Table of Contents Author Guidelines Submit a Manuscript
International Journal of Hepatology
Volume 2011, Article ID 314301, 8 pages
http://dx.doi.org/10.4061/2011/314301
Review Article

The Impact of Antiviral Therapy and the Influence of Metabolic Cofactors on the Outcome of Chronic HCV Infection

1Internal Medicine and Hepatology Division, Second University of Naples, Via Del Parco Carelli 36, 80123 Naples, Italy
2Department of Internal Medicine, AO Fatebenefratelli e Oftalmico, Corso di Porta Nuova 23, 20121 Milano, Italy
3Gastroenterology & Hepatology Unit, Di.Bi.M.I.S., University of Palermo, Piazza delle Cliniche, 2, 90127 Palermo, Italy

Received 30 December 2010; Revised 9 August 2011; Accepted 18 August 2011

Academic Editor: Richard Guan

Copyright © 2011 Marcello Persico 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. G. Fattovich, M. Pantalena, I. Zagni, G. Realdi, S. W. Schalm, and E. Christensen, “Effect of hepatitis B and C virus infections on the natural history of compensated cirrhosis: a cohort study of 297 patients,” American Journal of Gastroenterology, vol. 97, no. 11, pp. 2886–2895, 2002. View at Google Scholar · View at Scopus
  2. L. Serfaty, H. Aumaître, O. Chazouillères et al., “Determinants of outcome of compensated hepatitis C virus-related cirrhosis,” Hepatology, vol. 27, no. 5, pp. 1435–1440, 1998. View at Publisher · View at Google Scholar · View at Scopus
  3. K. Q. Hu and M. J. Tong, “The long-term outcomes of patients with compensated hepatitis C virus- related cirrhosis and history of parenteral exposure in the United States,” Hepatology, vol. 29, no. 4, pp. 1311–1316, 1999. View at Google Scholar · View at Scopus
  4. L. Benvegnù, M. Gios, S. Boccato, and A. Alberti, “Natural history of compensated viral cirrhosis: a prospective study on the incidence and hierarchy of major complications,” Gut, vol. 53, no. 5, pp. 744–749, 2004. View at Publisher · View at Google Scholar · View at Scopus
  5. G. Fattovich, G. Giustina, F. Degos et al., “Morbidity and mortality in compensated cirrhosis type C: a retrospective follow-up study of 384 patients,” Gastroenterology, vol. 112, no. 2, pp. 463–472, 1997. View at Publisher · View at Google Scholar · View at Scopus
  6. M. P. Manns, J. G. McHutchison, S. C. Gordon et al., “Peginterferon alfa-2b plus ribavirin compared with interferonalfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial,” The Lancet, vol. 358, no. 9286, pp. 958–965, 2001. View at Publisher · View at Google Scholar · View at Scopus
  7. M. W. Fried, M. L. Shiffman, K. Rajender Reddy et al., “Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection,” The New England Journal of Medicine, vol. 347, no. 13, pp. 975–982, 2002. View at Publisher · View at Google Scholar · View at Scopus
  8. J. G. Mchutchison, S. C. Gordon, E. R. Schiff et al., “Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C,” The New England Journal of Medicine, vol. 339, no. 21, pp. 1485–1492, 1998. View at Publisher · View at Google Scholar
  9. S. J. Hadziyannis, H. Sette Jr., T. R. Morgan et al., “Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose,” Annals of Internal Medicine, vol. 140, no. 5, pp. 346–355, 2004. View at Google Scholar · View at Scopus
  10. S. L. George, B. R. Bacon, E. M. Brunt, K. L. Mihindukulasuriya, J. Hoffman, and A. M. Di Bisceglie, “Clinical, virologic, histologic, and biochemical outcomes after successful HCV therapy: a 5-year follow-up of 150 patients,” Hepatology, vol. 49, no. 3, pp. 729–738, 2009. View at Publisher · View at Google Scholar · View at Scopus
  11. B. J. Veldt, E. J. Heathcote, H. Wedemeyer et al., “Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis,” Annals of Internal Medicine, vol. 147, no. 10, pp. 677–684, 2007. View at Google Scholar · View at Scopus
  12. V. Di Marco, P. L. Almasio, D. Ferraro et al., “Peg-interferon alone or combined with ribavirin in HCV cirrhosis with portal hypertension: a randomized controlled trial,” Journal of Hepatology, vol. 47, no. 4, pp. 484–491, 2007. View at Publisher · View at Google Scholar · View at Scopus
