Current Hepatitis Reports

, Volume 8, Supplement 1, pp 1–7

Hepatitis C Virus and Cancers: How Strong Is the Relationship?

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Non–liver-related malignancies are increasingly seen in patients infected with hepatitis C virus (HCV). Whether this phenomenon is related to the increasing prevalence of chronic hepatitis C (CHC) or to a direct causal role by HCV is unknown. Until recently, most of the evidence supporting the association between these cancers and HCV was based on small and heterogeneous epidemiologic studies. Recent studies addressing this issue are larger; however, they remain largely observational and have significant limitations. The precise mechanism by which HCV causes these malignancies is under investigation, but several studies demonstrated that antiviral therapy can reduce the risk of some malignancies and can increase tumor-free survival following successful tumor-directed therapy. Thus, the role of antiviral therapy for CHC could possibly be expanded to include treatment of certain subgroups of patients with the associated cancers if HCV is identified as a causative agent of these malignancies.

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  1. 1.
    Butel JS: Viral carcinogenesis: revelation of molecular mechanisms and etiology of human disease. Carcinogenesis 2000, 21:405–426.PubMedCrossRefGoogle Scholar
  2. 2.
    Armstrong GL, Wasley A, Simard EP, et al.: The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann Intern Med 2006, 144:705–714.PubMedGoogle Scholar
  3. 3.
    Hill AB: The environment and disease: association or causation? Proc R Soc Med 1965, 58:295–300.PubMedGoogle Scholar
  4. 4.
    Anderson LA, Engels EA: Hepatitis C virus infection and non-Hodgkin lymphoma: interesting association or causal relationship? Int J Cancer 2008, 122:x–xii.PubMedCrossRefGoogle Scholar
  5. 5.
    Misiani R, Bellavita P, Fenili D, et al.: Hepatitis C virus infection in patients with essential mixed cryoglobulinemia. Ann Intern Med 1992, 117:573–577.PubMedGoogle Scholar
  6. 6.
    Agnello V, Chung RT, Kaplan LM: A role for hepatitis C virus infection in type II cryoglobulinemia. N Engl J Med 1992, 327:1490–1495.PubMedCrossRefGoogle Scholar
  7. 7.
    Mazzaro C, Tirelli U, Pozzato G: Hepatitis C virus and non-Hodgkin’s lymphoma 10 years later. Dig Liver Dis 2005, 37:219–226.PubMedCrossRefGoogle Scholar
  8. 8.•
    Giordano TP, Henderson L, Landgren O, et al.: Risk of non-Hodgkin lymphoma and lymphoproliferative precursor diseases in US veterans with hepatitis C virus. JAMA 2007, 297:2010–2017. This article describes a landmark cohort study that helped confirm associations and establish temporal relationships between HCV and some diseases of interest. PubMedCrossRefGoogle Scholar
  9. 9.
    Racanelli V, Sansonno D, Piccoli C, et al.: Molecular characterization of B cell clonal expansions in the liver of chronically hepatitis C virus-infected patients. J Immunol 2001, 167:21–29.PubMedGoogle Scholar
  10. 10.
    Bigot-Corbel E, Gassin M, Corre I, et al.: Hepatitis C virus (HCV) infection, monoclonal immunoglobulin specific for HCV core protein, and plasma-cell malignancy. Blood 2008, 112:4357–4358.PubMedCrossRefGoogle Scholar
  11. 11.
    Misiani R, Bellavita P, Fenili D, et al.: Interferon alfa-2a therapy in cryoglobulinemia associated with hepatitis C virus. N Engl J Med 1994, 330:751–756.PubMedCrossRefGoogle Scholar
  12. 12.
    D’Amico E, Chincoli C, Cacciatore P, et al.: Effects of combined antiviral therapy on asymptomatic mixed cryoglobulinemia in naive patients with chronic hepatitis C virus infection: a preliminary study. Dig Dis Sci 2005, 50:2344–2347.PubMedCrossRefGoogle Scholar
  13. 13.
    Cacoub P, Lidove O, Maisonobe T, et al.: Interferon-alpha and ribavirin treatment in patients with hepatitis C virus-related systemic vasculitis. Arthritis Rheum 2002, 46:3317–3326.PubMedCrossRefGoogle Scholar
  14. 14.
