.)

This topic will review the antiviral treatment of patients with chronic genotype 1 HCV infection. General management of chronic HCV infection, evaluation and selection of patients for antiviral treatment, antiviral treatment of patients with other genotypes, and the treatment of acute HCV infection are discussed elsewhere:

(See "Overview of the management of chronic hepatitis C virus infection".)

(See "Patient evaluation and selection for antiviral therapy for chronic hepatitis C virus infection".)

                                   

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Literature review current through: Jul 2017. | This topic last updated: Jun 07, 2017.
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References
Top
  1. Swain MG, Lai MY, Shiffman ML, et al. A sustained virologic response is durable in patients with chronic hepatitis C treated with peginterferon alfa-2a and ribavirin. Gastroenterology 2010; 139:1593.
  2. Recommendations for Testing, Managing, and Treating Hepatitis C. Joint panel from the American Association of the Study of Liver Diseases and the Infectious Diseases Society of America. http://www.hcvguidelines.org/ (Accessed on August 01, 2016).
  3. European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu. EASL Recommendations on Treatment of Hepatitis C 2016. J Hepatol 2017; 66:153.
  4. Miller MH, Agarwal K, Austin A, et al. Review article: 2014 UK consensus guidelines - hepatitis C management and direct-acting anti-viral therapy. Aliment Pharmacol Ther 2014; 39:1363.
  5. World Health Organization. Guidelines for the screening, care, adn treatment of persons with hepatitis C infection. April 2014. http://apps.who.int/iris/bitstream/10665/111747/1/9789241548755_eng.pdf?ua=1 (Accessed on April 14, 2014).
  6. Lawitz E, Poordad FF, Pang PS, et al. Sofosbuvir and ledipasvir fixed-dose combination with and without ribavirin in treatment-naive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR): an open-label, randomised, phase 2 trial. Lancet 2014; 383:515.
  7. Gane EJ, Stedman CA, Hyland RH, et al. Efficacy of nucleotide polymerase inhibitor sofosbuvir plus the NS5A inhibitor ledipasvir or the NS5B non-nucleoside inhibitor GS-9669 against HCV genotype 1 infection. Gastroenterology 2014; 146:736.
  8. Afdhal N, Zeuzem S, Kwo P, et al. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med 2014; 370:1889.
  9. Feld JJ, Jacobson IM, Hézode C, et al. Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection. N Engl J Med 2015; 373:2599.
  10. Everson GT, Towner WJ, Davis MN, et al. Sofosbuvir With Velpatasvir in Treatment-Naive Noncirrhotic Patients With Genotype 1 to 6 Hepatitis C Virus Infection: A Randomized Trial. Ann Intern Med 2015; 163:818.
  11. Pianko S, Flamm SL, Shiffman ML, et al. Sofosbuvir Plus Velpatasvir Combination Therapy for Treatment-Experienced Patients With Genotype 1 or 3 Hepatitis C Virus Infection: A Randomized Trial. Ann Intern Med 2015; 163:809.
  12. Zeuzem S, Ghalib R, Reddy KR, et al. Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial. Ann Intern Med 2015; 163:1.
  13. Jacobsen I, Lawitz E, and Kwo P. An integrated analysis of 402 compensated cirrhotic patients with HCV genotype (gt) 1, 4, or 6 infection treated with elbasvir/grazoprevir. Presented at the American Association for the Study of Liver Diseases Liver Meeting, San Francisco CA, November 13-17, 2015.
  14. Thompson A, Zeuzem S, Rockstroh J, Kwo P, et al. The combination of elbasvir and grazoprevir ± RBV is highly effective for the treatment of GT1a-infected patients. Presented at the American Association for the Study of Liver Diseases Liver Meeting, San Francisco CA, November 13-17, 2015.
  15. Feld JJ, Kowdley KV, Coakley E, et al. Treatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. N Engl J Med 2014; 370:1594.
  16. Poordad F, Hezode C, Trinh R, et al. ABT-450/r-ombitasvir and dasabuvir with ribavirin for hepatitis C with cirrhosis. N Engl J Med 2014; 370:1973.
  17. Ferenci P, Bernstein D, Lalezari J, et al. ABT-450/r-ombitasvir and dasabuvir with or without ribavirin for HCV. N Engl J Med 2014; 370:1983.