  13. L. Serfaty, A. Poujol-Robert, N. Carbonell, O. Chazouillères, R. E. Poupon, and R. Poupon, “Effect of the interaction between steatosis and alcohol intake on liver fibrosis progression in chronic hepatitis C,” American Journal of Gastroenterology, vol. 97, no. 7, pp. 1807–1812, 2002. View at Publisher · View at Google Scholar · View at Scopus
  14. G. Kuo, Q. L. Choo, H. J. Alter et al., “An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis,” Science, vol. 244, no. 4902, pp. 362–364, 1989. View at Google Scholar · View at Scopus
  15. L. B. Seeff, “Natural history of chronic hepatitis C,” Hepatology, vol. 36, no. 5, pp. S35–S46, 2002. View at Publisher · View at Google Scholar · View at Scopus
  16. M. J. Tong, N. S. El-Farra, A. R. Reikes, and R. L. Co, “Clinical outcomes after transfusion-associated hepatitis C,” The New England Journal of Medicine, vol. 332, no. 22, pp. 1463–1466, 1995. View at Publisher · View at Google Scholar · View at Scopus
  17. A. M. Di Bisceglie, Z. D. Goodman, K. G. Ishak, J. H. Hoofnagle, J. J. Melpolder, and H. J. Alter, “Long-term clinical and histopathological follow-up of chronic posttransfusion hepatitis,” Hepatology, vol. 14, no. 6, pp. 969–974, 1991. View at Publisher · View at Google Scholar · View at Scopus
  18. R. L. Koretz, H. Abbey, E. Coleman, and G. Gitnick, “Non-A, non-B post-transfusion hepatitis: looking back in the second decade,” Annals of Internal Medicine, vol. 119, no. 2, pp. 110–115, 1993. View at Google Scholar · View at Scopus
  19. E. Kenny-Walsh and F. Shanahan, “Clinical outcomes after hepatitis C infection from contaminated anti-D immune globulin,” The New England Journal of Medicine, vol. 340, no. 16, pp. 1228–1233, 1999. View at Publisher · View at Google Scholar
  20. M. Wiese, F. Berr, M. Lafrenz, H. Porst, and U. Oesen, “Low frequency of cirrhosis in a hepatitis C (genotype 1b) single-source outbreak in Germany: a 20-year multicenter study,” Hepatology, vol. 32, no. 1, pp. 91–96, 2000. View at Google Scholar · View at Scopus
  21. M. Vogt, T. Lang, G. Frösner et al., “Prevalence and clinical outcome of hepatitis C infection in children who underwent cardiac surgery before the implementation of blood-donor screening,” The New England Journal of Medicine, vol. 341, no. 12, pp. 866–870, 1999. View at Publisher · View at Google Scholar · View at Scopus
  22. L. B. Seeff, F. B. Hollinger, H. J. Alter et al., “Long-term mortality and morbidity of transfusion-associated non-A, non-B, and type C hepatitis: a National Heart, Lung, and Blood Institute Collaborative Study,” Hepatology, vol. 33, no. 2, pp. 455–463, 2001. View at Publisher · View at Google Scholar · View at Scopus
  23. A. J. Rodger, S. Roberts, A. Lanigan, S. Bowden, T. Brown, and N. Crofts, “Assessment of long-term outcomes of community-acquired hepatitis C infection in a cohort with sera stored from 1971 to 1975,” Hepatology, vol. 32, no. 3, pp. 582–587, 2000. View at Google Scholar · View at Scopus
  24. L. B. Seeff, R. N. Miller, C. S. Rabkin et al., “45-Year follow-up of hepatitis C virus infection in healthy young adults,” Annals of Internal Medicine, vol. 132, no. 2, pp. 105–111, 2000. View at Google Scholar · View at Scopus
  25. M. Persico, E. Persico, R. Suozzo et al., “Natural history of hepatitis C virus carriers with persistently normal aminotransferase levels,” Gastroenterology, vol. 118, no. 4, pp. 760–764, 2000. View at Google Scholar · View at Scopus
  26. S. Rossi, F. De Filippi, S. Saibeni et al., “A 15-Yr prospective histological follow-up study in patients with persistently normal aminotransferase levels (PNAL) carrying HCV infection,” American Journal of Gastroenterology, vol. 102, no. 11, pp. 2604–2606, 2007. View at Publisher · View at Google Scholar · View at Scopus
  27. M. G. Rumi, F. De Filippi, M. F. Donato, E. Del Ninno, and M. Colombo, “Progressive hepatic fibrosis in healthy carriers of hepatitis C virus with a transaminase breakthrough,” Journal of Viral Hepatitis, vol. 9, no. 1, pp. 71–74, 2002. View at Publisher · View at Google Scholar · View at Scopus
  28. S. Raimondi, S. Bruno, M. U. Mondelli, and P. Maisonneuve, “Hepatitis C virus genotype 1b as a risk factor for hepatocellular carcinoma development: a meta-analysis,” Journal of Hepatology, vol. 50, no. 6, pp. 1142–1154, 2009. View at Publisher · View at Google Scholar · View at Scopus
