Welcome to the CCO Site

Thank you for your interest in CCO content. As a guest, please complete the following information fields. These data help ensure our continued delivery of impactful education. 

Become a member (or login)? Member benefits include accreditation certificates, downloadable slides, and decision support tools.

Submit

Management of Hepatitis C Infection

Stefan Zeuzem, MD
Program Director
Jordan J. Feld, MD, MPH
Hemant Shah, MD, MScCH HPTE
Released: June 17, 2019
Back Next

References

  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;139:1593-1601.
  2. Yoshida EM, Sulkowski MS, Gane EJ, et al. Concordance of sustained virological response 4, 12, and 24 weeks post-treatment with sofosbuvir-containing regimens for hepatitis C virus. Hepatology. 2015;61:41-45.
  3. Backus LI, Boothroyd DB, Phillips BR, et al. A sustained virologic response reduces risk of all-cause mortality in patients with hepatitis C. Clin Gastroenterol Hepatol. 2011;9:509-516.
  4. Morgan TR, Ghany MG, Kim HY, et al. Outcome of sustained virological responders with histologically advanced chronic hepatitis C. Hepatology. 2010;52:833-844.
  5. Veldt BJ, Heathcote EJ, Wedemeyer H, et al. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Ann Intern Med. 2007;147:677-684.
  6. Shiffman ML, Morishima C, Dienstag JL, et al. Effect of HCV RNA suppression during peginterferon alfa-2a maintenance therapy on clinical outcomes in the HALT-C trial. Gastroenterology. 2009;137:1986-1994.
  7. van der Meer AJ, Veldt BJ, Feld JJ, et al. Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis. JAMA. 2012;308:2584-2593.
  8. Afdhal N, Everson G, Calleja JL, et al. Sofosbuvir and ribavirin for the treatment chronic HCV with cirrhosis and portal hypertension with and without decompensation: early virologic response and safety. Program and abstracts of the 49th Annual Meeting of the European Association for the Study of the Liver; April 9-13, 2014; London, England. Abstract O68.
  9. Martin NK, Hickman M, Hutchinson SJ, et al. Combination interventions to prevent HCV transmission among people who inject drugs: modeling the impact of antiviral treatment, needle and syringe programs, and opiate substitution therapy. Clin Infect Dis. 2013;57(suppl 2):S39-S45.
  10. Martin NK, Vickerman P, Grebely J, et al. Hepatitis C virus treatment for prevention among people who inject drugs: modeling treatment scale-up in the age of direct-acting antivirals. Hepatology. 2013;58:1598-1609.
  11. Scheel TK, Rice CM. Understanding the hepatitis C virus life cycle paves the way for highly effective therapies. Nat Med. 2013;19:837-849.
  12. Horner SM, Gale M. Regulation of hepatic innate immunity by hepatitis C virus. Nat Med. 2013;19:879-888.
  13. Burger D, Back D, Buggisch P, et al. Clinical management of drug-drug interactions in HCV therapy: challenges and solutions. J Hepatol. 2013;58:792-800.
  14. US Food and Drug Administration. Ombitasvir/paritaprevir/ritonavir and dasabuvir. Available at: http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=206619. Accessed May 15, 2019.
  15. European Medicines Agency. Ombitasvir/paritaprevir/ritonavir plus dasabuvir. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003839/WC500183997.pdf. Accessed May 15, 2019.
  16. US Food and Drug Administration. Ombitasvir; paritaprevir; ritonavir. Available at: http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=207931. Accessed May 15, 2019.
  17. US Food and Drug Administration. Elbasvir/grazoprevir. Available at: http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=208261. Accessed May 15, 2019.
  18. US Food and Drug Administration. Sofosbuvir/velpatasvir/voxilaprevir. Available at: http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=209195. Accessed May 15, 2019.
  19. European Medicines Agency. Sofosbuvir/velpatasvir/voxilaprevir. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/004350/WC500235373.pdf. Accessed May 15, 2019.
  20. Bourlière M, Gordon SC, Flamm SL, et al. Sofosbuvir, velpatasvir, and voxilaprevir for previously treated HCV infection. N Engl J Med. 2017;376:2134-2146.
  21. US Food and Drug Administration. Glecaprevir/pibrentasvir. Available at: http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=209394. Accessed May 15, 2019.
  22. European Medicines Agency. Glecaprevir/pibrentasvir. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/004430/WC500233677.pdf. Accessed May 15, 2019.
  23. US Food and Drug Administration. Sofosbuvir. Available at: http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=204671. Accessed May 15, 2019.
  24. Sovaldi summary of product characteristics. Available at: http://www.medicines.org.uk/emc/medicine/28539/SPC/Sovaldi+400+mg+film+coated+tablets/. Accessed May 15, 2019.
  25. US Food and Drug Administration. Ledipasvir/sofosbuvir. Available at: http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=205834. Accessed May 15, 2019.
  26. European Medicines Agency. Ledipasvir/sofosbuvir. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003850/WC500177995.pdf. Accessed May 15, 2019.
  27. US Food and Drug Administration. Sofosbuvir/velpatasvir. Available at: http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=208341. Accessed May 15, 2019.
  28. European Medicines Agency. Sofosbuvir/velpatasvir. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/004210/WC500211151.pdf. Accessed May 15, 2019.