  18. Lawitz E, Sulkowski MS, Ghalib R, et al. Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naive patients: the COSMOS randomised study. Lancet 2014; 384:1756.
  19. Pearlman BL, Ehleben C, Perrys M. The combination of simeprevir and sofosbuvir is more effective than that of peginterferon, ribavirin, and sofosbuvir for patients with hepatitis C-related Child's class A cirrhosis. Gastroenterology 2015; 148:762.
  20. Osinusi A, Meissner EG, Lee YJ, et al. Sofosbuvir and ribavirin for hepatitis C genotype 1 in patients with unfavorable treatment characteristics: a randomized clinical trial. JAMA 2013; 310:804.
  21. Sulkowski M, Rodriguez-Torres M, Lalezari J, et al. All-oral therapy with sofosbuvir plus ribavirin for the treatment of HCV genotype 1, 2, and 3 infection in patients co-infected with HIV (PHOTON-1). Presented at the 64th annual meeting of the American Association for the Study of Liver Diseases, Washington, DC, November 1-5, 2013. Abstract #212.
  22. Afdhal N, Reddy KR, Nelson DR, et al. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med 2014; 370:1483.
  23. Bourlière M, Bronowicki JP, de Ledinghen V, et al. Ledipasvir-sofosbuvir with or without ribavirin to treat patients with HCV genotype 1 infection and cirrhosis non-responsive to previous protease-inhibitor therapy: a randomised, double-blind, phase 2 trial (SIRIUS). Lancet Infect Dis 2015; 15:397.
  24. Bourliere M, Sulkowski M, Omata M, et al. An integrated safety and efficacy analysis of >500 patients with compensated cirrhosis treated with ledipasvir/sofosbuvir with or without ribavirin. Presented at the American Association for the Study of Liver Diseases Liver Meeting, Boston MA, November 7-11, 2014. Abstract #82.
  25. Zeuzem S, Mizokami M, Pianko S et al. Prevalence of pre-treatment NS5A resistance associated variants in genotype 1 patients across different regions using deep sequencing and effect on treatment outcome with LDV/SOF, Presented at the 66th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD). San Francisco, CA, November 13-17, 2015.
  26. Lawitz E, Gane E, Pearlman B, et al. Efficacy and safety of 12 weeks versus 18 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin for hepatitis C virus genotype 1 infection in previously untreated patients with cirrhosis and patients with previous null response with or without cirrhosis (C-WORTHY): a randomised, open-label phase 2 trial. Lancet 2015; 385:1075.
  27. Zeuzem S, Jacobson IM, Baykal T, et al. Retreatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. N Engl J Med 2014; 370:1604.
  28. Andreone P, Colombo MG, Enejosa JV, et al. ABT-450, ritonavir, ombitasvir, and dasabuvir achieves 97% and 100% sustained virologic response with or without ribavirin in treatment-experienced patients with HCV genotype 1b infection. Gastroenterology 2014; 147:359.
  29. Reddy KR, Bourlière M, Sulkowski M, et al. Ledipasvir and sofosbuvir in patients with genotype 1 hepatitis C virus infection and compensated cirrhosis: An integrated safety and efficacy analysis. Hepatology 2015; 62:79.
  30. Buti M, Gordon SC, Zuckerman E, et al. Grazoprevir, Elbasvir, and Ribavirin for Chronic Hepatitis C Virus Genotype 1 Infection After Failure of Pegylated Interferon and Ribavirin With an Earlier-Generation Protease Inhibitor: Final 24-Week Results From C-SALVAGE. Clin Infect Dis 2016; 62:32.
  31. Zepatier (elbasvir and grazoprevir). US FDA approved product information; Whitehouse Station, NJ: Merck and Co, Inc; January 2016.
  32. Bourlière M, Gordon SC, Flamm SL, et al. Sofosbuvir, Velpatasvir, and Voxilaprevir for Previously Treated HCV Infection. N Engl J Med 2017; 376:2134.
  33. Osinusi A, Kohli A, Marti MM, et al. Re-treatment of chronic hepatitis C virus genotype 1 infection after relapse: an open-label pilot study. Ann Intern Med 2014; 161:634.
  34. Wyles D, Pockros P, Morelli G, et al. Ledipasvir-sofosbuvir plus ribavirin for patients with genotype 1 hepatitis C virus previously treated in clinical trials of sofosbuvir regimens. Hepatology 2015; 61:1793.
