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Mediators of Inflammation
Volume 2016 (2016), Article ID 6841628, 11 pages
http://dx.doi.org/10.1155/2016/6841628
Review Article

Recent Advances in Antiviral Therapy for Chronic Hepatitis C

Department of Hepatology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan

Received 9 June 2015; Accepted 6 January 2016

Academic Editor: Carolina T. Piñeiro

Copyright © 2016 Akihiro Tamori et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. B. L. Pearlman, “Protease inhibitors for the treatment of chronic hepatitis C genotype-1 infection: the new standard of care,” The Lancet Infectious Diseases, vol. 12, no. 9, pp. 717–728, 2012. View at Publisher · View at Google Scholar · View at Scopus
  2. J. G. McHutchison, M. Manns, K. Patel et al., “Adherence to combination therapy enhances sustained response in genotype-1-infected patients with chronic hepatitis C,” Gastroenterology, vol. 123, no. 4, pp. 1061–1069, 2002. View at Publisher · View at Google Scholar · View at Scopus
  3. N. Coppola, M. Pisaturo, G. Tonziello, C. Sagnelli, E. Sagnelli, and I. F. Angelillo, “Efficacy of pegylated interferon α-2a and α-2b in patients with genotype 1 chronic hepatitis C: a meta-analysis,” BMC Infectious Diseases, vol. 12, article 357, 2012. View at Publisher · View at Google Scholar · View at Scopus
  4. A. Tamori, K. Kioka, O. Kurai et al., “Favorable factors for re-treatment with pegylated interferon α2a plus ribavirin in patients with high viral loads of genotype 1 hepatitis C virus,” Hepatology Research, vol. 41, no. 12, pp. 1169–1177, 2011. View at Publisher · View at Google Scholar · View at Scopus
  5. S. Nishiguchi, H. Enomoto, N. Aizawa et al., “Relevance of the core 70 and IL-28B polymorphism and response-guided therapy of peginterferon alfa-2a ± ribavirin for chronic hepatitis C of genotype 1b: a multicenter randomized trial, ReGIT-J study,” Journal of Gastroenterology, vol. 49, no. 3, pp. 492–501, 2014. View at Publisher · View at Google Scholar · View at Scopus
  6. T. Oze, N. Hiramatsu, T. Yakushijin et al., “Using early viral kinetics to predict antiviral outcome in response-guided pegylated interferon plus ribavirin therapy among patients with hepatitis C virus genotype 1,” Journal of Gastroenterology, vol. 49, no. 4, pp. 737–747, 2014. View at Publisher · View at Google Scholar · View at Scopus
  7. H. Hai, A. Tamori, M. Enomoto et al., “Relationship between inosine triphosphate genotype and outcome of extended therapy in hepatitis C virus patients with a late viral response to pegylated-interferon and ribavirin,” Journal of Gastroenterology and Hepatology, vol. 29, no. 1, pp. 201–207, 2014. View at Publisher · View at Google Scholar · View at Scopus
  8. J. G. McHutchison, M. P. Manns, A. J. Muir et al., “Telaprevir for previously treated chronic HCV infection,” The New England Journal of Medicine, vol. 362, no. 14, pp. 1292–1303, 2010. View at Publisher · View at Google Scholar · View at Scopus
  9. I. M. Jacobson, J. G. McHutchison, G. Dusheiko et al., “Telaprevir for previously untreated chronic hepatitis C virus infection,” The New England Journal of Medicine, vol. 364, no. 25, pp. 2405–2416, 2011. View at Publisher · View at Google Scholar · View at Scopus
  10. S. Zeuzem, P. Andreone, S. Pol et al., “Telaprevir for retreatment of HCV infection,” The New England Journal of Medicine, vol. 364, no. 25, pp. 2417–2428, 2011. View at Publisher · View at Google Scholar · View at Scopus
  11. I. M. Jacobson, P. Marcellin, S. Zeuzem et al., “Refinement of stopping rules during treatment of hepatitis C genotype 1 infection with boceprevir and peginterferon/ribavirin,” Hepatology, vol. 56, no. 2, pp. 567–575, 2012. View at Publisher · View at Google Scholar · View at Scopus
  12. “Recommendation for testing, managing, and treating hepatitis C,” AASLD, 2014, http://www.hcvguidelines.org.
