Hepatitis C-associated B-cell non-Hodgkin lymphomas. Epidemiology, molecular signature and clinical management

• Published in: Journal of hepatology Vol. 59; no. 1; pp. 169 - 177
• Main Authors: Peveling-Oberhag, Jan, Arcaini, Luca, Hansmann, Martin-Leo, Zeuzem, Stefan
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-07-2013
• Subjects: Antineoplastic Agents - therapeutic use; Antiviral Agents - therapeutic use; Antiviral therapy; B-cell; B-Lymphocytes - immunology; B-Lymphocytes - virology; Gastroenterology and Hepatology; Hepacivirus - immunology; Hepacivirus - pathogenicity; Hepatitis C; Hepatitis C Antigens; Hepatitis C, Chronic - complications; Hepatitis C, Chronic - drug therapy; Hepatitis C, Chronic - epidemiology; Humans; Lymphoma; Lymphoma, B-Cell - drug therapy; Lymphoma, B-Cell - epidemiology; Lymphoma, B-Cell - etiology; Models, Biological; Non-Hodgkin lymphoma; Risk Factors; Non-Hodgkin lymphoma; Antiviral therapy; Hepatitis C; B-cell; Lymphoma
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/j.jhep.2013.03.018

Summary There is ample epidemiologic evidence for an association of chronic hepatitis C virus (HCV) infection with B-cell non-Hodgkin lymphoma (B-NHL). B-NHL subtypes most frequently associated with HCV are marginal zone lymphoma and diffuse large B-cell lymphoma. The most convincing evidence for a causal relationship between HCV infection and lymphoma development is the observation of B-NHL regression after HCV eradication by antiviral therapy (AVT). In fact, for indolent HCV-associated B-NHL, first-line AVT instead of standard immune-chemotherapy might be considered. Molecular mechanisms of HCV-NHL development are still poorly understood. Three general theories have emerged to understand the HCV-induced lymphomagenesis: (1) continuous external stimulation of lymphocyte receptors by viral antigens and consecutive proliferation; (2) HCV replication in B cells with oncogenic effect mediated by intracellular viral proteins; (3) permanent B-cell damage, e.g., mutation of tumor suppressor genes, caused by a transiently intracellular virus (“hit and run” theory). This review systematically summarizes the data on epidemiology, interventional studies, and molecular mechanisms of HCV-associated B-NHL.