  35. Poordad F, Felizarta F, Asatryan A, et al. Glecaprevir and pibrentasvir for 12 weeks for hepatitis C virus genotype 1 infection and prior direct-acting antiviral treatment. Hepatology 2017; 66:389.
  36. Lawitz E, Poordad F, Wells J, et al. Sofosbuvir-velpatasvir-voxilaprevir with or without ribavirin in direct-acting antiviral-experienced patients with genotype 1 hepatitis C virus. Hepatology 2017; 65:1803.
  37. Gane EJ, Shiffman ML, Etzkorn K, et al. Sofosbuvir-velpatasvir with ribavirin for 24 weeks in HCV patients previously treated with a direct-acting antiviral regimen. Hepatology 2017.
  38. Cooper C, Naggie S, Saag M, et al. Successful Re-treatment of Hepatitis C Virus in Patients Coinfected With HIV Who Relapsed After 12 Weeks of Ledipasvir/Sofosbuvir. Clin Infect Dis 2016; 63:528.
  39. FDA Drug Safety Communication: FDA warns of serious liver injury risk with hepatitis C treatments Viekira Pak and Technivie. October 22, 2015. http://www.fda.gov/Drugs/DrugSafety/ucm468634.htm (Accessed on October 22, 2015).
  40. Hézode C, Fontaine H, Dorival C, et al. Triple therapy in treatment-experienced patients with HCV-cirrhosis in a multicentre cohort of the French Early Access Programme (ANRS CO20-CUPIC) - NCT01514890. J Hepatol 2013; 59:434.
  41. Afdhal NH, Reau N, Everson GT, et al. Safety and efficacy of telaprevir (TVR) or boceprevir (BOC) in patientns with cirrhosis: Interim results of a longitudinal, observational study. Presented at the 64th annual meeting of the American Association for the Study of Liver Diseases, Washington, DC, November 1-5, 2013.
  42. Charlton M, Everson GT, Flamm SL, et al. Ledipasvir and Sofosbuvir Plus Ribavirin for Treatment of HCV Infection in Patients With Advanced Liver Disease. Gastroenterology 2015; 149:649.
  43. Manns M, Samuel D, Gane EJ, et al. Ledipasvir and sofosbuvir plus ribavirin in patients with genotype 1 or 4 hepatitis C virus infection and advanced liver disease: a multicentre, open-label, randomised, phase 2 trial. Lancet Infect Dis 2016; 16:685.
  44. Curry MP, O'Leary JG, Bzowej N, et al. Sofosbuvir and Velpatasvir for HCV in Patients with Decompensated Cirrhosis. N Engl J Med 2015; 373:2618.
  45. Poordad F, Schiff ER, Vierling JM, et al. Daclatasvir with sofosbuvir and ribavirin for hepatitis C virus infection with advanced cirrhosis or post-liver transplantation recurrence. Hepatology 2016; 63:1493.
  46. Poordad F, McCone J Jr, Bacon BR, et al. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med 2011; 364:1195.
  47. Jacobson IM, McHutchison JG, Dusheiko G, et al. Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med 2011; 364:2405.
  48. Kowdley KV, Gordon SC, Reddy KR, et al. Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. N Engl J Med 2014; 370:1879.
  49. Mizokami M, Yokosuka O, Takehara T, et al. Ledipasvir and sofosbuvir fixed-dose combination with and without ribavirin for 12 weeks in treatment-naive and previously treated Japanese patients with genotype 1 hepatitis C: an open-label, randomised, phase 3 trial. Lancet Infect Dis 2015; 15:645.
  50. Terrault NA, Zeuzem S, Di Bisceglie AM, et al. Effectiveness of Ledipasvir-Sofosbuvir Combination in Patients With Hepatitis C Virus Infection and Factors Associated With Sustained Virologic Response. Gastroenterology 2016; 151:1131.
  51. Wyles DL, Pockros PJ, Yang JC, et al. Retreatment of patients who failed prior sofosbuvir-based regimens with all oral fixed-dose combination ledipasvir-sofosbuvir plus ribavirin for 12 weeks. Presented at the American Association for the Study of Liver Diseases Liver Meeting, Boston MA, November 7-11, 2014. Abstract #235
  52. Alqahtani SA, Afdhal N, Zeuzem S, et al. Safety and tolerability of ledipasvir/sofosbuvir with and without ribavirin in patients with chronic hepatitis C virus genotype 1 infection: Analysis of phase III ION trials. Hepatology 2015; 62:25.