  29. US Food and Drug Administration. Daclatasvir. Available at: http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=206843. Accessed May 15, 2019.
  30. Lam AM, Espiritu C, Bansal S, et al. Genotype and subtype profiling of PSI-7977 as a nucleotide inhibitor of hepatitis C virus. Antimicrob Agents Chemother. 2012;56:3359-3368.
  31. Lawitz E, Poordad F, Brainard DM, et al. Sofosbuvir with peginterferon-ribavirin for 12 weeks in previously treated patients with hepatitis C genotype 2 or 3 and cirrhosis. Hepatology. 2015;61:769-775.
  32. US Food and Drug Administration. Dasabuvir/ombitasvir/paritaprevir/ritonavir. Available at: http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=208624. Accessed May 15, 2019.
  33. Tellinghuisen TL, Foss KL, Treadaway JC, Rice CM. Identification of residues required for RNA replication in domains II and III of the hepatitis C virus NS5A protein. J Virol. 2008;82:1073-1083.
  34. Appel N, Zayas M, Miller S, et al. Essential role of domain III of nonstructural protein 5a for hepatitis C virus infectious particle assembly. PLoS Pathog. 2008;4:e1000035.
  35. Neddermann P, Quintavalle M, Di Pietro C, et al. Reduction of hepatitis C virus NS5A hyperphosphorylation by selective inhibition of cellular kinases activates viral RNA replication in cell culture. J Virol. 2004;78:13306-13314.
  36. Tapper EB, Bacon BR, Curry MP, et al. Real-world effectiveness for 12 weeks of ledipasvir-sofosbuvir for genotype 1 hepatitis C: the Trio Health study. J Viral Hepat. 2017;24:22-27.
  37. Backus LI, Belperio PS, Shahoumian TA, Loomis TP, Mole LA. Real-world effectiveness of ledipasvir/sofosbuvir in 4,365 treatment-naive, genotype 1 hepatitis C-infected patients. Hepatology. 2016;64:405-414.
  38. 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;151:1131-1140.
  39. Afdhal N, Zeuzem S, Kwo P, et al. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014;370:1889-1898.
  40. Afdhal N, Reddy KR, Nelson DR, et al. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med. 2014;370:1483-1493.
  41. 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;370:1879-1888.
  42. European Medicines Agency. Daclatasvir. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003768/WC500172848.pdf. Accessed May 15, 2019.
  43. Bifano M, Hwang C, Oosterhuis B, et al. Assessment of pharmacokinetic interactions of the HCV NS5A replication complex inhibitor daclatasvir with antiretroviral agents: ritonavir-boosted atazanavir, efavirenz and tenofovir. Antivir Ther. 2013;18:931-940.
  44. Feld JJ, Hoofnagle JH. Mechanism of action of interferon and ribavirin in treatment of hepatitis C. Nature. 2005;436:967-972.
  45. Hézode C, Forestier N, Dusheiko G, et al. Telaprevir and peginterferon with or without ribavirin for chronic HCV infection. N Engl J Med. 2009;360:1839-1850.
  46. Kwo PY, Lawitz EJ, McCone J, et al. Efficacy of boceprevir, an NS3 protease inhibitor, in combination with peginterferon alfa-2b and ribavirin in treatment-naive patients with genotype 1 hepatitis C infection (SPRINT-1): an open-label, randomised, multicentre phase 2 trial. Lancet. 2010;376:705-716.
  47. US Food and Drug Administration. Simeprevir. Available at: http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=205123. Accessed May 15, 2019.
  48. Olysio summary of product characteristics. Available at: http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002777/human_med_001766.jsp&mid=WC0b01ac058001d124. Accessed May 15, 2019.
  49. Kwo P, Gitlin N, Nahass R, et al. Simeprevir plus sofosbuvir (12 and 8 weeks) in hepatitis C virus genotype 1-infected patients without cirrhosis: OPTIMIST-1, a phase 3, randomized study. Hepatology. 2016;64:370-380.
  50. US Food and Drug Administration. Peginterferon alfa-2a. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=103964. Accessed May 15, 2019.
  51. US Food and Drug Administration. Peginterferon alfa-2b. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=103949. Accessed May 15, 2019.
  52. European Medicines Agency. Peginterferon alfa-2a. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000395/WC500039195.pdf. Accessed May 15, 2019.
  53. European Medicines Agency. Peginterferon alfa-2b. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000280/WC500039388.pdf. Accessed May 15, 2019.
  54. American Association for the Study of Liver Diseases and the Infectious Diseases Society of America. HCV guidance: recommendations for testing, managing, and treating hepatitis C. Updated May 24, 2018. Available at: https://www.hcvguidelines.org/sites/default/files/full-guidance-pdf/HCVGuidance_May_24_2018b.pdf. Accessed May 15, 2019.
  55. Sangiovanni A, Prati GM, Fasani P, et al. The natural history of compensated cirrhosis due to hepatitis C virus: a 17-year cohort study of 214 patients. Hepatology. 2006;43:1303-1310.
  56. Everson GT, Hoefs JC, Seeff LB, et al. Impact of disease severity on outcome of antiviral therapy for chronic hepatitis C: Lessons from the HALT-C trial. Hepatology. 2006;44:1675-1684.
  57. 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;359:2429-2441.
