Original Research17 March 2015
    Author, Article and Disclosure Information

    New regimens for hepatitis C virus (HCV) have shorter treatment durations and increased rates of sustained virologic response compared with existing therapies but are extremely expensive.


    To evaluate the cost-effectiveness of these treatments under different assumptions about their price and efficacy.


    Discrete-event simulation.

    Data Sources:

    Published literature.

    Target Population:

    Treatment-naive patients infected with chronic HCV genotype 1, 2, or 3.

    Time Horizon:





    Usual care (boceprevir–ribavirin–pegylated interferon [PEG]) was compared with sofosbuvir–ribavirin–PEG and 3 PEG-free regimens: sofosbuvir–simeprevir, sofosbuvir–daclatasvir, and sofosbuvir–ledipasvir. For genotypes 2 and 3, usual care (ribavirin–PEG) was compared with sofosbuvir–ribavirin, sofosbuvir–daclatasvir, and sofosbuvir–ledipasvir–ribavirin (genotype 3 only).

    Outcome Measures:

    Discounted costs (in 2014 U.S. dollars), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios.

    Results of Base-Case Analysis:

    Assuming sofosbuvir, simeprevir, daclatasvir, and ledipasvir cost $7000, $5500, $5500, and $875 per week, respectively, sofosbuvir–ledipasvir was cost-effective for genotype 1 and cost $12 825 more per QALY than usual care. For genotype 2, sofosbuvir–ribavirin and sofosbuvir–daclatasvir cost $110 000 and $691 000 per QALY, respectively. For genotype 3, sofosbuvir–ledipasvir–ribavirin cost $73 000 per QALY, sofosbuvir–ribavirin was more costly and less effective than usual care, and sofosbuvir–daclatasvir cost more than $396 000 per QALY at assumed prices.

    Results of Sensitivity Analysis:

    Sofosbuvir–ledipasvir was the optimal strategy in most simulations for genotype 1 and would be cost-saving if sofosbuvir cost less than $5500. For genotype 2, sofosbuvir–ribavirin–PEG would be cost-saving if sofosbuvir cost less than $2250 per week. For genotype 3, sofosbuvir–ledipasvir–ribavirin would be cost-saving if sofosbuvir cost less than $1500 per week.


    Data are lacking on real-world effectiveness of new treatments and some prices.


    From a societal perspective, novel treatments for HCV are cost-effective compared with usual care for genotype 1 and probably genotype 3 but not for genotype 2.

    Primary Funding Source:

    CVS Health.


