Current Hepatitis Reports

, Volume 8, Supplement 1, pp 35–42 | Cite as

Erratum to: The Role of Interferon Therapy in Patients With Hepatocellular Carcinoma


Interferon (IFN) not only may have antiviral properties against hepatitis C, but also may reduce the risk of hepatocellular carcinoma (HCC) through anticarcinogenic properties or indirectly by antifibrotic effects. Because patients with chronic hepatitis C and cirrhosis are at risk for HCC, IFN was used to prevent or treat HCC in patients with hepatitis C. Studies demonstrate that the risk of HCC in hepatitis C patients who are sustained viral responders is substantially reduced but not eliminated. The Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis trial demonstrated that maintenance therapy with IFN does not reduce the risk of HCC in patients with bridging fibrosis or cirrhosis. Other studies suggest the risk of HCC is reduced with IFN maintenance therapy in older patients or in patients whose α-fetoprotein levels decline. A randomized clinical trial demonstrated IFN therapy is not effective against HCC. Few studies suggest IFN may reduce the risk of recurrent HCC or reduce tumor burden after ablation or resection. Larger trials are needed to determine if IFN can prevent tumor recurrence after resection or locoregional therapy in patients with hepatitis C cirrhosis and HCC.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Llovet JM, Ricci S, Mazzaferro V, et al.: Sorafenib in advanced hepatocellular carcinoma. New Engl J Med 2008, 359:378–390.PubMedCrossRefGoogle Scholar
  2. 2.
    El-Serag H, Rudolph L: Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 2007, 132:2557–2576.PubMedCrossRefGoogle Scholar
  3. 3.
    Hino O: Understanding hypercarcinogenic state in chronic hepatitis: a clue to the prevention of human hepatocellular carcinoma. J Gastroenterol 2002, 37:883–887.PubMedCrossRefGoogle Scholar
  4. 4.
    Matsuzaki K, Murata M, Yoshida K, et al.: Chronic inflammation associated with hepatitis C virus infection perturbs hepatic transforming growth factor signaling promoting cirrhosis and hepatocellular carcinoma. Hepatology 2007, 46:48–57.PubMedCrossRefGoogle Scholar
  5. 5.
    Schulze-Krebs A, Preimel D, Popov Y, et al.: Hepatitis C virus-replicating hepatocytes induce fibrogenic activation of hepatic stellate cells. Gastroenterology 2005, 129:246–248.PubMedCrossRefGoogle Scholar
  6. 6.
    Moriye K, Fujiie H, Shintani Y, et al. The core protein of hepatitis C virus induces hepatocellular carcinoma in transgenic mice. Nat Med. 1998;4:1065–7.CrossRefGoogle Scholar
  7. 7.
    Khan F, Peltekian KM, Peterson TC: Effect of interferonalpha, ribavirin, pentoxyfylline, and interleukin-18 antibody on hepatitis C sera-stimulated hepatic stellate cell proliferation. J Interferon Cytokine Res 2008, 28:643–651.PubMedCrossRefGoogle Scholar
  8. 8.
    Tasci I, Mas MR, Vural SR, et al. Rat liver fibrosis regresses better with pegylated interferon alpha-2b and ursodeoxycholic acid treatments than spontaneous recovery. Liver Int. 2006;26:261–8.PubMedCrossRefGoogle Scholar
  9. 9.
    Wang L, Wu WZ, Sun HC, et al.: Mechanism of interferon alpha on inhibition of metastasis and angiogenesis of hepatocellular carcinoma after curative resection in nude mice. J Gastrointest Surg 2003, 7:587–594.PubMedCrossRefGoogle Scholar
  10. 10.
    Cao B, Chen XP, Zhu P, et al.: Inhibitory effect of interferon-alpha-2b on expression of cyclooxygenase-2 and vascular endothelial growth factor in human hepatocellular carcinoma inoculated nude mice. World J Gastroenterol 2008, 14:6802–6807.PubMedCrossRefGoogle Scholar
  11. 11.
    Nakamura M, Nagano H, Sakon M, et al.: Role of the Fas/FasL pathway in combination therapy with interferon-alpha and fluorouracil against hepatocellular carcinoma in vitro. J Hepatol 2007, 46:77–88.PubMedCrossRefGoogle Scholar
  12. 12.
    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.PubMedCrossRefGoogle Scholar
  13. 13.
    MacParland SA, Pham TNQ, Guy CS, Michalak TI: Hepatitis C virus persisting after clinically apparent sustained virological response to antiviral therapy retains infectivity in vitro. Hepatology 2009, 49:1431–1441.PubMedCrossRefGoogle Scholar
  14. 14.
    Hayashi T, Tamori A, Nishikawa M, et al.: Differences in molecular alterations of hepatocellular carcinoma between patients with a sustained viral response and those with hepatitis C virus infection. Liver Int 2009, 29:126–132.PubMedCrossRefGoogle Scholar
  15. 15.
    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.PubMedGoogle Scholar
  16. 16.
    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.PubMedCrossRefGoogle Scholar
  17. 17.
    Ikeda K, Saitoh S, Arase Y, et al.: Effect of interferon therapy on hepatocellular carcinogenesis in patients with chronic hepatitis C: A long-term observation study of 1,643 patients using statistical bias correction with proportional hazard analysis. Hepatology 1999, 29:1124–1130.PubMedCrossRefGoogle Scholar
  18. 18.
    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. Ann Intern Med 1999, 131:174–181.PubMedGoogle Scholar
  19. 19.
    Imai Y, Kawata S, Tamura S, et al.: Relation of interferon therapy and hepatocellular carcinoma in patients with chronic hepatitis C. Ann Intern Med 1998, 129:94–99.PubMedGoogle Scholar