    Leleu X, O’Connor K, Ho AW, et al.: Hepatitis C viral infection is not associated with Waldenstrom’s macroglobulinemia. Am J Hematol 2007, 82:83–84.PubMedCrossRefGoogle Scholar
  15. 15.
    Neri S, Pulvirenti D, Mauceri B, et al.: A case of progression from type II cryoglobulinaemia to Waldenstrom’s macroglobulinaemia in a patient with chronic hepatitis C. Clin Exp Med 2005, 5:40–42.PubMedCrossRefGoogle Scholar
  16. 16.
    Dal Maso L, Franceschi S: Hepatitis C virus and risk of lymphoma and other lymphoid neoplasms: a meta-analysis of epidemiologic studies. Cancer Epidemiol Biomarkers Prev 2006, 15:2078–2085.CrossRefGoogle Scholar
  17. 17.
    Nieters A, Kallinowski B, Brennan P, et al.: Hepatitis C and risk of lymphoma: results of the European multicenter case-control study EPILYMPH. Gastroenterology 2006, 131:1879–1886.PubMedCrossRefGoogle Scholar
  18. 18.•
    de Sanjose S, Benavente Y, Vajdic CM, et al.: Hepatitis C and non-Hodgkin lymphoma among 4784 cases and 6269 controls from the International Lymphoma Epidemiology Consortium. Clin Gastroenterol Hepatol 2008, 6:451–458. This article describes a large, multinational, case-control study that provided key evidence for an association between HCV and non-Hodgkin lymphoma. PubMedCrossRefGoogle Scholar
  19. 19.
    Rosa D, Saletti G, De Gregorio E, et al.: Activation of naive B lymphocytes via CD81, a pathogenetic mechanism for hepatitis C virus-associated B lymphocyte disorders. Proc Natl Acad Sci U S A 2005, 102:18544–18549.PubMedCrossRefGoogle Scholar
  20. 20.
    Novak AJ, Grote DM, Stenson M, et al.: Expression of BLyS and its receptors in B-cell non-Hodgkin lymphoma: correlation with disease activity and patient outcome. Blood 2004, 104:2247–2253.PubMedCrossRefGoogle Scholar
  21. 21.
    Machida K, Cheng KT, Pavio N, et al.: Hepatitis C virus E2-CD81 interaction induces hypermutation of the immunoglobulin gene in B cells. J Virol 2005, 79:8079–8089.PubMedCrossRefGoogle Scholar
  22. 22.
    Mazzaro C, Franzin F, Tulissi P, et al.: Regression of monoclonal B-cell expansion in patients affected by mixed cryoglobulinemia responsive to alpha-interferon therapy. Cancer 1996, 77:2604–2613.PubMedCrossRefGoogle Scholar
  23. 23.
    Hermine O, Lefrere F, Bronowicki JP, et al.: Regression of splenic lymphoma with villous lymphocytes after treatment of hepatitis C virus infection. N Engl J Med 2002, 347:89–94.PubMedCrossRefGoogle Scholar
  24. 24.
    Gisbert JP, Garcia-Buey L, Pajares JM, Moreno-Otero R: Systematic review: regression of lymphoproliferative disorders after treatment for hepatitis C infection. Aliment Pharmacol Ther 2005, 21:653–662.PubMedCrossRefGoogle Scholar
  25. 25.
    La Mura V, De Renzo A, Perna F, et al.: Antiviral therapy after complete response to chemotherapy could be efficacious in HCV-positive non-Hodgkin’s lymphoma. J Hepatol 2008, 49:557–563.PubMedCrossRefGoogle Scholar
  26. 26.
    Kawamura Y, Ikeda K, Arase Y, et al.: Viral elimination reduces incidence of malignant lymphoma in patients with hepatitis C. Am J Med 2007, 120:1034–1041.PubMedCrossRefGoogle Scholar
  27. 27.
    Yamamoto S, Kubo S, Hai S, et al.: Hepatitis C virus infection as a likely etiology of intrahepatic cholangiocarcinoma. Cancer Sci 2004, 95:592–595.PubMedCrossRefGoogle Scholar
  28. 28.
    Donato F, Gelatti U, Tagger A, et al.: Intrahepatic cholangiocarcinoma and hepatitis C and B virus infection, alcohol intake, and hepatolithiasis: a case-control study in Italy. Cancer Causes Control 2001, 12:959–964.PubMedCrossRefGoogle Scholar
  29. 29.
    Welzel TM, Graubard BI, El-Serag HB, et al.: Risk factors for intrahepatic and extrahepatic cholangiocarcinoma in the United States: a population-based case-control study. Clin Gastroenterol Hepatol 2007, 5:1221–1228.PubMedCrossRefGoogle Scholar
  30. 30.
    Takagi K, Nishikawa S, Nagasaka A, et al.: Malignant lymphoma of the pancreas with chronic hepatitis C [in Japanese]. Nippon Shokakibyo Gakkai Zasshi 2004, 101:1227–1231.PubMedGoogle Scholar
  31. 31.