  29. S. Bruno, M. Zuin, A. Crosignani et al., “Predicting mortality risk in patients with compensated HCV-induced cirrhosis: a long-term prospective study,” American Journal of Gastroenterology, vol. 104, no. 5, pp. 1147–1157, 2009. View at Publisher · View at Google Scholar · View at Scopus
  30. S. Bruno, A. Crosignani, C. Facciotto 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, vol. 51, no. 6, pp. 2069–2076, 2010. View at Publisher · View at Google Scholar · View at Scopus
  31. M. Kobayashi, E. Tanaka, T. Sodeyama, A. Urushihara, A. Matsumoto, and K. Kiyosawa, “The natural course of chronic hepatitis C: a comparison between patients with genotype 1 and 2 hepatitis C viruses,” Hepatology, vol. 34, pp. 764–767, 2001. View at Google Scholar
  32. L. Roffi, A. Ricci, C. Ogliari et al., “HCV genotypes in Northern Italy: a survey of 1368 histologically proven chronic hepatitis C patients,” Journal of Hepatology, vol. 29, no. 5, pp. 701–706, 1998. View at Publisher · View at Google Scholar · View at Scopus
  33. S. Zeuzem, A. Franke, J. H. Lee, G. Herrmann, B. Rüster, and W. K. Roth, “Phylogenetic analysis of hepatitis C virus isolates and their correlation to viremia, liver function tests, and histology,” Hepatology, vol. 24, no. 5, pp. 1003–1009, 1996. View at Publisher · View at Google Scholar · View at Scopus
  34. P. Farci, A. Shimoda, A. Coiana et al., “The outcome of acute hepatitis C predicted by the evolution of the viral quasispecies,” Science, vol. 288, no. 5464, pp. 339–344, 2000. View at Publisher · View at Google Scholar · View at Scopus
  35. B. Soto, A. Sánchez-Quijano, L. Rodrigo et al., “Human immunodeficiency virus infection modifies the natural history of chronic parenterally-acquired hepatitis C with an unusually rapid progression to cirrhosis,” Journal of Hepatology, vol. 26, no. 1, pp. 1–5, 1997. View at Publisher · View at Google Scholar · View at Scopus
  36. P. Pontisso, M. Gerotto, L. Benvegnu, L. Chemello, and A. Alberti, “Coinfection by hepatitis B virus and hepatitis C virus,” Antiviral Therapy, vol. 3, no. 3, pp. 137–142, 1998. View at Google Scholar · View at Scopus
  37. R. K. Sterling and M. S. Sulkowski, “Hepatitis C virus in the setting of HIV or hepatitis B virus coinfection,” Seminars in Liver Disease, vol. 24, no. 2, supplement, pp. 61–68, 2004. View at Publisher · View at Google Scholar · View at Scopus
  38. J. R. Pallás, C. Fariñas-Álvarez, D. Prieto, and M. Delgado-Rodríguez, “Coinfections by HIV, hepatitis B and hepatitis C in imprisoned injecting drug users,” European Journal of Epidemiology, vol. 15, no. 8, pp. 699–704, 1999. View at Publisher · View at Google Scholar
  39. G. A. Reddy, K. V. Dakshinamurthy, P. Neelaprasad, T. Gangadhar, and V. Lakshmi, “Prevalence of HBV and HCV dual infection in patients on haemodialysis,” Indian Journal of Medical Microbiology, vol. 23, no. 1, pp. 41–43, 2005. View at Google Scholar · View at Scopus
  40. A. Aroldi, P. Lampertico, G. Montagnino et al., “Natural history of hepatitis B and C in renal allograft recipients,” Transplantation, vol. 79, no. 9, pp. 1132–1136, 2005. View at Publisher · View at Google Scholar · View at Scopus
  41. A. Kalinowska-Nowak, M. Bociaga-Jasik, A. Garlicki, and P. Skwara, “Prevalence of hepatotropic viruses HBV and HCV in HIV-infected patients from Southern region of Poland,” Acta Virologica, vol. 44, pp. 23–28, 2000. View at Google Scholar
  42. J. Zhou, G. J. Dore, F. Zhang, P. L. Lim, and Y. M. A. Chen, “Hepatitis B and C virus coinfection in the TREAT Asia HIV Observational Database,” Journal of Gastroenterology and Hepatology, vol. 22, no. 9, pp. 1510–1518, 2007. View at Publisher · View at Google Scholar · View at Scopus
  43. E. Angelucci, P. Muretto, A. Nicolucci et al., “Effects of iron overload and hepatitis C virus positivity in determining progression of liver fibrosis in thalassemia following bone marrow transplantation,” Blood, vol. 100, no. 1, pp. 17–21, 2002. View at Publisher · View at Google Scholar · View at Scopus
  44. V. Di Marco, M. Capra, F. Gagliardotto et al., “Liver disease in chelated transfusion-dependent thalassemics: the role of iron overload and chronic hepatitis C,” Haematologica, vol. 93, no. 8, pp. 1243–1246, 2008. View at Publisher · View at Google Scholar · View at Scopus
