Hepatitis B and C Virus Infection and Risk of Haematological Malignancies

Aldo Marrone; Marco Ciotti; Luca Rinaldi; Luigi Elio Adinolfi; Marc Ghany


J Viral Hepat. 2019;27(1):4-12. 

In This Article

Abstract and Introduction


Hepatitis B virus (HBV) and hepatitis C virus (HCV) are classified as oncogenic human viruses. Chronic HBV and HCV infections are associated with higher risk of haematological malignancy development. Direct and indirect oncogenic mechanisms have been demonstrated for both HBV and HCV in several studies. HCV and overt/occult HBV infections in patients with oncohaematological disease constitute an impediment and a threat during immunosuppressive chemotherapy treatment. We review the HBV and HCV oncogenic mechanisms and the impact and the safety of antiviral treatment in patients with haematological malignancies.


Approximately 20% of human cancers can be related to infectious agents, including viruses, bacteria and parasites.[1,2] Hepatitis B virus (HBV) and hepatitis C virus (HCV) together with Epstein-Barr virus (EBV), Kaposi's sarcoma herpes virus (KSHV), human immunodeficiency virus, type-1 (HIV-1), human T cell lymphotrophic virus, type-1 (HTLV-1) and some types of human papillomavirus (HPV) are classified as Group 1 oncogenic human viruses according to the International Agency for Research on Cancer (IARC).[3]

Viruses are intracellular pathogens that use the host intracellular machinery to replicate. Oncogenic viruses can induce carcinogenesis via three distinct mechanisms: direct, indirect through chronic inflammation or through immune suppression. Viruses that are directly oncogenic include EBV, HPV, HTLV-1. Their main characteristics are the total or partial viral genome integration within the cancer cell resulting in cell proliferation and migration, apoptosis inhibition, genomic instability and inhibition of DNA damage response. HBV and HCV may cause hepatocellular carcinoma (HCC) through chronic inflammation, which lead to the production of chemokines, cytokines and prostaglandins, reactive oxidative species and angiogenesis promotion. However, direct oncogenic mechanisms have also been demonstrated for both HBV and HCV in several studies.[4–9] Finally, HIV-1 exerts its oncogenic effect mostly through suppression of the host immune response, which leads to increased replication of oncogenic viruses such as EBV and KSHV.

According to the IARC criteria, there is sufficient evidence between chronic HBV and HCV infection and HCC development, sufficient evidence between chronic HCV infection and the development of non-Hodgkin lymphoma (NHL) and a positive association between chronic HBV infection and NHL.[3]

In this review, we summarize the epidemiological and clinical evidence demonstrating the association between chronic HBV and HCV infection with haematological malignancies. The purported oncogenic mechanisms of both viruses are described, and the clinical impact of viral suppression and eradication on the oncohaematological disease are discussed. The importance of antiviral prophylaxis to prevent HBV reactivation in patients with recovered HBV infection during therapy with immunosuppressive agents for oncohaematological malignancy is largely documented and strongly recommended.