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Does HCV antiviral therapy decrease the risk of hepatocellular carcinoma?

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Abstract

Whether antiviral therapy for hepatitis C virus (HCV) infection can prevent hepatocellular carcinoma (HCC) independent of a sustained virologic response (SVR) has been debated since a randomized trial from Japan in 1995. Incidence of HCC in patients with chronic hepatitis C with SVR is reduced through cirrhosis prevention, but HCC is also prevented in cirrhosis by reduction of necroinflammatory activity and possibly cell turnover. However, HCV patients with cirrhosis who achieve an SVR still have a risk, although a lower one, of HCC, so surveillance must continue. The potential antiproliferative effect of interferon (IFN) with respect to HCC has been discounted by a prospective randomized clinical trial in nonresponders to IFN (Hepatitis C Antiviral Long-term Treatment Against Cirrhosis [HALT-C]), in which IFN did not modify any outcomes. Thus, the best strategy to reduce HCC is to treat HCV-infected patients before they develop cirrhosis and to increase the SVR rate.

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References and Recommended Reading

  1. Perz JF, Armstrong GL, Farrington LA, et al.: The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol 2006, 45:529–538.

    Article  PubMed  Google Scholar 

  2. Poynard T, Yuen MF, Ratziu V, et al.: Viral hepatitis C. Lancet 2003, 362:2095–2100.

    Article  PubMed  CAS  Google Scholar 

  3. Benvegnu L, Gios M, Boccato S, et al.: Natural history of compensated viral cirrhosis: a prospective study on the incidence and hierarchy of major complications. Gut 2004, 53:744–749.

    Article  PubMed  CAS  Google Scholar 

  4. Goodgame B, Shaheen NJ, Galanko J, et al.: The risk of end stage liver disease and hepatocellular carcinoma among persons infected with hepatitis C virus: publication bias? Am J Gastroenterol 2003, 98:2535–2542.

    Article  PubMed  Google Scholar 

  5. Fattovich G, Stroffolini T, Zagni I, et al.: Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology 2004, 127(5 Suppl 1):S35–S50.

    Article  PubMed  Google Scholar 

  6. Shibata M, Morizane T, Uchida T, et al.: Irregular regeneration of hepatocytes and risk of hepatocellular carcinoma in chronic hepatitis and cirrhosis with hepatitis-C-virus infection. Lancet 1998, 351:1773–1777.

    Article  PubMed  CAS  Google Scholar 

  7. Liang TJ, Heller T: Pathogenesis of hepatitis C-associated hepatocellular carcinoma. Gastroenterology 2004, 127(5 Suppl 1):S62–S71.

    Article  PubMed  CAS  Google Scholar 

  8. Moriya K, Fujie H, Shintani Y, et al.: The core protein of hepatitis C virus induces hepatocellular carcinoma in transgenic mice. Nat Med 1998, 4:1065–1087.

    Article  PubMed  CAS  Google Scholar 

  9. N’Kontchou G, Paries J, Htar MT, et al.: Risk factors for hepatocellular carcinoma in patients with alcoholic or viral C cirrhosis. Clin Gastroenterol Hepatol 2006, 4:1062–1068.

    Article  PubMed  Google Scholar 

  10. Marrero CR, Marrero JA: Viral hepatitis and hepatocellular carcinoma. Arch Med Res 2007, 38:612–620.

    Article  PubMed  CAS  Google Scholar 

  11. Tilg H: New insights into the mechanisms of interferon alpha: an immunoregulatory and anti-inflammatory cytokine. Gastroenterology 1997, 112:1017–1021.

    Article  PubMed  CAS  Google Scholar 

  12. Lim R, Knight B, Patel K, et al.: Antiproliferative effects of interferon alpha on hepatic progenitor cells in vitro and in vivo. Hepatology 2006, 43:1074–1083.

    Article  PubMed  CAS  Google Scholar 

  13. Yoshida H, Shiratori Y, Moriyama M, et al.: Interferon therapy reduces the risk for hepatocellular carcinoma: national surveillance program of cirrhotic and noncirrhotic patients with chronic hepatitis C in Japan. IHIT Study Group. Inhibition of Hepatocarcinogenesis by Interferon Therapy. Ann Intern Med 1999, 131:174–181.

    PubMed  CAS  Google Scholar 

  14. Ikeda K, Saitoh S, Arase Y, et al.: Effect of interferon therapy on hepatocellular carcinogenesis in patients with chronic hepatitis type C: a long-term observation study of 1643 patients using statistical bias correction with proportional hazard analysis. Hepatology 1999, 29:1124–1130.

    Article  PubMed  CAS  Google Scholar 

  15. Lindsay KL, Trepo C, Heintges T, et al.: A randomized, double-blind trial comparing pegylated interferon alpha-2b to interferon alpha-2b as initial treatment for chronic hepatitis C. Hepatology 2001, 34:395–403.