    • 1. Yee HS Chang MF Pocha C Lim J Ross D Morgan TR et alDepartment of Veterans Affairs Hepatitis C Resource Center ProgramUpdate on the management and treatment of hepatitis C virus infection: recommendations from the Department of Veterans Affairs Hepatitis C Resource Center Program and the National Hepatitis C Program Office. Am J Gastroenterol2012;107:669-89. [PMID: 22525303] doi:10.1038/ajg.2012.48 CrossrefMedlineGoogle Scholar
    • 2. U.S. Food and Drug Administration approves Gilead's Sovaldi (sofosbuvir) for the treatment of chronic hepatitis C [press release]. Foster City, CA: Gilead Sciences; 6 December 2013. Google Scholar
    • 3. Lawitz E Mangia A Wyles D Rodriguez-Torres M Hassanein T Gordon SC et alSofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med2013;368:1878-87. [PMID: 23607594] doi:10.1056/NEJMoa1214853 CrossrefMedlineGoogle Scholar
    • 4. Osinusi A Meissner EG Lee YJ Bon D Heytens L Nelson A et alSofosbuvir and ribavirin for hepatitis C genotype 1 in patients with unfavorable treatment characteristics: a randomized clinical trial. JAMA2013;310:804-11. [PMID: 23982366] doi:10.1001/jama.2013.109309 CrossrefMedlineGoogle Scholar
    • 5. Zeuzem S Dusheiko GM Salupere R Mangia A Flisiak R Hyland RH et alVALENCE InvestigatorsSofosbuvir and ribavirin in HCV genotypes 2 and 3. N Engl J Med2014;370:1993-2001. [PMID: 24795201] doi:10.1056/NEJMoa1316145 CrossrefMedlineGoogle Scholar
    • 6. Jacobson IM Gordon SC Kowdley KV Yoshida EM Rodriguez-Torres M Sulkowski MS et alPOSITRON StudySofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. N Engl J Med2013;368:1867-77. [PMID: 23607593] doi:10.1056/NEJMoa1214854 CrossrefMedlineGoogle Scholar
    • 7. Lawitz E Sulkowski MS Ghalib R Rodriguez-Torres M Younossi ZM Corregidor A et alSimeprevir 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. Lancet2014;384:1756-65. [PMID: 25078309] doi:10.1016/S0140-6736(14)61036-9 CrossrefMedlineGoogle Scholar
    • 8. Jacobson I, Ghalib R, Rodriguez-Torres Mea. SVR results of a once-daily regimen of simeprevir (SMV, TMC435) plus sofosbuvir (SOF, GS-7977) with or without ribavirin in cirrhotic and non-cirrhotic HCV genotype 1 treatment-naïive and prior null responder patients: the COSMOS study [Abstract]. Presented at 64th Annual Meeting of the American Association for the Study of Liver Diseases, Washington, DC, 1–5 November 2013. Abstract no. LB3. Google Scholar
    • 9. Sulkowski MS Gardiner DF Rodriguez-Torres M Reddy KR Hassanein T Jacobson I et alAI444040 Study GroupDaclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection. N Engl J Med2014;370:211-21. [PMID: 24428467] doi:10.1056/NEJMoa1306218 CrossrefMedlineGoogle Scholar
    • 10. Afdhal N Zeuzem S Kwo P Chojkier M Gitlin N Puoti M et alION-1 InvestigatorsLedipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med2014;370:1889-98. [PMID: 24725239] doi:10.1056/NEJMoa1402454 CrossrefMedlineGoogle Scholar
    • 11. Kowdley KV Gordon SC Reddy KR Rossaro L Bernstein DE Lawitz E et alION-3 InvestigatorsLedipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. N Engl J Med2014;370:1879-88. [PMID: 24720702] doi:10.1056/NEJMoa1402355 CrossrefMedlineGoogle Scholar
    • 12. Lawitz E Poordad FF Pang PS Hyland RH Ding X Mo H et alSofosbuvir 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. Lancet2014;383:515-23. [PMID: 24209977] doi:10.1016/S0140-6736(13)62121-2 CrossrefMedlineGoogle Scholar
    • 13. Gilead announces phase 2 results for two investigational all-oral sofosbuvir-based regimens for the treatment of chronic hepatitis C [press release]. London: Gilead Sciences; 10 April 2014. Google Scholar
    • 14. Armstrong GL Wasley A Simard EP McQuillan GM Kuhnert WL Alter MJ The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann Intern Med2006;144:705-14. [PMID: 16702586] LinkGoogle Scholar
    • 15. Brennan T Shrank W New expensive treatments for hepatitis C infection. JAMA2014;312:593-4. [PMID: 25038617] doi:10.1001/jama.2014.8897 CrossrefMedlineGoogle Scholar
    • 16. Owens GM. Hepatitis C: new treatments emerge in 2014 that will have profound implications for payers. Am J Manag Care. 31 March 2014. Accessed at www.ajmc.com/payer-perspectives/0314/-Hepatitis-C-New-Treatments-Emerge-in-2014-That-Will-Have-Profound-Implications-for-Payers on 23 January 2015. Google Scholar