  13. Clinical Practice Guidelines, “EASL recommendation on treatment of hepatitis C 2015. European Association for the Study of the Liver,” Journal of Hepatology, vol. 63, no. 1, pp. 199–236, 2015. View at Publisher · View at Google Scholar
  14. T. Asselah and P. Marcellin, “Direct acting antivirals for the treatment of chronic hepatitis C: one pill a day for tomorrow,” Liver International, vol. 32, no. 1, pp. 88–102, 2012. View at Publisher · View at Google Scholar · View at Scopus
  15. R. Bartenschlager, V. Lohmann, and F. Penin, “The molecular and structural basis of advanced antiviral therapy for hepatitis C virus infection,” Nature Reviews Microbiology, vol. 11, no. 7, pp. 482–496, 2013. View at Publisher · View at Google Scholar · View at Scopus
  16. J. Vermehren and C. Sarrazin, “The role of resistance in HCV treatment,” Best Practice and Research: Clinical Gastroenterology, vol. 26, no. 4, pp. 487–503, 2012. View at Publisher · View at Google Scholar · View at Scopus
  17. O. Lenz, T. Verbinnen, T.-I. Lin et al., “In vitro resistance profile of the hepatitis C virus NS3/4A protease inhibitor TMC435,” Antimicrobial Agents and Chemotherapy, vol. 54, no. 5, pp. 1878–1887, 2010. View at Publisher · View at Google Scholar · View at Scopus
  18. C. Moreno, T. Berg, T. Tanwandee et al., “Antiviral activity of TMC435 monotherapy in patients infected with HCV genotypes 2-6: TMC435-C202, a phase IIa, open-label study,” Journal of Hepatology, vol. 56, no. 6, pp. 1247–1253, 2012. View at Publisher · View at Google Scholar · View at Scopus
  19. I. Gentile, A. R. Buonomo, E. Zappulo et al., “Asunaprevir, a protease inhibitor for the treatment of hepatitis C infection,” Therapeutics and Clinical Risk Management, vol. 10, no. 1, pp. 493–504, 2014. View at Publisher · View at Google Scholar · View at Scopus
  20. V. Summa, S. W. Ludmerer, J. A. McCauley et al., “MK-5172, a selective inhibitor of hepatitis C virus NS3/4a protease with broad activity across genotypes and resistant variants,” Antimicrobial Agents and Chemotherapy, vol. 56, no. 8, pp. 4161–4171, 2012. View at Publisher · View at Google Scholar
  21. A. De Luca, C. Bianco, and B. Rossetti, “Treatment of HCV infection with the novel NS3/4A protease inhibitors,” Current Opinion in Pharmacology, vol. 18, pp. 9–17, 2014. View at Publisher · View at Google Scholar · View at Scopus
  22. M. Gao, R. E. Nettles, M. Belema et al., “Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect,” Nature, vol. 465, no. 7294, pp. 96–100, 2010. View at Publisher · View at Google Scholar · View at Scopus
  23. J. J. Kohler, J. H. Nettles, F. Amblard et al., “Approaches to hepatitis C treatment and cure using NS5A inhibitors,” Infection and Drug Resistance, vol. 7, pp. 41–56, 2014. View at Publisher · View at Google Scholar · View at Scopus
  24. T. C. Appleby, J. K. Perry, E. Murakami et al., “Structural basis for RNA replication by the hepatitis C virus polymerase,” Science, vol. 347, no. 6223, pp. 771–775, 2015. View at Publisher · View at Google Scholar · View at Scopus
  25. M. J. Sofia, D. Bao, W. Chang et al., “Discovery of a luoro-2′-β-C-methyluridine nucleotide prodrug (PSI-7977) for the treatment of hepatitis C virus,” Journal of Medicinal Chemistry, vol. 53, no. 19, pp. 7202–7218, 2010. View at Publisher · View at Google Scholar · View at Scopus
  26. T. McQuaid, C. Savini, and S. Seyedkazemi, “Sofosbuvir, a significant paradigm change in HCV treatment,” Journal of Clinical and Translational Hepatology, vol. 3, no. 1, pp. 27–35, 2015. View at Publisher · View at Google Scholar