  53. Foster GR, Afdhal N, Roberts SK, et al. Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection. N Engl J Med 2015; 373:2608.
  54. Sulkowski M, Hezode C, Gerstoft J, et al. Efficacy and safety of 8 weeks versus 12 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin in patients with hepatitis C virus genotype 1 mono-infection and HIV/hepatitis C virus co-infection (C-WORTHY): a randomised, open-label phase 2 trial. Lancet 2015; 385:1087.
  55. Jacobson, F Poordad, R Firpi-Morell, et al. Efficacy and safety af grazoprevir and elbasvir in hepatitis C genotype 1-infected patients with Child-Pugh class B cirrhosis (C-SALT Part A). Presented at the 2015 International Liver Congress: 50th Annual Meeting of the European Association for the Study of the Liver (EASL). Vienna, April 22-26, 2015. Abstract O008.
  56. Dore G, Altice F, Litwin AH, et al. C-EDGE CO-STAR: Efficacy of grazoprevir and elbasvir in persons who inject drugs (PWID) receiving opioid agonist therapy. Presented at the American Association for the Study of Liver Diseases Liver Meeting, San Francisco CA, November 13-17, 2015. Abstract #40.
  57. D Roth, D Nelson, A Bruchfeld, et al. C-SURFER: grazoprevir plus elbasvir in treatment-naive and treatment-experienced patients with hepatitis C virus genotype 1 infection and chronic kidney disease. Presented at the 2015 International Liver Congress: 50th Annual Meeting of the European Association for the Study of the Liver (EASL). Vienna, April 22-26, 2015. Abstract LP02.
  58. JK Rockstroh, M Nelson, C Katlama, et al. C-EDGE co-infected: phase 3 study of grazoprevir/elbasvir in patients with HCV/HIV. Presented at the 2015 International Liver Congress: 50th Annual Meeting of the European Association for the Study of the Liver (EASL). Vienna, April 22-26, 2015. Abstract P0887.
  59. Kowdley KV, Lawitz E, Poordad F, et al. Phase 2b trial of interferon-free therapy for hepatitis C virus genotype 1. N Engl J Med 2014; 370:222.
  60. Dore GJ, Conway B, Luo Y, et al. Efficacy and safety of ombitasvir/paritaprevir/r and dasabuvir compared to IFN-containing regimens in genotype 1 HCV patients: The MALACHITE-I/II trials. J Hepatol 2016; 64:19.
  61. Lawitz E, Makara M, Akarca US, et al. Efficacy and Safety of Ombitasvir, Paritaprevir, and Ritonavir in an Open-Label Study of Patients With Genotype 1b Chronic Hepatitis C Virus Infection With and Without Cirrhosis. Gastroenterology 2015; 149:971.
  62. Feld JJ, Moreno C, Trinh R, et al. Sustained virologic response of 100% in HCV genotype 1b patients with cirrhosis receiving ombitasvir/paritaprevir/r and dasabuvir for 12weeks. J Hepatol 2016; 64:301.
  63. Poordad F, Lawitz E, Kowdley KV, et al. Exploratory study of oral combination antiviral therapy for hepatitis C. N Engl J Med 2013; 368:45.
  64. Lawitz E, Hezode C, Varunok P, et al. Interferon- and ribavirin-free regimen of ABT-450/r + ABT-267 in HCV genotype 1b infected treatment naive patients and prior null responders. Presented at the 64th annual meeting of the American Association for the Study of Liver Diseases, Washington, DC, November 1-5, 2013.
  65. VIEKIRA PAK (ombitasvir, paritaprevir, and ritonavir tablets; dasabuvir tablets). US FDA approved product information. National Library of Medicine. www.dailymed.nlm.nih.gov (Accessed on January 01, 2015).
  66. Kwo P, Gitlin N, Nahass R, et al. A phase 3, randomised, open-label study to evaluate the efficacy and safety of 8 and 12 weeks of simeprevir (SMV) plus sofosbuvir (SOF) in treatment-naive and -experienced patients with chronic HCV genotype 1 infection without cirrhosis: OPTIMIST-1. Presented at the 50th Annual Meeting of the European Association for the Study of the Liver (EASL), Vienna Austria, April 22-26, 2015.