  58. Dienstag JL, Ghany MG, Morgan TR, et al. A prospective study of the rate of progression in compensated, histologically advanced chronic hepatitis C. Hepatology. 2011;54:396-405.
  59. Neumann UP, Berg T, Bahra M, et al. Fibrosis progression after liver transplantation in patients with recurrent hepatitis C. J Hepatol. 2004;41:830-836.
  60. Charlton M, Seaberg E, Wiesner R, et al. Predictors of patient and graft survival following liver transplantation for hepatitis C. Hepatology. 1998;28:823-830.
  61. Forman LM, Lewis JD, Berlin JA, Feldman HI, Lucey MR. The association between hepatitis C infection and survival after orthotopic liver transplantation. Gastroenterology. 2002;122:889-896.
  62. Everson GT. Treatment of patients with hepatitis C virus on the waiting list. Liver Transpl. 2003;9:S90-S94.
  63. Forns X, Navasa M, Rodes J. Treatment of HCV infection in patients with advanced cirrhosis. Hepatology. 2004;40:498.
  64. Everson GT, Trotter J, Forman L, et al. Treatment of advanced hepatitis C with a low accelerating dosage regimen of antiviral therapy. Hepatology. 2005;42:255-262.
  65. Curry MP, Forns X, Chung RT, et al. Sofosbuvir and ribavirin prevent recurrence of HCV infection after liver transplantation: an open-label study. Gastroenterology. 2015;148:100-107.e1.
  66. Charlton MR, Gane E, Manns M, et al. Sofosbuvir and ribavirin for the treatment of compensated recurrent hepatitis C virus infection after liver transplantation. Gastroenterology. 2015;148:108-117.
  67. Forns X, Charlton M, Denning J, et al. Sofosbuvir compassionate use program for patients with severe recurrent hepatitis C after liver transplantation. Hepatology. 2015;61:1485-1495.
  68. Benhamou Y, Bochet M, Di Martino V, et al. Liver fibrosis progression in human immunodeficiency virus and hepatitis C virus coinfected patients. The Multivirc Group. Hepatology. 1999;30:1054-1058.
  69. Macias J, Berenguer J, Japon MA, et al. Fast fibrosis progression between repeated liver biopsies in patients coinfected with human immunodeficiency virus/hepatitis C virus. Hepatology. 2009;50:1056-1063.
  70. Konerman MA, Mehta SH, Sutcliffe CG, et al. Fibrosis progression in human immunodeficiency virus/hepatitis C virus coinfected adults: prospective analysis of 435 liver biopsy pairs. Hepatology. 2014;59:767-775.
  71. Pineda JA, Romero-Gómez M, Díaz-García F, et al. HIV coinfection shortens the survival of patients with hepatitis C virus-related decompensated cirrhosis. Hepatology. 2005;41:779-789.
  72. Merchante N, Giron-Gonzalez JA, Gonzalez-Serrano M, et al. Survival and prognostic factors of HIV-infected patients with HCV-related end-stage liver disease. AIDS. 2006;20:49-57.
  73. Terrault NA, Roland ME, Schiano T, et al. Outcomes of liver transplant recipients with hepatitis C and human immunodeficiency virus coinfection. Liver Transpl. 2012;18:716-726.
  74. Johnson RJ, Gretch DR, Yamabe H, et al. Membranoproliferative glomerulonephritis associated with hepatitis C virus infection. N Engl J Med. 1993;328:465-470.
  75. Saadoun D, Resche Rignon M, Thibault V, et al. Peg-IFNα/ribavirin/protease inhibitor combination in hepatitis C virus associated mixed cryoglobulinemia vasculitis; results at week 24. Ann Rheum Dis. 2014;73:831-837.
  76. Johnson RJ, Gretch DR, Couser WG, et al. Hepatitis C virus-associated glomerulonephritis. Effect of alpha-interferon therapy. Kidney Int. 1994;46:1700-1704.
  77. Foster GR, Goldin RD, Thomas HC. Chronic hepatitis C virus infection causes a significant reduction in quality of life in the absence of cirrhosis. Hepatology. 1998;27:209-212.
  78. Bonkovsky HL, Snow KK, Malet PF, et al. Health-related quality of life in patients with chronic hepatitis C and advanced fibrosis. J Hepatol. 2007;46:420-431.
  79. Sarkar S, Jiang Z, Evon DM, Wahed AS, Hoofnagle JH. Fatigue before, during and after antiviral therapy of chronic hepatitis C: results from the Virahep-C study. J Hepatol. 2012;57:946-952.
  80. Younossi ZM, Stepanova M, Henry L. Effects of sofosbuvir-based treatment, with and without interferon, on outcome and productivity of patients with chronic hepatitis C. Clin Gastroenterol Hepatol. 2014;12:1349-1359.
  81. Gerber L, Estep M, Stepanova M, et al. Effects of viral eradication with ledipasvir and sofosbuvir, with or without ribavirin, on measures of fatigue in patients with chronic hepatitis C virus infection. Clin Gastroenterol Hepatol. 2016;14:156-164.
  82. Younossi ZM, Stepanova M, Afdhal N, et al. Improvement of health-related quality of life and work productivity in chronic hepatitis C patients with early and advanced fibrosis treated with ledipasvir and sofosbuvir. J Hepatol. 2014;63:337-345.