    Article  PubMed  CAS  Google Scholar 

  16. Manns MP, McHutchison JG, Gordon SC, et al.: Peginterferon alpha-2b plus ribavirin compared with interferon alpha-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 2001, 358:958–965.

    Article  PubMed  CAS  Google Scholar 

  17. Heathcote EJ: Prevention of hepatitis C virus-related hepatocellular carcinoma. Gastroenterology 2004, 127(5 Suppl 1):S294–S302.

    Article  PubMed  Google Scholar 

  18. Sharara AI, Hunt CM, Hamilton JD: Hepatitis C. Ann Intern Med 1996, 125:658–668.

    PubMed  CAS  Google Scholar 

  19. Wright TL: Treatment of patients with hepatitis C and cirrhosis. Hepatology 2002, 36(5 Suppl 1):S185–S194.

    Article  PubMed  Google Scholar 

  20. Imai Y, Kawata S, Tamura S, et al.: Relation of interferon therapy and hepatocellular carcinoma in patients with chronic hepatitis C. Osaka Hepatocellular Carcinoma Prevention Study Group. Ann Intern Med 1998, 129:94–99.

    PubMed  CAS  Google Scholar 

  21. Shindo M, Ken A, Okuno T: Varying incidence of cirrhosis and hepatocellular carcinoma in patients with chronic hepatitis C responding differently to interferon therapy. Cancer 1999, 85:1943–1950.

    PubMed  CAS  Google Scholar 

  22. Okanoue T, Itoh Y, Minami M, et al.: Interferon therapy lowers the rate of progression to hepatocellular carcinoma in chronic hepatitis C but not significantly in an advanced stage: a retrospective study in 1148 patients. Viral Hepatitis Therapy Study Group. J Hepatol 1999, 30:653–659.

    Article  PubMed  CAS  Google Scholar 

  23. Camma C, Giunta M, Andreone P, et al.: Interferon and prevention of hepatocellular carcinoma in viral cirrhosis: an evidence-based approach. J Hepatol 2001, 34:593–602.

    Article  PubMed  CAS  Google Scholar 

  24. Papatheodoridis GV, Papadimitropoulos VC, Hadziyannis SJ: Effect of interferon therapy on the development of hepatocellular carcinoma in patients with hepatitis C virus-related cirrhosis: a meta-analysis. Aliment Pharmacol Ther 2001, 15:689–698.

    Article  PubMed  CAS  Google Scholar 

  25. Nishiguchi S, Kuroki T, Nakatani S, et al.: Randomised trial of effects of interferon-alpha on incidence of hepatocellular carcinoma in chronic active hepatitis C with cirrhosis. Lancet 1995, 346:1051–1055.

    Article  PubMed  CAS  Google Scholar 

  26. Valla DC, Chevallier M, Marcellin P, et al.: Treatment of hepatitis C virus-related cirrhosis: a randomized, controlled trial of interferon alpha-2b versus no treatment. Hepatology 1999, 29:1870–1875.

    Article  PubMed  CAS  Google Scholar 

  27. Mura D, Delliperi R, Fastame L, et al.: Five years follow-up after interferon therapy in HCV-positive compensated cirrhosis. Ital J Gastroenterol Hepatol 1998, 30:A114.

    Google Scholar 

  28. Bernardinello E, Cavalletto L, Chemello L, et al.: Longterm clinical outcome after beta-interferon therapy in cirrhotic patients with chronic hepatitis C. TVVH Study Group. Hepatogastroenterology 1999, 46:3216–3222.

    PubMed  CAS  Google Scholar 

  29. Nishiguchi S, Shiomi S, Nakatani S, et al.: Prevention of hepatocellular carcinoma in patients with chronic active hepatitis C and cirrhosis. Lancet 2001, 357:196–197.

    Article  PubMed  CAS  Google Scholar 

  30. Bruno S, Stroffolini T, Colombo M, et al.: Sustained virological response to interferon-alpha is associated with improved outcome in HCV-related cirrhosis: a retrospective study. Hepatology 2007, 45:579–587.

    Article  PubMed  CAS  Google Scholar 

  31. Bruix J, Sherman M, Llovet JM, et al.: EASL Panel of Experts on HCC: Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol 2001, 35:421–430.

    Article  PubMed  CAS  Google Scholar 

  32. 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.

    PubMed  Google Scholar 

  33. Arase Y, Ikeda K, Suzuki F, et al.: Prolonged-interferon therapy reduces hepatocarcinogenesis in aged-patients with chronic hepatitis C. J Med Virol 2007, 79:1095–1102.

    Article  PubMed  CAS  Google Scholar 

  34. Murashima S, Tanaka M, Haramaki M, et al.: A decrease in AFP level related to administration of interferon in patients with chronic hepatitis C and a high level of AFP. Dig Dis Sci 2006, 51:808–812.