  27. F. Poordad, J. McCone Jr., B. R. Bacon et al., “Boceprevir for untreated chronic HCV genotype 1 infection,” The New England Journal of Medicine, vol. 364, no. 13, pp. 1195–1206, 2011. View at Publisher · View at Google Scholar · View at Scopus
  28. B. R. Bacon, S. C. Gordon, E. Lawitz et al., “Boceprevir for previously treated chronic HCV genotype 1 infection,” The New England Journal of Medicine, vol. 364, no. 13, pp. 1207–1217, 2011. View at Publisher · View at Google Scholar · View at Scopus
  29. I. M. Jacobson, G. J. Dore, G. R. Foster 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,” The Lancet, vol. 384, no. 9941, pp. 403–413, 2014. View at Publisher · View at Google Scholar · View at Scopus
  30. M. Manns, P. Marcellin, F. Poordad 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,” The Lancet, vol. 384, no. 9941, pp. 414–426, 2014. View at Publisher · View at Google Scholar · View at Scopus
  31. N. Hayashi, N. Izumi, H. Kumada et al., “Simeprevir with peginterferon/ribavirin for treatment-naïve hepatitis C genotype 1 patients in Japan: CONCERTO-1, a phase III trial,” Journal of Hepatology, vol. 61, no. 2, pp. 219–227, 2014. View at Publisher · View at Google Scholar · View at Scopus
  32. C. Moreno, C. Hezode, P. Marcellin et al., “Efficacy and safety of simeprevir with PegIFN/ribavirin in naïve or experienced patients infected with chronic HCV genotype 4,” Journal of Hepatology, vol. 62, no. 5, pp. 1047–1055, 2015. View at Publisher · View at Google Scholar
  33. N. Hayashi, N. Mobashery, and N. Izumi, “Vaniprevir plus peginterferon alfa-2a and ribavirin in treatment-experienced Japanese patients with hepatitis C virus genotype 1 infection: a randomized phase II study,” Journal of Gastroenterology, vol. 50, no. 2, pp. 238–248, 2015. View at Publisher · View at Google Scholar · View at Scopus
  34. E. Lawitz, A. Mangia, D. Wyles et al., “Sofosbuvir for previously untreated chronic hepatitis C infection,” The New England Journal of Medicine, vol. 368, no. 20, pp. 1878–1887, 2013. View at Publisher · View at Google Scholar · View at Scopus
  35. C. Hézode, G. M. Hirschfield, W. Ghesquiere et al., “Daclatasvir plus peginterferon alfa and ribavirin for treatment-naive chronic hepatitis C genotype 1 or 4 infection: a randomised study,” Gut, vol. 64, pp. 948–956, 2015. View at Publisher · View at Google Scholar · View at Scopus
  36. F. Suzuki, J. Toyota, K. Ikeda et al., “A randomized trial of daclatasvir with peginterferon alfa-2b and ribavirin for HCV genotype 1 infection,” Antiviral Therapy, vol. 19, no. 5, pp. 491–499, 2014. View at Publisher · View at Google Scholar
  37. N. Izumi, O. Yokosuka, N. Kawada et al., “Daclatasvir combined with peginterferon alfa-2a and ribavirin in Japanese patients infected with hepatitis C genotype 1,” Antiviral Therapy, vol. 19, no. 5, pp. 501–510, 2014. View at Publisher · View at Google Scholar
  38. E. Lawitz, F. Poordad, D. M. Brainard et al., “Sofosbuvir with peginterferon-ribavirin for 12 weeks in previously treated patients with hepatitis C genotype 2 or 3 and cirrhosis,” Hepatology, vol. 61, no. 3, pp. 769–775, 2015. View at Publisher · View at Google Scholar
  39. E. J. Gane, C. A. Stedman, R. H. Hyland et al., “Nucleotide polymerase inhibitor sofosbuvir plus ribavirin for hepatitis C,” The New England Journal of Medicine, vol. 368, no. 1, pp. 34–44, 2013. View at Publisher · View at Google Scholar · View at Scopus
  40. E. Lawitz, M. S. Sulkowski, R. Ghalib 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-naïve patients: the COSMOS randomised study,” The Lancet, vol. 384, no. 9956, pp. 1756–1765, 2014. View at Publisher · View at Google Scholar · View at Scopus