  83. Petta S, Cammà C, Di Marco V, et al. Insulin resistance and diabetes increase fibrosis in the liver of patients with genotype 1 HCV infection. Am J Gastroenterol. 2008;103:1136-1144.
  84. Hung CH, Wang JH, Hu TH, et al. Insulin resistance is associated with hepatocellular carcinoma in chronic hepatitis C infection. World J Gastroenterol. 2010;16:2265-2271.
  85. Arase Y, Suzuki F, Suzuki Y, et al. Sustained virological response reduces incidence of onset of type 2 diabetes in chronic hepatitis C. Hepatology. 2009;49:739-744.
  86. Hsu YC, Lin JT, Ho HJ, et al. Antiviral treatment for hepatitis C virus infection is associated with improved renal and cardiovascular outcomes in diabetic patients. Hepatology. 2014;59:1293-1302.
  87. Martin NK, Hickman M, Hutchinson SJ, Goldberg DJ, Vickerman P. Combination interventions to prevent HCV transmission among people who inject drugs: modeling the impact of antiviral treatment, needle and syringe programs, and opiate substitution therapy. Clin Infect Dis. 2013;57(suppl 2):S39-S45.
  88. European Association for the Study of the Liver. EASL recommendations on treatment of hepatitis C 2018. Available at: Accessed May 15, 2019.
  89. Schaefer M, Sarkar R, Knop V, et al. Escitalopram for the prevention of peginterferon-α2a-associated depression in hepatitis C virus-infected patients without previous psychiatric disease: a randomized trial. Ann Intern Med. 2012;157:94-103.
  90. Talwalkar JA, Kurtz DM, Schoenleber SJ, West CP, Montori VM. Ultrasound-based transient elastography for the detection of hepatic fibrosis: systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2007;5:1214-1220.
  91. Friedrich-Rust M, Ong MF, Martens S, et al. Performance of transient elastography for the staging of liver fibrosis: a meta-analysis. Gastroenterology. 2008;134:960-974.
  92. Ziol M, Handra-Luca A, Kettaneh A, et al. Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with chronic hepatitis C. Hepatology. 2005;41:48-54.
  93. Castéra L, Foucher J, Bernard PH, et al. Pitfalls of liver stiffness measurement: a 5-year prospective study of 13,369 examinations. Hepatology. 2010;51:828-835.
  94. Lebray P, Varnous S, Charlotte F, Varaut A, Poynard T, Ratziu V. Liver stiffness is an unreliable marker of liver fibrosis in patients with cardiac insufficiency. Hepatology. 2008;48:2089.
  95. Hirooka M, Koizumi Y, Hiasa Y, et al. Hepatic elasticity in patients with ascites: evaluation with real-time tissue elastography. AJR Am J Roentgenol. 2011;196:W766-W771.
  96. Myers RP, Pomier-Layrargues G, Kirsch R, et al. Feasibility and diagnostic performance of the FibroScan XL probe for liver stiffness measurement in overweight and obese patients. Hepatology. 2012;55:199-208.
  97. Castéra L, Le Bail B, Roudot-Thoraval F, et al. Early detection in routine clinical practice of cirrhosis and oesophageal varices in chronic hepatitis C: comparison of transient elastography (FibroScan) with standard laboratory tests and non-invasive scores. J Hepatol. 2009;50:59-68.
  98. Boursier J, de L, V, Zarski JP, et al. Comparison of eight diagnostic algorithms for liver fibrosis in hepatitis C: new algorithms are more precise and entirely noninvasive. Hepatology. 2012;55:58-67.
  99. Lin ZH, Xin YN, Dong QJ, et al. Performance of the aspartate aminotransferase-to-platelet ratio index for the staging of hepatitis C-related fibrosis: an updated meta-analysis. Hepatology. 2011;53:726-736.
  100. Vallet-Pichard A, Mallet V, Nalpas B, et al. FIB-4: an inexpensive and accurate marker of fibrosis in HCV infection. Comparison with liver biopsy and fibrotest. Hepatology. 2007;46:32-36.
  101. Rossi E, Adams L, Prins A, et al. Validation of the FibroTest biochemical markers score in assessing liver fibrosis in hepatitis C patients. Clin Chem. 2003;49:450-454.
  102. Feld JJ, Liang TJ. Hepatitis C—identifying patients with progressive liver injury. Hepatology. 2006;43(2 suppl 1):S194-S206.
  103. Kanwal F, Kramer JR, Ilyas J, Duan Z, El-Serag HB. HCV genotype 3 is associated with an increased risk of cirrhosis and hepatocellular cancer in a national sample of U.S. Veterans with HCV. Hepatology. 2014;60:98-105.
  104. Singal AG, Volk ML, Jensen D, Di Bisceglie AM, Schoenfeld PS. A sustained viral response is associated with reduced liver-related morbidity and mortality in patients with hepatitis C virus. Clin Gastroenterol Hepatol. 2010;8:280-288.
  105. Iacobellis A, Siciliano M, Perri F, et al. Peginterferon alfa-2b and ribavirin in patients with hepatitis C virus and decompensated cirrhosis: a controlled study. J Hepatol. 2007;46:206-212.
  106. Everson GT. Treatment of chronic hepatitis C in patients with decompensated cirrhosis. Rev Gastroenterol Disord. 2004;4(suppl 1):S31-S38.
  107. Carrión JA, Navasa M, Forns X. Retransplantation in patients with hepatitis C recurrence after liver transplantation. J Hepatol. 2010;53:962-970.