    Article  PubMed  CAS  Google Scholar 

  35. Braks RE, Ganne-Carrie N, Fontaine H, et al.: Effect of sustained virological response on long-term clinical outcome in 113 patients with compensated hepatitis C-related cirrhosis treated by interferon alpha and ribavirin. World J Gastroenterol 2007, 13:5648–5653.

    PubMed  Google Scholar 

  36. Di Bisceglie AM, Shiffman M, Everson GT, et al.: Prolonged antiviral therapy with peginterferon to prevent complications of advanced liver disease associated with hepatitis C: results of the hepatitis C antiviral long-term treatment against cirrhosis (HALT-C) trial [abstract]. Hepatology 2007, 46(Suppl 1):LB1.

    Google Scholar 

  37. Fartoux L, Degos F, Trepo C, et al.: Effect of prolonged interferon therapy on the outcome of hepatitis C virus-related cirrhosis: a randomized trial. Clin Gastroenterol Hepatol 2007, 5:502–507.

    Article  PubMed  CAS  Google Scholar 

  38. Afdhal N, Freilich B, Levine R, et al.: Colchicine versus peg-intron long term (COPILOT) trial: interim analysis of clinical outcomes at year 2 [abstract 171]. Hepatology 2004, 40:239A.

    Article  Google Scholar 

  39. Swain MG, Lai MY, Shiffman ML, et al.: Durable sustained virological response after treatment with peginterferon alpha-2a alone or in combination with ribavirin: 5-year follow-up and the criteria of a cure. J Hepatol 2007, 46(Suppl 1):S3.

    Article  Google Scholar 

  40. Pradat P, Tillmann HL, Sauleda S, et al.: Long-term follow-up of the hepatitis C HENCORE cohort: response to therapy and occurrence of liver-related complications. J Viral Hepat 2007, 14:556–563.

    Article  PubMed  CAS  Google Scholar 

  41. Arase Y, Ikeda K, Suzuki F, et al.: Interferon-induced prolonged biochemical response reduces hepatocarcinogenesis in hepatitis C virus infection. J Med Virol 2007, 79:1485–1490.

    Article  PubMed  CAS  Google Scholar 

  42. Gramenzi A, Andreone P, Fiorino S, et al.: Impact of interferon therapy on the natural history of hepatitis C virus related cirrhosis. Gut 2001, 48:843–848.

    Article  PubMed  CAS  Google Scholar 

  43. Chen TM, Huang PT, Tsai MH, et al.: Predictors of alpha-fetoprotein elevation in patients with chronic hepatitis C, but not hepatocellular carcinoma, and its normalization after pegylated interferon alpha 2a-ribavirin combination therapy. J Gastroenterol Hepatol 2007, 22:669–675.

    PubMed  CAS  Google Scholar 

  44. Yamaura T, Matsumoto A, Rokuhara A, et al.: Development of small hepatocellular carcinoma in a patient with chronic hepatitis C after 77 months of a sustained and complete response to interferon therapy. J Gastroenterol Hepatol 2002, 17:1229–1235.

    Article  PubMed  Google Scholar 

  45. Kobayashi S, Takeda T, Enomoto M, 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 Int 2007, 27:186–191.

    Article  PubMed  CAS  Google Scholar 

  46. Okanoue T, Itoh Y: Hepatocellular carcinoma in sustained responders of interferon-treated chronic hepatitis C. J Gastroenterol Hepatol 2003, 18:121–123.

    Article  PubMed  Google Scholar 

  47. Cacciola I, Pollicino T, Squadrito G, et al.: Occult hepatitis B virus infection in patients with chronic hepatitis C liver disease. N Engl J Med 1999, 341:22–26.

    Article  PubMed  CAS  Google Scholar 

  48. Sheu JC, Huang GT, Shih LN, et al.: Hepatitis C and B viruses in hepatitis B surface antigen-negative hepatocellular carcinoma. Gastroenterology 1992, 103:1322–1327.

    PubMed  CAS  Google Scholar 

  49. Ikeda K, Marusawa H, Osaki Y, et al.: Antibody to hepatitis B core antigen and risk for hepatitis C-related hepatocellular carcinoma: a prospective study. Ann Intern Med 2007, 146:649–656.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Liver Transplant and Hepatobiliary Unit, Royal Free Hospital, Pond Street, Hampstead, NW3 2QG, London, UK

    Andrew K. Burroughs

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  1. Maria Pleguezuelo
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  2. Laura Marelli
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  3. Sergio Maimone
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  4. Pinelopi Manousou
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  5. Elias Xirouchakis
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  6. Andrew K. Burroughs
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Correspondence to Andrew K. Burroughs.

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Pleguezuelo, M., Marelli, L., Maimone, S. et al. Does HCV antiviral therapy decrease the risk of hepatocellular carcinoma?. Curr hepatitis rep 7, 72–80 (2008). https://doi.org/10.1007/s11901-008-0011-5

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