    • 17. Caro JJ Briggs AH Siebert U Kuntz KM ISPOR-SMDM Modeling Good Research Practices Task ForceModeling good research practices—overview: a report of the ISPOR-SMDM Modeling Good Research Practices Task Force-1. Med Decis Making2012;32:667-77. [PMID: 22990082] CrossrefMedlineGoogle Scholar
    • 18. Caro JJ Möller J Getsios D Discrete event simulation: the preferred technique for health economic evaluations? Value Health2010;13:1056-60. [PMID: 20825626] doi:10.1111/j.1524-4733.2010.00775.x CrossrefMedlineGoogle Scholar
    • 19. Gold MR Siegel JE Russell LB Weinstein MC Cost-Effectiveness in Health and Medicine. New York: Oxford Univ Pr; 1996. Google Scholar
    • 20. Karnon J Stahl J Brennan A Caro JJ Mar J Möller J Modeling using discrete event simulation: a report of the ISPOR-SMDM Modeling Good Research Practices Task Force-4. Med Decis Making2012;32:701-11. [PMID: 22990085] CrossrefMedlineGoogle Scholar
    • 21. Poordad F McCone J Jr Bacon BR Bruno S Manns MP Sulkowski MS et alSPRINT-2 InvestigatorsBoceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med2011;364:1195-206. [PMID: 21449783] doi:10.1056/NEJMoa1010494 CrossrefMedlineGoogle Scholar
    • 22. Fried MW Shiffman ML Reddy KR Smith C Marinos G Gonçales FL Jr et alPeginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med2002;347:975-82. [PMID: 12324553] CrossrefMedlineGoogle Scholar
    • 23. Gane EJ Stedman CA Hyland RH Ding X Svarovskaia E Symonds WT et alNucleotide polymerase inhibitor sofosbuvir plus ribavirin for hepatitis C. N Engl J Med2013;368:34-44. [PMID: 23281974] doi:10.1056/NEJMoa1208953 CrossrefMedlineGoogle Scholar
    • 24. Thompson AJ Muir AJ Sulkowski MS Ge D Fellay J Shianna KV et alInterleukin-28B polymorphism improves viral kinetics and is the strongest pretreatment predictor of sustained virologic response in genotype 1 hepatitis C virus. Gastroenterology2010;139:120-9. [PMID: 20399780] doi:10.1053/j.gastro.2010.04.013 CrossrefMedlineGoogle Scholar
    • 25. McHutchison JG Lawitz EJ Shiffman ML Muir AJ Galler GW McCone J et alIDEAL Study TeamPeginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med2009;361:580-93. [PMID: 19625712] doi:10.1056/NEJMoa0808010 CrossrefMedlineGoogle Scholar
    • 26. Holmes JA Desmond PV Thompson AJ Does IL28B genotyping still have a role in the era of direct-acting antiviral therapy for chronic hepatitis C infection? J Viral Hepat2012;19:677-84. [PMID: 22967098] doi:10.1111/jvh.12003 CrossrefMedlineGoogle Scholar
    • 27. Anand BS Currie S Dieperink E Bini EJ Shen H Ho SB et alVA-HCV-001 Study GroupAlcohol use and treatment of hepatitis C virus: results of a national multicenter study. Gastroenterology2006;130:1607-16. [PMID: 16697724] CrossrefMedlineGoogle Scholar
    • 28. Russell M Pauly MP Moore CD Chia C Dorrell J Cunanan RJ et alThe impact of lifetime alcohol use on hepatitis C treatment outcomes in privately insured members of an integrated health care plan. Hepatology2012;56:1223-30. [PMID: 22488513] doi:10.1002/hep.25755 CrossrefMedlineGoogle Scholar
    • 29. Denniston MM Jiles RB Drobeniuc J Klevens RM Ward JW McQuillan GM et alChronic hepatitis C virus infection in the United States, National Health and Nutrition Examination Survey 2003 to 2010. Ann Intern Med2014;160:293-300. [PMID: 24737271] doi:10.7326/M13-1133 LinkGoogle Scholar
    • 30. Poynard T Bedossa P Opolon P Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups. Lancet1997;349:825-32. [PMID: 9121257] CrossrefMedlineGoogle Scholar
    • 31. Freeman AJ Dore GJ Law MG Thorpe M Von Overbeck J Lloyd AR et alEstimating progression to cirrhosis in chronic hepatitis C virus infection. Hepatology2001;34:809-16. [PMID: 11584380] CrossrefMedlineGoogle Scholar
    • 32. Thein HH Yi Q Dore GJ Krahn MD Estimation of stage-specific fibrosis progression rates in chronic hepatitis C virus infection: a meta-analysis and meta-regression. Hepatology2008;48:418-31. [PMID: 18563841] doi:10.1002/hep.22375 CrossrefMedlineGoogle Scholar
    • 33. Liu S Cipriano LE Holodniy M Owens DK Goldhaber-Fiebert JDNew protease inhibitors for the treatment of chronic hepatitis C: a cost-effectiveness analysis. Ann Intern Med2012;156:279-90. [PMID: 22351713] doi:10.7326/0003-4819-156-4-201202210-00005 LinkGoogle Scholar
    • 34. Salomon JA Weinstein MC Hammitt JK Goldie SJ Empirically calibrated model of hepatitis C virus infection in the United States. Am J Epidemiol2002;156:761-73. [PMID: 12370165] CrossrefMedlineGoogle Scholar