    Alvares-Da-Silva MR, Francisconi CF, Waechter FL: Acute hepatitis C complicated by pancreatitis: another extrahepatic manifestation of hepatitis C virus? J Viral Hepat 2000, 7:84–86.PubMedCrossRefGoogle Scholar
  32. 32.•
    El-Serag HB, Engels EA, Landgren O, et al.: Risk of hepatobiliary and pancreatic cancers after hepatitis C virus infection: a population-based study of US veterans. Hepatology 2009, 49:116–123. This article describes a large, US cohort study of the association of HCV and pancreaticohepatobiliary cancers. PubMedCrossRefGoogle Scholar
  33. 33.
    Lee CH, Chang CJ, Lin YJ, et al.: Viral hepatitis-associated intrahepatic cholangiocarcinoma shares common disease processes with hepatocellular carcinoma. Br J Cancer 2009, 100:1765–1770.PubMedCrossRefGoogle Scholar
  34. 34.
    Perumal V, Wang J, Thuluvath P, et al.: Hepatitis C and hepatitis B nucleic acids are present in intrahepatic cholangiocarcinomas from the United States. Hum Pathol 2006, 37:1211–1216.PubMedCrossRefGoogle Scholar
  35. 35.
    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
  36. 36.
    Yoffe B, Bagri AS, Tran T, et al.: Hyperlipasemia associated with hepatitis C virus. Dig Dis Sci 2003, 48:1648–1653.PubMedCrossRefGoogle Scholar
  37. 37.
    Kaya A, Kanbay M, Bayrak O, et al.: Primary renal lymphoma associated with hepatitis C virus infection. Leuk Lymphoma 2006, 47:1976–1978.PubMedCrossRefGoogle Scholar
  38. 38.
    Garcia JH, Coelho GR, Cavalcante FP, et al.: Synchronous hepatocellular carcinoma and renal cell carcinoma in a liver transplant recipient: a case report. Transplantation 2007, 84:1713.PubMedCrossRefGoogle Scholar
  39. 39.
    Antonelli A, Ferri C, Fallahi P, et al.: Thyroid cancer in HCV-related chronic hepatitis patients: a case-control study. Thyroid 2007, 17:447–451.PubMedCrossRefGoogle Scholar
  40. 40.
    Duberg AS, Nordstrom M, Torner A, et al.: Non-Hodgkin’s lymphoma and other nonhepatic malignancies in Swedish patients with hepatitis C virus infection. Hepatology 2005, 41:652–659.PubMedCrossRefGoogle Scholar
  41. 41.
    Antonelli A, Ferri C, Fallahi P, et al.: Thyroid disorders in chronic hepatitis C virus infection. Thyroid 2006, 16:563–572.PubMedCrossRefGoogle Scholar
  42. 42.
    Okayasu I, Saegusa M, Fujiwara M, et al.: Enhanced cellular proliferative activity and cell death in chronic thyroiditis and thyroid papillary carcinoma. J Cancer Res Clin Oncol 1995, 121:746–752.PubMedCrossRefGoogle Scholar
  43. 43.
    Parkin DM: Global cancer statistics in the year 2000. Lancet Oncol 2001, 2:533–543.PubMedCrossRefGoogle Scholar
  44. 44.
    El-Serag HB, Mason AC: Risk factors for the rising rates of primary liver cancer in the United States. Arch Intern Med 2000, 160:3227–3230.PubMedCrossRefGoogle Scholar
  45. 45.
    Davila JA, Morgan RO, Shaib Y, et al.: Hepatitis C infection and the increasing incidence of hepatocellular carcinoma: a population-based study. Gastroenterology 2004, 127:1372–1380.PubMedCrossRefGoogle Scholar
  46. 46.
    Hassan MM, Frome A, Patt YZ, El-Serag HB: Rising prevalence of hepatitis C virus infection among patients recently diagnosed with hepatocellular carcinoma in the United States. J Clin Gastroenterol 2002, 35:266–269.PubMedCrossRefGoogle Scholar
  47. 47.
    Moriya K, Fujie H, Shintani Y, et al.: The core protein of hepatitis C virus induces hepatocellular carcinoma in transgenic mice. Nat Med 1998, 4:1065–1067.PubMedCrossRefGoogle Scholar
  48. 48.
    Camma C, Giunta M, Andreone P, Craxi A: Interferon and prevention of hepatocellular carcinoma in viral cirrhosis: an evidence-based approach. J Hepatol 2001, 34:593–602.PubMedCrossRefGoogle Scholar
  49. 49.
    Di Bisceglie AM, Shiffman ML, Everson GT, et al.: Prolonged therapy of advanced chronic hepatitis C with low-dose peginterferon. N Engl J Med 2008, 359:2429–2441.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Division of Gastroenterology and HepatologyStanford University Medical CenterPalo AltoUSA

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