  20. 20.
    Sanefuji K, Kayashima H, Iguchi T, et al.: Characterization of hepatocellular carcinoma developed after achieving sustained virological response to interferon therapy for hepatitis C. J Surg Oncol 2009, 99:32–37.PubMedCrossRefGoogle Scholar
  21. 21.
    Shiffman ML, Hofmann CM, Contos MJ, et al.: A randomized, controlled trial of maintenance interferon for patients with chronic hepatitis C virus and persistent viremia. Gastroenterology 1999, 117:1164–1172.PubMedCrossRefGoogle Scholar
  22. 22.
    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.PubMedCrossRefGoogle Scholar
  23. 23.
    Di Bisceglie AM, Shiffman ML, Everson GT, et al.: Prolonged therapy of advanced chronic hepatitis C with lowdose peginterferon. N Engl J Med 2008, 359:2429–2441.PubMedCrossRefGoogle Scholar
  24. 24.•
    Lok AS, Seeff LB, Morgan TR, et al.: Incidence of hepatocellular carcinoma and associated risk factors in hepatitis C-related advanced liver disease. Gastroenterology 2009, 136:138–148. This article presents a detailed analysis from the HALT-C trial on risk of HCC in maintenance IFN and control groups. No significant difference in rate of HCC was found between the two groups.PubMedCrossRefGoogle Scholar
  25. 25.
    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.PubMedCrossRefGoogle Scholar
  26. 26.
    Tamura Y, Tamagiwa S, Aoki Y, et al.: Serum alpha-fetoprotein levels during and after interferon therapy and the development of hepatocellular carcinoma in patients with chronic hepatitis C. Dig Dis Sci 2008 (Epub ahead of print).Google Scholar
  27. 27.
    Fartoux L, Degos F, Trepo C, et al.: Effect of prolonged interferon therapy on the outcome of hepatitis C virusrelated cirrhosis:a randomized trial. Clin Gastroenterol Hepatol 2007, 5:502–507.PubMedCrossRefGoogle Scholar
  28. 28.
    Patt YZ, Yoffe B, Charnsangavej C, et al.: Low serum alpha-fetoprotein level in patients with hepatocellular carcinoma as a predictor of response to 5-FU and interferon-alpha-2b. Cancer 1993, 72:2574–2582.PubMedCrossRefGoogle Scholar
  29. 29.
    Lai CL, Lau JYN, Wu PC, et al. Recombinant interferon alpha in inoperable hepatocellular carcinoma: a randomized controlled trial. Hepatology. 1993;17:389–94.PubMedCrossRefGoogle Scholar
  30. 30.
    Llovet JM, Sala M, Castells L, et al.: Randomized controlled trial of interferon treatment for advanced hepatocellular carcinoma. Hepatology 2000, 31:54–58.PubMedCrossRefGoogle Scholar
  31. 31.
    Uenishi T, Nishiguchi S, Tanaka S, et al.: Response to interferon therapy affects risk factors for postoperative recurrence of hepatitis C virus-related hepatocellular carcinoma. J Surg Oncol 2008, 98:358–362.PubMedCrossRefGoogle Scholar
  32. 32.•
    Mazzaferro V, Romito R, Schiavo M, et al.: Prevention of hepatocellular carcinoma recurrence with alpha-interferon after liver resection in HCV cirrhosis. Hepatology 2006, 44:1543–1554. This randomized study of IFN after resection of HCC in HCV cirrhotic patients demonstrated no overall benefit with IFN. The subgroup of hepatitis C patients who were hepatitis B core antibody negative and were treated with IFN had lower recurrence rates.PubMedCrossRefGoogle Scholar
  33. 33.
    Nagano H, Miyamoto A, Wada H, et al.: Interferon-alfa and 5-fluorouracil combination therapy after palliative hepatic resection in patients with advanced hepatocellular carcinoma, portal venous tumor thrombus in the major trunk and multiple nodules. Cancer 2007, 110:2493–2501.PubMedCrossRefGoogle Scholar
  34. 34.
    Liang LJ, Hu WJ, Yin XY, et al.: Adjuvant intraportal venous chemotherapy for patients with hepatocellular carcinoma and portal vein tumor thrombi following hepatectomy plus portal thrombectomy. World J Surg 2008, 32:627–631.PubMedCrossRefGoogle Scholar
  35. 35.
    Ikeda K, Arase Y, Saitoh S, et al.: Interferon beta prevents recurrence of hepatocellular carcinoma after complete resection or ablation of the primary tumor: a prospective randomized study of hepatitis C virus–related liver cancer. Hepatology 2000, 32:228–232.PubMedCrossRefGoogle Scholar
  36. 36.
    Shiratori Y, Shiina S, Teratani, et al.: Interferon therapy after tumor ablation improves prognosis in patients with hepatocellular carcinoma associated with hepatitis C virus. Ann Intern Med 2003, 138:299–306.PubMedGoogle Scholar
  37. 37.
    Jeong S, Aikata H, Katamura Y, et al.: Low-dose intermittent interferon-alpha therapy for HCV-related liver cirrhosis after curative treatment of hepatocellular carcinoma. World J Gastroenterol 2007, 13:5188–5195.PubMedGoogle Scholar
  38. 38.
    Kudo M: Impact of interferon therapy after curative treatment of hepatocellular carcinoma. Oncology 2008, 75(Suppl 1):30–41.PubMedCrossRefGoogle Scholar
  39. 39.
    Kubo S, Nishiguchi S, Hirohashi K, et al.: Randomized clinical trial of long-term outcome after resection of hepatitis C virus-related hepatocellular carcinoma by postoperative interferon therapy. Br J Surg 2002, 89:418–422.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Division of TransplantationCarolinas Medical CenterCharlotteUSA

Personalised recommendations