  41. M. S. Sulkowski, D. F. Gardiner, M. Rodriguez-Torres et al., “Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection,” The New England Journal of Medicine, vol. 370, no. 3, pp. 211–221, 2014. View at Publisher · View at Google Scholar
  42. N. Afdhal, S. Zeuzem, P. Kwo et al., “Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection,” The New England Journal of Medicine, vol. 370, no. 20, pp. 1889–1898, 2014. View at Publisher · View at Google Scholar · View at Scopus
  43. K. V. Kowdley, S. C. Gordon, K. R. Reddy et al., “Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis,” The New England Journal of Medicine, vol. 370, no. 20, pp. 1879–1888, 2014. View at Publisher · View at Google Scholar · View at Scopus
  44. N. Afdhal, K. R. Reddy, D. R. Nelson et al., “Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection,” The New England Journal of Medicine, vol. 370, no. 16, pp. 1483–1493, 2014. View at Publisher · View at Google Scholar · View at Scopus
  45. M. Mizokami, O. Yokosuka, T. Takehara 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,” The Lancet Infectious Diseases, vol. 6, pp. 645–653, 2015. View at Google Scholar
  46. M. Bourlière, J. Bronowicki, V. de Ledinghen 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),” The Lancet Infectious Diseases, vol. 15, no. 4, pp. 397–404, 2015. View at Publisher · View at Google Scholar
  47. A. Kohli, A. Osinusi, Z. Sims et al., “Virological response after 6 week triple-drug regimens for hepatitis C: a proof-of-concept phase 2A cohort study,” The Lancet, vol. 385, pp. 1107–1113, 2015. View at Publisher · View at Google Scholar · View at Scopus
  48. A. Kohli, R. Kapoor, Z. Sims et al., “Ledipasvir and sofosbuvir for hepatitis C genotype 4: a proof-of-concept, single center, open-label phase 2a cohort study,” The Lancet Infectious Diseases, vol. 15, no. 9, pp. 1049–1054, 2015. View at Publisher · View at Google Scholar
  49. J. J. Feld, I. M. Jacobson, C. Hézode et al., “Sofosbuvir and velpatasvir for HCV genotype 1, 2, 4, 5, and 6 infection,” The New England Journal of Medicine, vol. 373, no. 27, pp. 2599–2607, 2015. View at Publisher · View at Google Scholar
  50. A. S. Lok, D. F. Gardiner, E. Lawitz et al., “Preliminary study of two antiviral agents for hepatitis C genotype 1,” The New England Journal of Medicine, vol. 366, no. 3, pp. 216–224, 2012. View at Publisher · View at Google Scholar · View at Scopus
  51. H. Kumada, Y. Suzuki, K. Ikeda et al., “Daclatasvir plus asunaprevir for chronic HCV genotype 1b infection,” Hepatology, vol. 59, no. 6, pp. 2083–2091, 2014. View at Publisher · View at Google Scholar · View at Scopus
  52. M. Manns, S. Pol, I. M. Jacobson et al., “All-oral daclatasvir plus asunaprevir for hepatitis C virus genotype 1b: a multinational, phase 3, multicohort study,” The Lancet, vol. 384, no. 9954, pp. 1597–1605, 2014. View at Publisher · View at Google Scholar · View at Scopus
  53. F. Poordad, W. Sievert, L. Mollison et al., “Fixed-dose combination therapy with daclatasvir, asunaprevir, and beclabuvir for noncirrhotic patients with HCV genotype 1 infection,” The Journal of the American Medical Association, vol. 313, no. 17, pp. 1728–1735, 2015. View at Publisher · View at Google Scholar
  54. J. J. Feld, K. V. Kowdley, E. Coakley et al., “Treatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin,” The New England Journal of Medicine, vol. 370, no. 17, pp. 1594–1603, 2014. View at Publisher · View at Google Scholar · View at Scopus
  55. P. Ferenci, D. Bernstein, J. Lalezari et al., “ABT-450/r-ombitasvir and dasabuvir with or without ribavirin for HCV,” The New England Journal of Medicine, vol. 370, no. 21, pp. 1983–1992, 2014. View at Publisher · View at Google Scholar · View at Scopus