  67. Lawitz E, Matusow G, DeJesus E, et al. A phase 3, open-label, single-arm study to evaluate the efficacy and safety of 12 weeks of simeprevir (SMV) plus sofosbuvir (SOF) in treatment-naive or -experienced patients with chronic HCV genotype 1 infection and cirrhosis: OPTIMIST-2. Presented at the 50th Annual Meeting of the European Association for the Study of the Liver (EASL), Vienna Austria, April 22-26, 2015.
  68. Olysio (simeprevir). US FDA approved product information. National Library of Medicine. Available online at http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=1816fd68-0ed7-4a37-84bb-e298c5ab6e28 (Accessed on November 17, 2014).
  69. Sulkowski MS, Vargas HE, Di Bisceglie AM, et al. Effectiveness of Simeprevir Plus Sofosbuvir, With or Without Ribavirin, in Real-World Patients With HCV Genotype 1 Infection. Gastroenterology 2016; 150:419.
  70. Jesnsen DM, O'Leary J, Pockros, P, et al. Safety and efficacy of sofosbuvir-containing regimens for hepatitis C: Real world experience in a diverse, longitudinal observational cohort. Presented at the American Association for the Study of Liver Diseases Liver Meeting, Boston MA, November 7-11, 2014.
  71. Dieterich D, Bacon B, FlammS, et al. Evaluation of sofosbuvir and simeprevir-based regimens in the TRIO network: Academic and community treatment of a real-world, heterogenous population. Presented at the American Association for the Study of Liver Diseases Liver Meeting, Boston MA, November 7-11, 2014.
  72. Aqel BA, Pungpapong S, Leise M, et al. Multicenter experience using simeprevir and sofosbuvir with or without ribavirin to treat hepatitis C genotype 1 in patients with cirrhosis. Hepatology 2015; 62:1004.
  73. Williams JA, Ring BJ, Cantrell VE, et al. Comparative metabolic capabilities of CYP3A4, CYP3A5, and CYP3A7. Drug Metab Dispos 2002; 30:883.
  74. Sulkowski MS, Gardiner DF, Rodriguez-Torres M, et al. Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection. N Engl J Med 2014; 370:211.
  75. Wyles DL, Ruane PJ, Sulkowski MS, et al. Daclatasvir plus Sofosbuvir for HCV in Patients Coinfected with HIV-1. N Engl J Med 2015; 373:714.
  76. Poordad F, Schiff ER, Vierling JM, et al. Daclatasvir, sofosbuvir, and ribavirin combination for HCV patients with advanced cirrhosis or post-transplant recurrence: ALLY-1 phase 3 study. Presented at the 50th Annual Meeting of the European Association for the Study of the Liver (EASL), Vienna Austria, April 22-26, 2015.
  77. Hezode C, De Ledinghen V, Fonatine H, et al. Daclatasvir plus sofosbuvir with or without ribavirin in patients with HCV genotype 3 infection: Interim analysis of a French multicenter compassionate use program. Presented at the 50th Annual Meeting of the European Association for the Study of the Liver (EASL), Vienna Austria, April 22-26, 2015. Vienna, Austria. Abstract LP05
  78. Foster GR, McLaughlan J, Irving W, et al.Treatment of decompensated HCV cirrhosis in patients with diverse genotypes: 12 weeks of sofosbuvir and NS5A inhibitors with/without ribavirin is effective in HCV genotypes 1 and 3.Presented at the 50th Annual Meeting of the European Association for the Study of the Liver (EASL), Vienna Austria, April 22-26, 2015. Abstract O002
  79. Lawitz E, Mangia A, Wyles D, et al. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med 2013; 368:1878.
  80. Lawitz E, Lalezari JP, Hassanein T, et al. Sofosbuvir in combination with peginterferon alfa-2a and ribavirin for non-cirrhotic, treatment-naive patients with genotypes 1, 2, and 3 hepatitis C infection: a randomised, double-blind, phase 2 trial. Lancet Infect Dis 2013; 13:401.
  81. Kowdley KV, Lawitz E, Crespo I, et al. Sofosbuvir with pegylated interferon alfa-2a and ribavirin for treatment-naive patients with hepatitis C genotype-1 infection (ATOMIC): an open-label, randomised, multicentre phase 2 trial. Lancet 2013; 381:2100.