  45. J. P. Zarski, B. Bohn, A. Bastie et al., “Characteristics of patients with dual infection by hepatitis B and C viruses,” Journal of Hepatology, vol. 28, no. 1, pp. 27–33, 1998. View at Publisher · View at Google Scholar · View at Scopus
  46. J. Crespo, J. L. Lozano, F. De la Cruz et al., “Prevalence and significance of hepatitis C viremia in chronic active hepatitis B,” American Journal of Gastroenterology, vol. 89, no. 8, pp. 1147–1151, 1994. View at Google Scholar · View at Scopus
  47. A. E. Mohamed, M. Ali Al Karawi, and G. A. Mesa, “Dual infection with hepatitis C and B viruses: clinical and histological study in Saudi patients,” Hepato-Gastroenterology, vol. 44, no. 17, pp. 1404–1406, 1997. View at Google Scholar · View at Scopus
  48. J. P. Zarski, B. Bohn, A. Bastie et al., “Characteristics of patients with dual infection by hepatitis B and C viruses,” Journal of Hepatology, vol. 28, no. 1, pp. 27–33, 1998. View at Publisher · View at Google Scholar · View at Scopus
  49. G. Fattovich, A. Tagger, L. Brollo et al., “Hepatitis C virus infection in chronic hepatitis B virus carriers,” Journal of Infectious Diseases, vol. 163, no. 2, pp. 400–402, 1991. View at Google Scholar · View at Scopus
  50. T. L. Fong, A. M. Di Bisceglie, J. G. Waggoner, S. M. Banks, and J. H. Hoofnagle, “The significance of antibody to hepatitis C virus in patients with chronic hepatitis B,” Hepatology, vol. 14, no. 1, pp. 64–67, 1991. View at Google Scholar · View at Scopus
  51. H. E. Kuper, M. Tzonou A, and G. A. Kaklamani E, “Hepatitis B and C viruses in the etiology of hepatocellular carcinoma; a study in Greece using third-generation assays,” Cancer Causes Control, vol. 2, pp. 171–175, 2000. View at Google Scholar · View at Scopus
  52. E. Kaklamani, D. Trichopoulos, A. Tzonou et al., “Hepatitis B and C viruses and their interaction in the origin of hepatocellular carcinoma,” Journal of the American Medical Association, vol. 265, no. 15, pp. 1974–1976, 1991. View at Publisher · View at Google Scholar · View at Scopus
  53. M. C. Kew, M. C. Yu, M. A. Kedda, A. Coppin, A. Sarkin, and J. Hodkinson, “The relative roles of hepatitis B and C viruses in the etiology of hepatocellular carcinoma in southern African blacks,” Gastroenterology, vol. 112, no. 1, pp. 184–187, 1997. View at Google Scholar · View at Scopus
  54. G. D. Kirk, O. A. Lesi, M. Mendy et al., “The Gambia Liver Cancer Study: infection with hepatitis B and C and the risk of hepatocellular carcinoma in West Africa,” Hepatology, vol. 39, no. 1, pp. 211–219, 2004. View at Publisher · View at Google Scholar · View at Scopus
  55. Panel on Antiretroviral Guidelines for Adults and Adolescents, Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services, pp.1–166, January 2011.
  56. T. W. Lapinski, A. Parfieniuk, M. Rogalska-Plonska, J. Czajkowska, and R. Flisiak, “Prevalence of cryoglobulinaemia in hepatitis C virus- and hepatitis C virus/human immunodeficiency virus-infected individuals: implications for renal function,” Liver International, vol. 29, no. 8, pp. 1158–1161, 2009. View at Publisher · View at Google Scholar · View at Scopus
  57. J. S. Reingold, C. Wanke, D. P. Kotler et al., “Association of HIV infection and HIV/HCV coinfection with C-reactive protein levels: the fat redistribution and metabolic change in HIV infection (FRAM) study,” Journal of Acquired Immune Deficiency Syndromes, vol. 48, no. 2, pp. 142–148, 2008. View at Publisher · View at Google Scholar · View at Scopus
  58. C. M. Wyatt, C. Malvestutto, S. G. Coca, P. E. Klotman, and C. R. Parikh, “The impact of hepatitis C virus coinfection on HIV-related kidney disease: a systematic review and meta-analysis,” AIDS, vol. 22, no. 14, pp. 1799–1807, 2008. View at Publisher · View at Google Scholar · View at Scopus
  59. M. J. Fischer, C. M. Wyatt, K. Gordon et al., “Hepatitis C and the risk of kidney disease and mortality in veterans with HIV,” Journal of Acquired Immune Deficiency Syndromes, vol. 53, no. 2, pp. 222–226, 2010. View at Publisher · View at Google Scholar · View at Scopus