  56. F. Poordad, C. Hezode, R. Trinh et al., “ABT-450/r-ombitasvir and dasabuvir with ribavirin for hepatitis C with cirrhosis,” The New England Journal of Medicine, vol. 370, no. 21, pp. 1973–1982, 2014. View at Publisher · View at Google Scholar · View at Scopus
  57. C. Hézode, T. Asselah, K. R. Reddy 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,” The Lancet, vol. 385, no. 9986, pp. 2502–2509, 2015. View at Publisher · View at Google Scholar
  58. K. Chayama, K. Notsumata, M. Kurosaki et al., “Randomized trial of interferon- and ribavirin-free ombitasvir/paritaprevir/ritonavir in treatment-experienced hepatitis C virus-infected patients,” Hepatology, vol. 61, no. 5, pp. 1523–1532, 2015. View at Publisher · View at Google Scholar
  59. S. Zeuzem, R. Ghalib, K. R. Reddy et al., “Grazoprevir-elbasvir combination therapy for treatment-naive cirrhotic and noncirrhotic patients with chronic HCV genotype 1, 4, or 6 infection: a randomized trial,” Annals of Internal Medicine, vol. 163, no. 1, pp. 1–13, 2015. View at Google Scholar
  60. I. M. Jacobson, S. C. Gordon, K. V. Kowdley et al., “Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options,” The New England Journal of Medicine, vol. 368, no. 20, pp. 1867–1877, 2013. View at Publisher · View at Google Scholar · View at Scopus
  61. S. Zeuzem, G. M. Dusheiko, R. Salupere et al., “Sofosbuvir and Ribavirin in HCV genotypes 2 and 3,” The New England Journal of Medicine, vol. 370, no. 21, pp. 1993–2001, 2014. View at Publisher · View at Google Scholar · View at Scopus
  62. M. Omata, S. Nishiguchi, Y. Ueno et al., “Sofosbuvir plus ribavirin in Japanese patients with chronic genotype 2 HCV infection: an open-label, phase 3 trial,” Journal of Viral Hepatitis, vol. 21, no. 11, pp. 762–768, 2014. View at Publisher · View at Google Scholar · View at Scopus
  63. D. R. Nelson, J. N. Cooper, J. P. Lalezari 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, vol. 61, no. 4, pp. 1127–1135, 2015. View at Publisher · View at Google Scholar
  64. E. J. Gane, R. H. Hyland, D. An et al., “High efficacy of LDV/SOF regimens for 12 weeks for patients with HCV genotype 3 or 6 infection,” Hepatology, vol. 60, p. 1274A, 2014. View at Google Scholar
  65. J. C. Sullivan, S. De Meyer, D. J. Bartels et al., “Evolution of treatment-emergent resistant variants in telaprevir phase 3 clinical trials,” Clinical Infectious Diseases, vol. 57, no. 2, pp. 221–229, 2013. View at Publisher · View at Google Scholar · View at Scopus
  66. O. Lenz, T. Verbinnen, B. Fevery et al., “Virology analyses of HCV isolates from genotype 1-infected patients treated with simeprevir plus peginterferon/ribavirin in Phase IIb/III studies,” Journal of Hepatology, vol. 62, no. 5, pp. 1008–1014, 2015. View at Publisher · View at Google Scholar
  67. Y. Karino, J. Toyota, K. Ikeda et al., “Characterization of virologic escape in hepatitis C virus genotype 1b patients treated with the direct-acting antivirals daclatasvir and asunaprevir,” Journal of Hepatology, vol. 58, no. 4, pp. 646–654, 2013. View at Publisher · View at Google Scholar · View at Scopus
  68. F. Mcphee, D. Hernandez, F. Yu et al., “Resistance analysis of hepatitis C virus genotype 1 prior treatment null responders receiving daclatasvir and asunaprevir,” Hepatology, vol. 58, no. 3, pp. 902–911, 2013. View at Publisher · View at Google Scholar · View at Scopus
  69. J. Friborg, N. Zhou, Z. Han et al., “In vitro assessment of re-treatment options for patients with hepatitis C Virus genotype 1b infection resistant to daclatasvir plus asunaprevir,” Infectious Diseases and Therapy, vol. 4, no. 1, pp. 137–144, 2015. View at Publisher · View at Google Scholar