  108. 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;149:649-659.
  109. World Health Organization. Guidelines for the screening, care and treatment of persons with hepatitis C infection: April 2016. Available at: http://www.who.int/hepatitis/publications/hepatitis-c-guidelines-2016/en/. Accessed May 15, 2019.
  110. Kohli A, Kapoor R, Sims Z, et al. Ledipasvir and sofosbuvir for hepatitis C genotype 4: a proof of concept phase 2a cohort study. Lancet Infect Dis. 2015;15:1049-1054.
  111. 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;373:2599-2607.
  112. Foster GR, Afdhal N, Roberts SK, et al. Sofosbuvir and velpatasvir for HCV genotype 2 and 3 infection. N Engl J Med. 2015;373:2608-2617.
  113. Curry MP, O’Leary JG, Bzowej N, et al. Sofosbuvir and velpatasvir for HCV in patients with decompensated cirrhosis. N Engl J Med. 2015;373:2618-2628. 
  114. Hézode C, Asselah T, Reddy KR, et al. Ombitasvir plus paritaprevir plus ritonavir with or without ribavirin in treatment-naive and treatment-experienced patients with genotype 4 chronic hepatitis C virus infection (PEARL-I): a randomised, open-label trial. Lancet. 2015;385:2502-2509.
  115. 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;370:1594-1603.
  116. 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;370:1604-1614.
  117. 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;370:1983-1992.
  118. 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;147:359-365.
  119. 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;370:1973-1982.
  120. Pockros PJ, Reddy KR, Mantry PS, et al. Efficacy of direct-acting antiviral combination for patients with hepatitis C virus genotype 1 infection and severe renal impairment or end-stage renal disease. Gastroenterology. 2016;150:1590-1598.
  121. Welzel TM, Asselah T, Dumas EO, et al. Ombitasvir, paritaprevir, and ritonavir plus dasabuvir for 8 weeks in previously untreated patients with hepatitis C virus genotype 1b infection without cirrhosis (GARNET): a single-arm, open-label, phase 3b trial. Lancet Gastroenterol Hepatol. 2017;2:494-500.
  122. Nelson DR, Cooper JN, Lalezari JP, et al. All-oral 12-week treatment with daclatasvir plus sofosbuvir in patients with hepatitis C virus genotype 3 infection: ALLY-3 phase III study. Hepatology. 2015;61:1127-1135.
  123. Leroy V, Angus P, Bronowicki JP, et al. Daclatasvir, sofosbuvir, and ribavirin for hepatitis C virus genotype 3 and advanced liver disease: A randomized phase III study (ALLY-3+). Hepatology. 2016;63:1430-1441.
  124. Zeuzem Z, 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.
  125. Brown A, Hézode C, Zuckerman E, et al. Efficacy and safety of 12 weeks of elbasvir ± grazoprevir ± ribavirin in participants with HCV genotype 2, 4, 5, or 6 infection: the C-SCAPE study. J Viral Hepat. 2018;25:457-464.
  126. Kwo P, Gane EJ, Peng CY, et al. Effectiveness of elbasvir and grazoprevir combination, with or without ribavirin, for treatment-experienced patients with chronic hepatitis C infection. Gastroenterology. 2017;152:164-175.
  127. Forns X, Gordon SC, Zuckerman E, et al. Grazoprevir and elbasvir plus ribavirin for chronic HCV genotype-1 infection after failure of combination therapy containing a direct-acting antiviral agent. J Hepatol. 2015;63:564-572.
  128. 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;62:32-36.
  129. Kwo PY, Poordad F, Asatryan A, et al. Glecaprevir and pibrentasvir yield high response rates in patients with HCV genotype 1-6 without cirrhosis. J Hepatol. 2017;67:263-271.
  130. Zeuzem S, Foster GR, Wang S, et al. Glecaprevir-pibrentasvir for 8 or 12 weeks in HCV genotype 1 or 3 infection. N Engl J Med. 2018;378:354-369.
  131. Asselah T, Kowdley KV, Zadeikis N, et al. Efficacy of glecaprevir/pibrentasvir for 8 or 12 weeks in patients with hepatitis C virus genotype 2, 4, 5, or 6 infection without cirrhosis. Clin Gastroenterol Hepatol. 2018;16:417-426.
  132. 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;62:79-86.
  133. 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;16:685-697.
  134. Forns X, Poordad F, Pedrosa M, et al. Ombitasvir/paritaprevir/r, dasabuvir and ribavirin for cirrhotic HCV patients with thrombocytopaenia and hypoalbuminaemia. Liver Int. 2015;35:2358-2362.
  135. Gane E, Poordad F, Wang S, et al. High efficacy of ABT-493 and ABT-530 treatment in patients with HCV genotype 1 or 3 infection and compensated cirrhosis. Gastroenterology. 2016;151:651-659.e1.
  136. Forns X, Lee SS, Valdes J, et al. Glecaprevir plus pibrentasvir for chronic hepatitis C virus genotype 1, 2, 4, 5, or 6 infection in adults with compensated cirrhosis (EXPEDITION-1): a single-arm, open-label, multicentre phase 3 trial. Lancet Infect Dis. 2017;17:1062-1068.