  60. R. Bedimo, A. O. Westfall, M. Mugavero, H. Drechsler, N. Khanna, and M. Saag, “Hepatitis C virus coinfection and the risk of cardiovascular disease among HIV-infected patients,” HIV Medicine, vol. 11, no. 7, pp. 462–468, 2010. View at Publisher · View at Google Scholar · View at Scopus
  61. I. F. De Castro, D. Micheloud, J. Berenguer et al., “Hepatitis C virus infection is associated with endothelial dysfunction in HIV/hepatitis C virus coinfected patients,” AIDS, vol. 24, no. 13, pp. 2059–2067, 2010. View at Publisher · View at Google Scholar · View at Scopus
  62. S. Letendre, A. D. Paulino, E. Rockenstein et al., “Pathogenesis of hepatitis C virus coinfection in the brains of patients infected with HIV,” Journal of Infectious Diseases, vol. 196, no. 3, pp. 361–370, 2007. View at Publisher · View at Google Scholar · View at Scopus
  63. P. Vivithanaporn, F. Maingat, L. T. Lin et al., “Hepatitis C virus core protein induces neuroimmune activation and potentiates human immunodeficiency virus-1 neurotoxicity,” PLoS ONE, vol. 5, no. 9, Article ID e12856, pp. 1–14, 2010. View at Publisher · View at Google Scholar · View at Scopus
  64. H. A. Aronow, A. J. Weston, B. B. Pezeshki, and T. S. Lazarus, “Effects of coinfection with HIV and hepatitis C virus on the nervous system,” AIDS Reader, vol. 18, no. 1, pp. 43–48, 2008. View at Google Scholar · View at Scopus
  65. C. H. Hinkin, S. A. Castellon, A. J. Levine, T. R. Barclay, and E. J. Singer, “Neurocognition in individuals co-infected with HIV and hepatitis C,” Journal of Addictive Diseases, vol. 27, no. 2, pp. 11–17, 2008. View at Publisher · View at Google Scholar · View at Scopus
  66. E. Minola, D. Prati, F. Suter et al., “Age at infection affects the long-term outcome of transfusion-associated chronic hepatitis C,” Blood, vol. 99, no. 12, pp. 4588–4591, 2002. View at Publisher · View at Google Scholar · View at Scopus
  67. C. Cammà, S. Bruno, V. Di Marco et al., “Insulin resistance is associated with steatosis in nondiabetic patients with genotype 1 chronic hepatitis C,” Hepatology, vol. 43, no. 1, pp. 64–71, 2006. View at Publisher · View at Google Scholar · View at Scopus
  68. V. Ortiz, M. Berenguer, J. M. Rayón, D. Carrasco, and J. Berenguer, “Contribution of obesity to hepatitis C-related fibrosis progression,” American Journal of Gastroenterology, vol. 97, no. 9, pp. 2408–2414, 2002. View at Publisher · View at Google Scholar · View at Scopus
  69. A. Monto, “Hepatitis C and steatosis,” Seminars in Gastrointestinal Disease, vol. 13, no. 1, pp. 40–46, 2002. View at Google Scholar · View at Scopus
  70. R. D'Souza, C. A. Sabin, and G. R. Foster, “Insulin resistance plays a significant role in liver fibrosis in chronic hepatitis C and in the response to antiviral therapy,” American Journal of Gastroenterology, vol. 100, no. 7, pp. 1509–1515, 2005. View at Publisher · View at Google Scholar · View at Scopus
  71. M. Persico, M. Capasso, E. Persico et al., “Suppressor of cytokine signaling 3 (SOCS3) expression and hepatitis C virus-related chronic hepatitis: insulin resistance and response to antiviral therapy,” Hepatology, vol. 46, no. 4, pp. 1009–1015, 2007. View at Publisher · View at Google Scholar · View at Scopus
  72. M. Persico, R. Russo, E. Persico et al., “SOCS3 and IRS-1 gene expression differs between genotype 1 and genotype 2 hepatitis C virus-infected HepG2 cells,” Clinical Chemistry and Laboratory Medicine, vol. 47, no. 10, pp. 1217–1225, 2009. View at Publisher · View at Google Scholar · View at Scopus
  73. J. E. Everhart, A. S. Lok, H. Y. Kim et al., “Weight-related effects on disease progression in the hepatitis C antiviral long-term treatment against cirrhosis trial,” Gastroenterology, vol. 137, no. 2, pp. 549–557, 2009. View at Publisher · View at Google Scholar · View at Scopus
  74. H. L. Bonkovsky, B. F. Banner, and A. L. Rothman, “Iron and chronic viral hepatitis,” Hepatology, vol. 25, no. 3, pp. 759–768, 1997. View at Publisher · View at Google Scholar · View at Scopus
  75. A. M. Di Bisceglie, H. L. Bonkovsky, S. Chopra et al., “Iron reduction as an adjuvant to interferon therapy in patients with chronic hepatitis C who have previously not responded to interferon: a multicenter, prospective, randomized, controlled trial,” Hepatology, vol. 32, no. 1, pp. 135–138, 2000. View at Google Scholar · View at Scopus