  70. J. H. Sun, D. R. O’Boyle II, R. A. Fridell et al., “Resensitizing daclatasvir-resistant hepatitis C variants by allosteric modulation of NS5A,” Nature, vol. 527, no. 7577, pp. 245–248, 2015. View at Publisher · View at Google Scholar
  71. X. Forns, S. C. Gordon, E. Zuckerman et al., “Grazoprevir and elbasvir plus ribavirin for chronic HCV genotype-1 infection after failure of combination therapy containing a direct-acting antiviral agent,” Journal of Hepatology, vol. 63, no. 3, pp. 564–572, 2015. View at Publisher · View at Google Scholar
  72. A. Osinusi, A. Kohli, M. M. Marti et al., “Re-treatment of chronic hepatitis C virus genotype 1 infection after relapse: an open-label pilot study,” Annals of Internal Medicine, vol. 161, no. 9, pp. 634–638, 2014. View at Publisher · View at Google Scholar · View at Scopus
  73. G. V. Papatheodoridis, V. C. Papadimitropoulos, and S. J. Hadziyannis, “Effect of interferon therapy on the development of hepatocellular carcinoma in patients with hepatitis C virus-related cirrhosis: a meta-analysis,” Alimentary Pharmacology and Therapeutics, vol. 15, no. 5, pp. 689–698, 2001. View at Publisher · View at Google Scholar · View at Scopus
  74. S. Bruno, T. Stroffolini, M. Colombo et al., “Sustained virological response to interferon-α is with improved outcome in HCV-related cirrhosis: a retrospective study,” Hepatology, vol. 45, no. 3, pp. 579–587, 2007. View at Publisher · View at Google Scholar · View at Scopus
  75. Y. Imai, S. Tamura, H. Tanaka et al., “Reduced risk of hepatocellular carcinoma after interferon therapy in aged patients with chronic hepatitis C is limited to sustained virological responders,” Journal of Viral Hepatitis, vol. 17, no. 3, pp. 185–191, 2010. View at Publisher · View at Google Scholar · View at Scopus
  76. A. Makiyama, Y. Itoh, A. Kasahara et al., “Characteristics of patients with chronic hepatitis C who develop hepatocellular carcinoma after a sustained response to interferon therapy,” Cancer, vol. 101, no. 7, pp. 1616–1622, 2004. View at Publisher · View at Google Scholar · View at Scopus
  77. S. Kobayashi, T. Takeda, M. Enomoto et al., “Development of hepatocellular carcinoma in patients with chronic hepatitis C who had a sustained virological response to interferon therapy: a multicenter, retrospective cohort study of 1124 patients,” Liver International, vol. 27, no. 2, pp. 186–191, 2007. View at Publisher · View at Google Scholar · View at Scopus
  78. T. Oze, N. Hiramatsu, T. Yakushijin et al., “Post-treatment levels of α-fetoprotein predict incidence of hepatocellular carcinoma after interferon therapy,” Clinical Gastroenterology and Hepatology, vol. 12, no. 7, pp. 1186–1195, 2014. View at Publisher · View at Google Scholar · View at Scopus
  79. Y. Asahina, K. Tsuchiya, N. Tamaki et al., “Effect of aging on risk for hepatocellular carcinoma in chronic hepatitis C virus infection,” Hepatology, vol. 52, no. 2, pp. 518–527, 2010. View at Publisher · View at Google Scholar · View at Scopus
  80. E. G. Meissner, Y. J. Lee, A. Osinusi et al., “Effect of sofosbuvir and ribavirin treatment on peripheral and hepatic lipid metabolism in chronic hepatitis C virus, genotype 1-infected patients,” Hepatology, vol. 61, no. 3, pp. 790–801, 2015. View at Publisher · View at Google Scholar
  81. Z. M. Younossi, M. Stepanova, N. Afdhal 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,” Journal of Hepatology, vol. 63, no. 2, pp. 337–345, 2015. View at Publisher · View at Google Scholar