Review Article | Published:

Extrahepatic cancers and chronic HCV infection

Nature Reviews Gastroenterology & Hepatology volume 15, pages 283290 (2018) | Download Citation


Infectious agents, such as HCV, account for 15% of human cancers. HCV infects not only hepatocytes but also extrahepatic cells. Chronic HCV infection can induce chronic inflammation with qualitative and quantitative alterations of the immune repertoire and tissue microenvironment, which could induce various neoplasias. Epidemiological studies and meta-analyses suggest an increased rate of extrahepatic cancers in patients with chronic HCV infection along with a higher risk of intrahepatic cholangiocarcinoma, pancreatic cancer and non-Hodgkin lymphoma (NHL), highlighting the need to screen for HCV infection in patients with these cancers. Development of B cell NHL has been associated with HCV infection, with a relative risk of 1.5. Direct transformation related to the presence of the virus and chronic antigenic stimulation are the two major non-exclusive mechanisms involved in HCV-related lymphomagenesis. HCV infection alters survival of patients with lymphoma, and sustained virologic response (SVR) substantially improves prognosis. Antiviral treatments might induce remission of indolent lymphoma when SVR is achieved even without chemotherapy, emphasizing the role of HCV in lymphomagenesis in this context. However, studies are needed to provide prospective evidence of a causal relationship between chronic HCV infection and other extrahepatic cancers and to determine whether the risk of extrahepatic cancers is reduced with SVR. In this Review, we report on recent studies analysing the risk of extrahepatic cancers associated with chronic HCV infection. Although there is no doubt regarding the direct and indirect causality between HCV and NHL, an increased risk of other cancers is less clear, with the exception of cholangiocarcinoma.

Key points

  • Chronic HCV infection is a systemic disease resulting in hepatic and extrahepatic manifestations

  • Globally, approximately 15% of human cancers are related to infectious agents such as HCV

  • B cell non-Hodgkin lymphoma (NHL) is associated with HCV infection (relative risk of 1.5) and is related to chronic antigenic stimulation and to a lesser extent to direct transformation associated with virus presence

  • Antiviral therapies enable a sustained virologic and haematological response in two-thirds of patients with HCV-related NHL

  • HCV also infects extrahepatic cells and could induce chronic qualitative and quantitative alterations of the immune repertoire and local tissue microenvironment, which could induce various non-liver cancers

  • Chronic HCV infection is generally accepted to increase the risk of NHL and intrahepatic cholangiocarcinoma, and studies of other cancers that take confounding factors into account are warranted

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Author notes

    • Stanislas Pol
    •  & Anaïs Vallet-Pichard

    These authors contributed equally to this work.


  1. Université Paris Descartes, 12 Rue de l'Ecole de Médecine 75006 Paris, France.

    • Stanislas Pol
  2. Unité d'Hépatologie Hôpital Cochin, 27 rue du faubourg Saint Jacques, 75679 Paris Cedex 14, France.

    • Stanislas Pol
    •  & Anaïs Vallet-Pichard
  3. Centre de Recherche Translationnelle and INSERM U-1223, Institut Pasteur, Paris, 25 Rue du Docteur Roux, 75015 Paris, France.

    • Stanislas Pol
  4. Service d'Hématologie, Hôpital Necker, 147 Rue de Sèvres, 75015 Paris Cedex 15, France.

    • Olivier Hermine


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S.P. and A.V.-P. researched the data and discussed content for the article. S.P. and A.V.-P. contributed equally to writing the article. S.P., A.V.-P. and O.H. reviewed and/or edited the manuscript before submission.

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The authors declare no competing financial interests.

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Correspondence to Stanislas Pol.

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