  137. Rong L, Dahari H, Ribeiro RM, Perelson AS. Rapid emergence of protease inhibitor resistance in hepatitis C virus. Sci Transl Med. 2010;2:30ra32.
  138. Sarrazin C, Zeuzem S. Resistance to direct antiviral agents in patients with hepatitis C virus infection. Gastroenterology. 2010;138:447-462.
  139. Sherman KE, Sulkowski MS, Zoulim F, et al. Follow-up of SVR durability and viral resistance in patients with chronic hepatitis C treated with telaprevir-based regimens: interim analysis of the EXTEND study. Program and Abstracts of the Annual Meeting of the American Association for the study of Liver Diseases; November 4-8, 2011; San Francisco, California. Abstract 248.
  140. Kieffer TL, De Meyer S, Bartels DJ, et al. Hepatitis C viral evolution in genotype 1 treatment-naive and treatment-experienced patients receiving telaprevir-based therapy in clinical trials. PLoS One. 2012;7:e34372.
  141. De Meyer S, Dierynck I, Ghys A, et al. Characterization of telaprevir treatment outcomes and resistance in patients with prior treatment failure: results from the realize trial. Hepatology. 2012;56:2106-2115.
  142. Barnard RJ, Howe JA, Ogert RA, et al. Analysis of boceprevir resistance associated amino acid variants (RAVs) in two phase 3 boceprevir clinical studies. Virology. 2013;444:329-336.
  143. Wyles DL, Gutierrez JA. Importance of HCV genotype 1 subtypes for drug resistance and response to therapy. J Viral Hepat. 2014;21:229-240.
  144. Sarrazin C, Reesink HW, Zeuzem S, et al. Retreatment with telaprevir/Peg-IFN/RBV after a short exposure to telaprevir in phase I studies: interim results from a phase IIIb rollover trial (C219). Program and abstracts of the Annual Meeting of the American Association for the Study of Liver Diseases; November 4-8, 2011; San Francisco, California. Abstract 35.
  145. 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;383:515-523.
  146. 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;61:1793-1797.
  147. Esteban R, Nyberg L, Lalezari J, et al. Successful retreatment with sofosbuvir-containing regimens for HCV genotype 2 or 3 infected patients who failed prior sofosbuvir plus ribavirin therapy. Program and abstracts of the 49th Annual Meeting of the European Association for the Study of the Liver; April 9-13, 2014; London, England. Abstract O8.
  148. Manns M, Pol S, Jacobson IM, et al. All-oral daclatasvir plus asunaprevir for hepatitis C virus genotype 1b: a multinational, phase 3, multicohort study. Lancet. 2014;384:1597-1605.
  149. Sarrazin C, Dvory-Sobol H, Svarovskaia ES, et al. Prevalence of resistance-associated substitutions in HCV NS5A, NS5B, or NS3 and outcomes of treatment with ledipasvir and sofosbuvir. Gastroenterology. 2016;151:501-512.
  150. Wyles D, Mangia A, Cheng W, et al. Long-term persistence of HCV NS5A resistance associated substitutions after treatment with the HCV NS5A inhibitor, ledipasvir, without sofosbuvir. Antivir Ther. 2017;[Epub ahead of print].
  151. Halfon P, Locarnini S. Hepatitis C virus resistance to protease inhibitors. J Hepatol. 2011;55:192-206.
  152. Lawitz E, Matusow G, DeJesus E, et al. Simeprevir plus sofosbuvir in patients with chronic hepatitis C virus genotype 1 infection and cirrhosis: a phase 3 study (OPTIMIST-2). Hepatology. 2016;64:360-369.
  153. Paolucci S, Fiorina L, Mariani B, et al. Naturally occurring resistance mutations to inhibitors of HCV NS5A region and NS5B polymerase in DAA treatment-naïve patients. Virol J. 2013;10:355.
  154. Ge D, Fellay J, Thompson AJ, et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature. 2009;461:399-401.
  155. Tanaka Y, Nishida N, Sugiyama M, et al. Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C. Nat Genet. 2009;41:1105-1109.
  156. Thomas DL, Thio CL, Martin MP, et al. Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature. 2009;461:798-801.
  157. Jacobson IM, Catlett I, Marcellin P, et al. Telaprevir substantially improved SVR rates across all IL28B genotypes in the ADVANCE trial. Program and abstracts of the 46th Annual Meeting of the European Association for the Study of the Liver; March 30 - April 3, 2011; Berlin, Germany. Abstract 1369.
  158. Poordad F, Bronowicki JP, Gordon SC, et al. Factors that predict response of patients with hepatitis C virus infection to boceprevir. Gastroenterology. 2012;143:608-618.
  159. Chen L, Borozan I, Feld J, et al. Hepatic gene expression discriminates responders and nonresponders in treatment of chronic hepatitis C viral infection. Gastroenterology. 2005;128:1437-1444.
  160. Feld JJ, Nanda S, Huang Y, et al. Hepatic gene expression during treatment with peginterferon and ribavirin: Identifying molecular pathways for treatment response. Hepatology. 2007;46:1548-1563.
  161. Sarasin-Filipowicz M, Oakeley EJ, Duong FH, et al. Interferon signaling and treatment outcome in chronic hepatitis C. Proc Natl Acad Sci U S A. 2008;105:7034-7039.
