Hepatitis C virus, mixed cryoglobulinemia and non-Hodgkin’s lymphoma

There is increasing evidence from recent studies that a large number of diseases are related to infections. In the field of haematology, many malignant disorders are now related to some infectious agents, such as Epstein-Barr virus (EBV) in Burkitt's lymphoma, human T lymphocyte virus I (HTLV-I) in T-cell leukaemia-lymphoma, Helicobacter pylori in gastric B-cell lymphoma, human herpes virus (HHV-6, -7, -8) in Kaposi's sarcoma and Castelman's disease and, perhaps, parvovirus B19 in pure red cell aplasia. However, all these infectious agents are widespread in the general population, but only a very small fraction of infected patients develop the neoplastic disease, indicating the crucial role of some, at present unknown, underlying genetic factors. An association between HCV infection and B-cell lymphoma has been demonstrated in several geographical areas. Although controversy remains, a pathogenetic linkage between HCV and NHL is strongly suggested by molecular and epidemiological evidence. However, despite this evidence, the pathogenetic mechanisms underlying HCV-associated lymphomas are still unknown. HCV-related lymphomas could, therefore, represent an important model for analysing virus–induced lymphomas in humans. It has not been elucidated whether HCV exerts its oncogenic effect through an indirect mechanism or whether it uses other pathways directly. It can be said that in most cases the viral infection does not have a significant impact on either response to chemotherapy or survival of lymphoma patients. Chemotherapy is relatively safe and treatment regimes do not usually need to be interrupted. Since the treatment of HCV infection can lead to regression not only of chromosomal and molecular abnormalities, but even of clinically evident low-grade NHL118.119, new therapeutic strategies (pegylated interferons plus ribavirin), currently recognised as the gold standard for HCV antiviral therapy and able to eradicate HCV in a high percentage of treated subjects (from 60 to 90% of complete responders on the basis of HCV genotype: 1 vs. non-1) are likely to drastically reduce the number of HCV infected patients and, consequently, the number of HCVrelated NHL.