  76. D. Thorburn, G. Curry, R. Spooner et al., “The role of iron and haemochromatosis gene mutations in the progression of liver disease in chronic hepatitis C,” Gut, vol. 50, no. 2, pp. 248–252, 2002. View at Publisher · View at Google Scholar · View at Scopus
  77. S. Matsuoka, K. Nirei, A. Tamura et al., “Influence of occult hepatitis B virus coinfection on the incidence of fibrosis and hepatocellular carcinoma in chronic hepatitis C,” Intervirology, vol. 51, no. 5, pp. 352–361, 2009. View at Publisher · View at Google Scholar · View at Scopus
  78. H. L. Bonkovsky, D. Naishadham, R. W. Lambrecht et al., “Roles of iron and HFE mutations on severity and response to therapy during retreatment of advanced chronic hepatitis C,” Gastroenterology, vol. 131, no. 5, pp. 1440–1451, 2006. View at Publisher · View at Google Scholar
  79. R. W. Lambrecht, R. K. Sterling, D. Naishadham et al., “Iron levels in hepatocytes and portal tract cells predict progression and outcomes of patients with advanced chronic hepatitis C,” Gastroenterology, vol. 140, no. 5, pp. 1490–1500.e3, 2011. View at Publisher · View at Google Scholar
  80. G. Corrao and S. Arico, “Independent and combined action of hepatitis C virus infection and alcohol consumption on the risk of symptomatic liver cirrhosis,” Hepatology, vol. 27, no. 4, pp. 914–919, 1998. View at Publisher · View at Google Scholar · View at Scopus
  81. G. Ostapowicz, K. J. R. Watson, S. A. Locarnini, and P. V. Desmond, “Role of alcohol in the progression of liver disease caused by hepatitis C virus infection,” Hepatology, vol. 27, no. 6, pp. 1730–1735, 1998. View at Publisher · View at Google Scholar · View at Scopus
  82. F. Pessione, F. Degos, P. Marcellin et al., “Effect of alcohol consumption on serum hepatitis C virus RNA and histological lesions in chronic hepatitis C,” Hepatology, vol. 27, no. 6, pp. 1717–1722, 1998. View at Publisher · View at Google Scholar · View at Scopus
  83. T. E. Wiley, M. Mccarthy, L. Breidi, M. Mccarthy, and T. J. Layden, “Impact of alcohol on the histological and clinical progression of hepatitis C infection,” Hepatology, vol. 28, no. 3, pp. 805–809, 1998. View at Google Scholar · View at Scopus
  84. G. Fattovich, T. Stroffolini, I. Zagni, and F. Donato, “Hepatocellular carcinoma in cirrhosis: incidence and risk factors,” Gastroenterology, vol. 127, supplement, pp. S35–S50, 2004. View at Publisher · View at Google Scholar · View at Scopus
  85. K. Q. Hu and M. J. Tong, “The long-term outcomes of patients with compensated hepatitis C virus- related cirrhosis and history of parenteral exposure in the United States,” Hepatology, vol. 29, no. 4, pp. 1311–1316, 1999. View at Google Scholar · View at Scopus
  86. L. Benvegnù, M. Gios, S. Boccato, and A. Alberti, “Natural history of compensated viral cirrhosis: a prospective study on the incidence and hierarchy of major complications,” Gut, vol. 53, no. 5, pp. 744–749, 2004. View at Publisher · View at Google Scholar · View at Scopus
  87. A. Sangiovanni, G. M. Prati, P. Fasani et al., “The natural history of compensated cirrhosis due to hepatitis C virus: a 17-year cohort study of 214 patients,” Hepatology, vol. 43, no. 6, pp. 1303–1310, 2006. View at Publisher · View at Google Scholar · View at Scopus
  88. F. Degos, C. Christidis, N. Ganne-Carrie et al., “Hepatitis C virus related cirrhosis: time to occurrence of hepatocellular carcinoma and death,” Gut, vol. 47, no. 1, pp. 131–136, 2000. View at Publisher · View at Google Scholar · View at Scopus
  89. C. Ripoll, R. J. Groszmann, G. Garcia-Tsao et al., “Hepatic venous pressure gradient predicts development of hepatocellular carcinoma independently of severity of cirrhosis,” Journal of Hepatology, vol. 50, no. 5, pp. 923–928, 2009. View at Publisher · View at Google Scholar · View at Scopus
  90. K. W. Kim, S. K. Bae, O. H. Lee, M. H. Bae, M. J. Lee, and B. C. Park, “Insulin-like growth factor II induced by hypoxia may contribute to angiogenesis of human hepatocellular carcinoma,” Cancer Research, vol. 58, no. 2, pp. 348–351, 1998. View at Google Scholar · View at Scopus