    • 35. Salomon JA Weinstein MC Hammitt JK Goldie SJ Cost-effectiveness of treatment for chronic hepatitis C infection in an evolving patient population. JAMA2003;290:228-37. [PMID: 12851278] CrossrefMedlineGoogle Scholar
    • 36. Arias E National Vital Statistics Reports. Vol. 61. No. 3. Hyattsville, MD: U.S. Department of Health and Human Services; 2012. Google Scholar
    • 37. Sullivan PW Ghushchyan V Preference-Based EQ-5D index scores for chronic conditions in the United States. Med Decis Making2006;26:410-20. [PMID: 16855129] CrossrefMedlineGoogle Scholar
    • 38. McLernon DJ Dillon J Donnan PT Health-state utilities in liver disease: a systematic review. Med Decis Making2008;28:582-92. [PMID: 18424560] doi:10.1177/0272989X08315240 CrossrefMedlineGoogle Scholar
    • 39. McAdam-Marx C McGarry LJ Hane CA Biskupiak J Deniz B Brixner DI All-cause and incremental per patient per year cost associated with chronic hepatitis C virus and associated liver complications in the United States: a managed care perspective. J Manag Care Pharm2011;17:531-46. [PMID: 21870894] CrossrefMedlineGoogle Scholar
    • 40. McCombs JS Yuan Y Shin J Saab S Economic burden associated with patients diagnosed with hepatitis C. Clin Ther2011;33:1268-80. [PMID: 21840056] doi:10.1016/j.clinthera.2011.07.008 CrossrefMedlineGoogle Scholar
    • 41. Ryan B. FDA approves Gilead's hep C drug Harvoni (ledipasvir/sofosbuvir). Hep Magazine. 10 October 2014. Google Scholar
    • 42. Bedossa P Poynard T An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group. Hepatology1996;24:289-93. [PMID: 8690394] CrossrefMedlineGoogle Scholar
    • 43. Brown RS Hepatitis C and liver transplantation. Nature2005;436:973-8. [PMID: 16107838] CrossrefMedlineGoogle Scholar
    • 44. Davis KL Mitra D Medjedovic J Beam C Rustgi V Direct economic burden of chronic hepatitis C virus in a United States managed care population. J Clin Gastroenterol2011;45:e17-24. [PMID: 20628308] doi:10.1097/MCG.0b013e3181e12c09 CrossrefMedlineGoogle Scholar
    • 45. Gordon SC Pockros PJ Terrault NA Hoop RS Buikema A Nerenz D et alImpact of disease severity on healthcare costs in patients with chronic hepatitis C (CHC) virus infection. Hepatology2012;56:1651-60. [PMID: 22610658] doi:10.1002/hep.25842 CrossrefMedlineGoogle Scholar
    • 46. Solomon M Bonafede M Pan K Wilson K Beam C Chakravarti P et alDirect medical care costs among pegylated interferon plus ribavirin-treated and untreated chronic hepatitis C patients. Dig Dis Sci2011;56:3024-31. [PMID: 21717127] doi:10.1007/s10620-011-1802-z CrossrefMedlineGoogle Scholar
    • 47. Chan K Lai MN Groessl EJ Hanchate AD Wong JB Clark JA et alCost effectiveness of direct-acting antiviral therapy for treatment-naive patients with chronic HCV genotype 1 infection in the Veterans Health Administration. Clin Gastroenterol Hepatol2013;11:1503-10. [PMID: 23707354] doi:10.1016/j.cgh.2013.05.014 CrossrefMedlineGoogle Scholar
    • 48. Ferrante SA Chhatwal J Brass CA ElKhoury AC Poordad F Bronowicki JP et alBoceprevir for previously untreated patients with chronic hepatitis C genotype 1 infection: a US-based cost-effectiveness modeling study. BMC Infect Dis2013;13:190. [PMID: 23621902] doi:10.1186/1471-2334-13-190 CrossrefMedlineGoogle Scholar
    • 49. CPI inflation calculator. Bureau of Labor Statistics. 2014. Accessed at www.bls.gov/data/inflation_calculator.htm on 24 January 2015. Google Scholar
    • 50. Claxton K Sculpher M McCabe C Briggs A Akehurst R Buxton M et alProbabilistic sensitivity analysis for NICE technology assessment: not an optional extra. Health Econ2005;14:339-47. [PMID: 15736142] CrossrefMedlineGoogle Scholar
    • 51. Briggs AH Handling uncertainty in cost-effectiveness models. Pharmacoeconomics2000;17:479-500. [PMID: 10977389] CrossrefMedlineGoogle Scholar
    • 52. Spiegelhalter DJ Best NG Bayesian approaches to multiple sources of evidence and uncertainty in complex cost-effectiveness modelling. Stat Med2003;22:3687-709. [PMID: 14652869] CrossrefMedlineGoogle Scholar
    • 53. FDA approves Viekira Pak to treat hepatitis C [press release]. Silver Spring, MD: U.S. Food and Drug Administration; 19 December 2014. Accessed at www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm427530.htm on 22 December 2014. Google Scholar