  162. Honda M, Sakai A, Yamashita T, et al. Hepatic ISG expression is associated with genetic variation in interleukin 28B and the outcome of IFN therapy for chronic hepatitis C. Gastroenterology. 2010;139:499-509.
  163. Lagging M, Romero AI, Westin J, et al. IP-10 predicts viral response and therapeutic outcome in difficult-to-treat patients with HCV genotype 1 infection. Hepatology. 2006;44:1617-1625.
  164. Diago M, Castellano G, García-Samaniego J, et al. Association of pretreatment serum interferon gamma inducible protein 10 levels with sustained virological response to peginterferon plus ribavirin therapy in genotype 1 infected patients with chronic hepatitis C. Gut. 2006;55:374-379.
  165. Romero AI, Lagging M, Westin J, et al. Interferon (IFN)-gamma-inducible protein-10: association with histological results, viral kinetics, and outcome during treatment with pegylated IFN-alpha 2a and ribavirin for chronic hepatitis C virus infection. J Infect Dis. 2006;194:895-903.
  166. Darling JM, Aerssens J, Fanning G, et al. Quantitation of pretreatment serum interferon-γ-inducible protein-10 improves the predictive value of an IL28B gene polymorphism for hepatitis C treatment response. Hepatology. 2011;53:14-22.
  167. Eslam M, Aparcero R, Kawaguchi T, et al. Meta-analysis: insulin resistance and sustained virological response in hepatitis C. Aliment Pharmacol Ther. 2011;34:297-305.
  168. Fried MW, Jensen DM, Rodriguez-Torres M, et al. Improved outcomes in patients with hepatitis C with difficult-to-treat characteristics: randomized study of higher doses of peginterferon alpha-2a and ribavirin. Hepatology. 2008;48:1033-1043.
  169. Pattullo V, Heathcote J. Hepatitis C and diabetes: one treatment for two diseases? Liver Int. 2010;30:356-364.
  170. Romero-Gómez M, Diago M, Andrade RJ, et al. Treatment of insulin resistance with metformin in naive genotype 1 chronic hepatitis C patients receiving peginterferon alfa-2a plus ribavirin. Hepatology. 2009;50:1702-1708.
  171. Harrison SA, Hamzeh FM, Han J, Pandya PK, Sheikh MY, Vierling JM. Chronic hepatitis C genotype 1 patients with insulin resistance treated with pioglitazone and peginterferon alpha-2a plus ribavirin. Hepatology. 2012;56:464-473.
  172. Serfaty L, Forns X, Goeser T, et al. Insulin resistance and response to telaprevir plus peginterferon α and ribavirin in treatment-naive patients infected with HCV genotype 1. Gut. 2012;61:1473-1480.
  173. Freedman ND, Curto TM, Lindsay KL, et al. Coffee consumption is associated with response to peginterferon and ribavirin therapy in patients with chronic hepatitis C. Gastroenterology. 2011;140:1961-1969.
  174. Abu-Mouch S, Fireman Z, Jarchovsky J, et al. Vitamin D supplementation improves sustained virologic response in chronic hepatitis C (genotype 1)-naive patients. World J Gastroenterol. 2011;17:5184-5190.
  175. Feld JJ, Modi AA, El-Diwany R, et al. S-adenosyl methionine improves early viral responses and interferon-stimulated gene induction in hepatitis C nonresponders. Gastroenterology. 2011;140:830-839.
  176. Poordad F, McCone J Jr, Bacon BR, et al. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med. 2011;364:1195-1206.
  177. Jacobson IM, McHutchison JG, Dusheiko G, et al. Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med. 2011;364:2405-2416.
  178. Mangia A, Thompson AJ, Santoro R, et al. Limited use of interleukin 28B in the setting of response-guided treatment with detailed on-treatment virological monitoring. Hepatology. 2011;54:772-780.
  179. Thompson AJ, Muir AJ, Sulkowski MS, et al. Interleukin-28B polymorphism improves viral kinetics and is the strongest pretreatment predictor of sustained virologic response in genotype 1 hepatitis C virus. Gastroenterology. 2010;139:120-129.
  180. US Food and Drug Administration. Boceprevir. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/202258s016lbl.pdf. Accessed May 15, 2019.
  181. US Food and Drug Administration. Telaprevir. Available at: http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=201917. Accessed May 15, 2019.
  182. Kowdley KV, Colombo M, Zadeikis N, et al. ENDURANCE-2: safety and efficacy of ABT-493/ABT-530 in hepatitis C virus genotype 2-infected patients without cirrhosis, a randomized, double-blind, placebo-controlled study. Program and abstracts of the 2016 Annual Meeting of the American Association for the Study of Liver Diseases; November 11-15, 2016; Boston, Massachusetts. Abstract 73.
  183. Asselah T, Hezode C, Zadeikis N, et al. ENDURANCE-4: efficacy and safety of ABT-493/ABT-530 treatment in patients with chronic HCV genotype 4, 5, or 6 infection. Program and abstracts of the 2016 Annual Meeting of the American Association for the Study of Liver Diseases; November 11-15, 2016; Boston, Massachusetts. Abstract 114.
  184. Martin TC, Martin NK, Hickman M, et al. Hepatitis C virus reinfection incidence and treatment outcome among HIV-positive MSM. AIDS. 2013;27:2551-2557.