  91. S. Bruno, E. Silini, A. Crosignani et al., “Hepatitis C virus genotypes and risk of hepatocellular carcinoma in cirrhosis: a prospective study,” Hepatology, vol. 25, no. 3, pp. 754–758, 1997. View at Publisher · View at Google Scholar · View at Scopus
  92. S. Bruno, A. Crosignani, P. Maisonneuve, S. Rossi, E. Silini, and M. U. Mondelli, “Hepatitis C virus genotype 1b as a major risk factor associated with hepatocellular carcinoma in patients with cirrhosis: a seventeen-year prospective cohort study,” Hepatology, vol. 46, no. 5, pp. 1350–1356, 2007. View at Publisher · View at Google Scholar · View at Scopus
  93. Y. Nishise, T. Saito, K. Sugahara et al., “Risk of hepatocellular carcinoma and secondary structure of hepatitis C virus (HCV) NS3 protein amino-terminus, in patients infected with HCV subtype 1b,” Journal of Infectious Diseases, vol. 196, no. 7, pp. 1006–1009, 2007. View at Publisher · View at Google Scholar · View at Scopus
  94. L. Benvegnù, M. Gios, S. Boccato, and A. Alberti, “Natural history of compensated viral cirrhosis: a prospective study on the incidence and hierarchy of major complications,” Gut, vol. 53, no. 5, pp. 744–749, 2004. View at Publisher · View at Google Scholar · View at Scopus
  95. G. D'Amico, G. Garcia-Tsao, and L. Pagliaro, “Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies,” Journal of Hepatology, vol. 44, no. 1, pp. 217–231, 2006. View at Publisher · View at Google Scholar · View at Scopus
  96. F. Durand and D. Valla, “Assessment of prognosis of cirrhosis,” Seminars in Liver Disease, vol. 28, no. 1, pp. 110–122, 2008. View at Publisher · View at Google Scholar · View at Scopus
  97. 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
  98. B. J. Veldt, E. J. Heathcote, H. Wedemeyer et al., “Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis,” Annals of Internal Medicine, vol. 147, no. 10, pp. 677–684, 2007. View at Google Scholar · View at Scopus
  99. T. Asselah and P. Marcellin, “New direct-acting antivirals' combination for the treatment of chronic hepatitis C,” Liver International, vol. 31, no. 1, supplement, pp. 68–77, 2011. View at Publisher · View at Google Scholar · View at Scopus
  100. Y. Shiratori, F. Imazeki, M. Moriyama et al., “Histologic improvement of fibrosis in patients with hepatitis C who have sustained response to interferon therapy,” Annals of Internal Medicine, vol. 132, no. 7, pp. 517–524, 2000. View at Google Scholar · View at Scopus
  101. C. Cammà, D. Di Bona, F. Schepis et al., “Effect of peginterferon alfa-2a on liver histology in chronic hepatitis C: a meta-analysis of individual patient data,” Hepatology, vol. 39, no. 2, pp. 333–342, 2004. View at Publisher · View at Google Scholar · View at Scopus
  102. T. Poynard, J. McHutchison, M. Manns et al., “Impact of pegylated interferon alfa-2b and ribavirin on liver fibrosis in patients with chronic hepatitis C,” Gastroenterology, vol. 122, no. 5, pp. 1303–1313, 2002. View at Google Scholar · View at Scopus
  103. P. Marcellin, N. Boyer, C. Degott et al., “Long-term histologic and viral changes in patients with chronic hepatitis C who responded to alpha interferon,” Liver, vol. 14, no. 6, pp. 302–307, 1994. View at Google Scholar · View at Scopus
  104. S. L. George, B. R. Bacon, E. M. Brunt, K. L. Mihindukulasuriya, J. Hoffman, and A. M. Di Bisceglie, “Clinical, virologic, histologic, and biochemical outcomes after successful HCV therapy: a 5-year follow-up of 150 patients,” Hepatology, vol. 49, no. 3, pp. 729–738, 2009. View at Publisher · View at Google Scholar · View at Scopus
  105. P. Marcellin, N. Boyer, A. Gervais et al., “Long-term histologic improvement and loss of detectable intrahepatic HCV RNA in patients with chronic hepatitis C and sustained response to interferon-α therapy,” Annals of Internal Medicine, vol. 127, no. 10, pp. 875–881, 1997. View at Google Scholar · View at Scopus
  106. M. Sata, T. Ide, and F. Akiyoshi, “Effects of interferon alpha 2a on incidence of hepatocellular carcinoma in chronic active hepatitis without cirrhosis,” Kurume Medical Journal, vol. 44, pp. 171–177, 1997. View at Google Scholar
  107. D. T. Y. Lau, D. E. Kleiner, M. G. Ghany, Y. Park, P. Schmio, and J. H. Hoofnagle, “10-year follow-up after interferon-α therapy for chronic hepatitis C,” Hepatology, vol. 28, no. 4 I, pp. 1121–1127, 1998. View at Publisher · View at Google Scholar · View at Scopus