  82. Sovaldi (sofosbuvir). US FDA approved product information; Foster City, CA: Gilead Sciences; December 2013.
  83. Pol S, Sulkowski M, Hassanein T, et al. Successful retreatment of HCV genotype-1 infected patients who failed prior therapy with peginterferon plus ribavirin plus 1 or 2 other direct-acting antiviral agents with sofosbuvir. Presented at the 49th Annual Meeting of the European Association for the Study of the Liver (EASL), London UK, April 9-13, 2014.
  84. FDA. Olysio U.S. prescribing information http://www.accessdata.fda.gov/drugsatfda (Accessed on October 15, 2014).
  85. Jacobson IM, Dore GJ, Foster GR, et al. Simeprevir with pegylated interferon alfa 2a plus ribavirin in treatment-naive patients with chronic hepatitis C virus genotype 1 infection (QUEST-1): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet 2014; 384:403.
  86. Manns M, Marcellin P, Poordad F, et al. Simeprevir with pegylated interferon alfa 2a or 2b plus ribavirin in treatment-naive patients with chronic hepatitis C virus genotype 1 infection (QUEST-2): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 2014; 384:414.
  87. Hayashi N, Izumi N, Kumada H, et al. Simeprevir with peginterferon/ribavirin for treatment-naïve hepatitis C genotype 1 patients in Japan: CONCERTO-1, a phase III trial. J Hepatol 2014; 61:219.
  88. Forns X, Lawitz E, Zeuzem S, et al. Simeprevir with peginterferon and ribavirin leads to high rates of SVR in patients with HCV genotype 1 who relapsed after previous therapy: a phase 3 trial. Gastroenterology 2014; 146:1669.
  89. Zeuzem S, Berg T, Gane E, et al. Simeprevir increases rate of sustained virologic response among treatment-experienced patients with HCV genotype-1 infection: a phase IIb trial. Gastroenterology 2014; 146:430.
  90. Marcellin P, Forns X, Goeser T, et al. Telaprevir is effective given every 8 or 12 hours with ribavirin and peginterferon alfa-2a or -2b to patients with chronic hepatitis C. Gastroenterology 2011; 140:459.
  91. Silva M, Poo J, Wagner F, et al. A randomised trial to compare the pharmacokinetic, pharmacodynamic, and antiviral effects of peginterferon alfa-2b and peginterferon alfa-2a in patients with chronic hepatitis C (COMPARE). J Hepatol 2006; 45:204.
  92. McHutchison JG, Lawitz EJ, Shiffman ML, et al. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med 2009; 361:580.
  93. Di Bisceglie AM, Ghalib RH, Hamzeh FM, Rustgi VK. Early virologic response after peginterferon alpha-2a plus ribavirin or peginterferon alpha-2b plus ribavirin treatment in patients with chronic hepatitis C. J Viral Hepat 2007; 14:721.
  94. Laguno M, Cifuentes C, Murillas J, et al. Randomized trial comparing pegylated interferon alpha-2b versus pegylated interferon alpha-2a, both plus ribavirin, to treat chronic hepatitis C in human immunodeficiency virus patients. Hepatology 2009; 49:22.
  95. Rumi MG, Aghemo A, Prati GM, et al. Randomized study of peginterferon-alpha2a plus ribavirin vs peginterferon-alpha2b plus ribavirin in chronic hepatitis C. Gastroenterology 2010; 138:108.
  96. Ascione A, De Luca M, Tartaglione MT, et al. Peginterferon alfa-2a plus ribavirin is more effective than peginterferon alfa-2b plus ribavirin for treating chronic hepatitis C virus infection. Gastroenterology 2010; 138:116.
  97. Awad T, Thorlund K, Hauser G, et al; Cochrane Hepato-Biliary Group. Peginterferon alpha-2a may achieve higher sustained virological response than peginteferon alpha-2b in chronic hepatitis C: a Cochrane systematic review of randomized clinical trials. Hepatology 2009; 50(Suppl):707A.
  98. Di Bisceglie AM, Shiffman ML, Everson GT, et al. Prolonged therapy of advanced chronic hepatitis C with low-dose peginterferon. N Engl J Med 2008; 359:2429.