  185. Sacks-Davis R, Aitken CK, Higgs P, et al. High rates of hepatitis C virus reinfection and spontaneous clearance of reinfection in people who inject drugs: a prospective cohort study. PLoS One. 2013;8:e80216.
  186. Bruno S, Crosignani A, Facciotto C, et al. Sustained virologic response prevents the development of esophageal varices in compensated, Child-Pugh class A hepatitis C virus-induced cirrhosis. A 12-year prospective follow-up study. Hepatology. 2010;51:2069-2076.
  187. Simmons B, Saleem J, Hill A, et al. Risk of late relapse or reinfection with hepatitis C virus after achieving a sustained virological response: a systematic review and meta-analysis. Clin Infect Dis. 2016;62:683-694.
  188. Dore G, Grebely J, Altice F, et al. Hepatitis C virus reinfection and injecting risk behavior following elbasvir/grazoprevir treatment in participants on opiate agonist therapy: C-EDGE Co-STAR Part B. Program and abstracts of the 2017 Annual Meeting of the American Association for the Study of Liver Diseases; October 20-24, 2017; Washington, DC. Abstract 195.
  189. Ingiliz P, Martin TC, Rodger A, et al. HCV reinfection incidence and spontaneous clearance rates in HIV-positive men who have sex with men in Western Europe. J Hepatol. 2017;66:282-287.
  190. Falade-Nwulia O, Sulkowski M. The HCV care continuum does not end with cure: A call to arms for the prevention of reinfection. J Hepatol. 2017;66:267-269.
  191. Midgard H, Weir A, Palmateer N, et al. HCV epidemiology in high-risk groups and the risk of reinfection. J Hepatol. 2016;65(1 suppl):S33-S45.
  192. Martin NK, Skaathun B, Vickerman P, et al. Modeling combination HCV prevention among HIV-infected men who have sex with men and people who inject drugs. AIDS Rev. 2017;19:97-104.
  193. Maheshwari A, Ray S, Thuluvath PJ. Acute hepatitis C. Lancet. 2008;372:321-332.
  194. Wang CC, Krantz E, Klarquist J, et al. Acute hepatitis C in a contemporary US cohort: modes of acquisition and factors influencing viral clearance. J Infect Dis. 2007;196:1474-1482.
  195. Wietzke-Braun P, Manhardt LB, Rosenberger A, Uy A, Ramadori G, Mihm S. Spontaneous elimination of hepatitis C virus infection: a retrospective study on demographic, clinical, and serological correlates. World J Gastroenterol. 2007;13:4224-4229.
  196. Gerlach JT, Diepolder HM, Zachoval R, et al. Acute hepatitis C: high rate of both spontaneous and treatment-induced viral clearance. Gastroenterology. 2003;125:80-88.
  197. Hofer H, Watkins-Riedel T, Janata O, et al. Spontaneous viral clearance in patients with acute hepatitis C can be predicted by repeated measurements of serum viral load. Hepatology. 2003;37:60-64.
  198. Tillmann HL, Thompson AJ, Patel K, et al. A polymorphism near IL28B is associated with spontaneous clearance of acute hepatitis C virus and jaundice. Gastroenterology. 2010;139:1586-1592.
  199. Grebely J, Page K, Sacks-Davis R, et al. The effects of female sex, viral genotype, and IL28B genotype on spontaneous clearance of acute hepatitis C virus infection. Hepatology. 2014;59:109-120.
  200. Thomson EC, Fleming VM, Main J, et al. Predicting spontaneous clearance of acute hepatitis C virus in a large cohort of HIV-1-infected men. Gut. 2011;60:837-845.
  201. Licata A, Di Bona D, Schepis F, Shahied L, Craxí A, Cammà C. When and how to treat acute hepatitis C? J Hepatol. 2003;39:1056-1062.
  202. Vogel W, Graziadei I, Umlauft F, et al. High-dose interferon-alpha2b treatment prevents chronicity in acute hepatitis C: a pilot study. Dig Dis Sci. 1996;41(12 suppl):81S-85S.
  203. Jaeckel E, Cornberg M, Wedemeyer H, et al. Treatment of acute hepatitis C with interferon alfa-2b. N Engl J Med. 2001;345:1452-1457.
  204. Nomura H, Sou S, Tanimoto H, et al. Short-term interferon-alfa therapy for acute hepatitis C: a randomized controlled trial. Hepatology. 2004;39:1213-1219.
  205. Wiegand J, Buggisch P, Boecher W, et al. Early monotherapy with pegylated interferon alpha-2b for acute hepatitis C infection: the HEP-NET acute-HCV-II study. Hepatology. 2006;43:250-256.
  206. De Rosa FG, Bargiacchi O, Audagnotto S, et al. Dose-dependent and genotype-independent sustained virological response of a 12 week pegylated interferon alpha-2b treatment for acute hepatitis C. J Antimicrob Chemother. 2006;57:360-363.
  207. Calleri G, Cariti G, Gaiottino F, et al. A short course of pegylated interferon-alpha in acute HCV hepatitis. J Viral Hepat. 2007;14:116-121.
  208. Mangia A, Santoro R, Copetti M, et al. Treatment optimization and prediction of HCV clearance in patients with acute HCV infection. J Hepatol. 2013;59:221-228.
Back Next

Leaving the CCO site

You are now leaving the CCO site. The new destination site may have different terms of use and privacy policy.

Continue

Cookie Settings