  108. C. Cammà, V. Di Marco, O. Lo Iacono et al., “Long-term course of interferon-treated chronic hepatitis C,” Journal of Hepatology, vol. 28, no. 4, pp. 531–537, 1998. View at Publisher · View at Google Scholar · View at Scopus
  109. A. Ajello, M. A. Freni, A. Spadaro et al., “Ten year follow-up of patients with chronic hepatitis C treated with interferon,” Hepato-Gastroenterology, vol. 46, no. 28, pp. 2447–2450, 1999. View at Google Scholar · View at Scopus
  110. F. Morisco, R. Marmo, P. Iasevoli et al., “Clinical outcome of chronic hepatitis C in patients treated with interferon: comparison between responders and non-responders,” Italian Journal of Gastroenterology and Hepatology, vol. 31, no. 6, pp. 454–458, 1999. View at Google Scholar
  111. A. Gallego, X. Torras, F. J. Sancho-Poch, and J. Enriquez, “Long term follow-up of patient with chronic hepatitis C after IFN therapy,” Journal of Hepatology, vol. 34, supplement 1, p. 234, 2001. View at Google Scholar
  112. E. Giannini, A. Fasoli, F. Botta et al., “Long-term follow up of chronic hepatitis C patients after α-interferon treatment: a functional study,” Journal of Gastroenterology and Hepatology, vol. 16, no. 4, pp. 399–405, 2001. View at Publisher · View at Google Scholar
  113. M. Shindo, K. Hamada, Y. Oda, and T. Okuno, “Long-term follow-up study of sustained biochemical responders with interferon therapy,” Hepatology, vol. 33, no. 5, pp. 1299–1302, 2001. View at Publisher · View at Google Scholar · View at Scopus
  114. M. Swain, M. Y. Lai, M. L. Shiffman et al., “Durability of sustained virological response (SVR) after treatment with peginterferon alfa 2A (40 kD) (PEGASYS) alone or in combination with ribavirin (Copegus): results of an ongoing long-term follow-up study,” Hepatology, vol. 40, supplement 1, p. 400A, 2004. View at Google Scholar
  115. B. J. Veldt, G. Saracco, C. Cammà et al., “Long term clinical outcome of chronic hepatitis C patients with sustained virological response to interferon monotherapy,” Gut, vol. 53, no. 10, pp. 1504–1508, 2004. View at Publisher · View at Google Scholar · View at Scopus
  116. A. Ciancio, A. Smedile, C. Giordanino et al., “Long-term follow-up of previous hepatitis C virus positive nonresponders to interferon monotherapy successfully retreated with combination therapy: are they really cured?” American Journal of Gastroenterology, vol. 101, no. 8, pp. 1811–1816, 2006. View at Publisher · View at Google Scholar · View at Scopus
  117. D. Chavalitdhamrong and T. Tanwandee, “Long-term outcomes of chronic hepatitis C patients with sustained virological response at 6 months after the end of treatment,” World Journal of Gastroenterology, vol. 12, no. 34, pp. 5532–5535, 2006. View at Google Scholar · View at Scopus
  118. E. J. Heathcote, M. L. Shiffman, W. G. E. Cooksley et al., “Peginterferon alfa-2a in patients with chronic hepatitis C and cirrhosis,” The New England Journal of Medicine, vol. 343, no. 23, pp. 1673–1680, 2000. View at Publisher · View at Google Scholar · View at Scopus
  119. M. P. Manns, J. G. McHutchison, S. C. Gordon et al., “Peginterferon alfa-2b plus ribavirin compared with interferonalfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial,” The Lancet, vol. 358, no. 9286, pp. 958–965, 2001. View at Publisher · View at Google Scholar · View at Scopus
  120. M. W. Fried, M. L. Shiffman, K. R. Reddy et al., “Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection,” The New England Journal of Medicine, vol. 347, no. 13, pp. 975–982, 2002. View at Publisher · View at Google Scholar · View at Scopus
  121. S. J. Hadziyannis, H. Sette Jr., T. R. Morgan et al., “Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose,” Annals of Internal Medicine, vol. 140, no. 5, pp. 346–I67, 2004. View at Google Scholar · View at Scopus
  122. S. Zeuzem, R. Hultcrantz, M. Bourliere et al., “Peginterferon alfa-2b plus ribavirin for treatment of chronic hepatitis C in previously untreated patients infected with HCV genotypes 2 or 3,” Journal of Hepatology, vol. 40, no. 6, pp. 993–999, 2004. View at Publisher · View at Google Scholar · View at Scopus