Hepatitis C virus infection and B-cell non-Hodgkin's lymphomas: more than a simple association.

Several studies have reported that the prevalence of the hepatitis C virus (HCV) infection is significantly overrepresented in patients affected by non-Hodgkin's lymphoma (NHL), thus suggesting that besides the well-established link with essential mixed cryoglobulinemia, a possible role for HCV is determining the development of at least some types of B-cell NHL. Such an association, however, seems to be limited to geographic areas where the presence of HCV is more relevant or endemic. According to a multistep pathogenetic model based on a large series of clinical, immunological, histological, and molecular evidences, an HCV antigen-driven polyclonal B-cell lymphoproliferation could be the initial phase of a process leading, in a variable time, into a true clonal disease. Particular genetic and environmental backgrounds could play a role in the development of a malignant phenotype, while specific HCV genotypes do not seem to be relevant in this setting. Hepatitis C virus correlated with NHL often shows some distinctive clinicopathological features, such as older age, liver damage, presence of monoclonal gammopathy (often with no clinically relevant cryoglobulinemic and/or rheumatoid activity), increased rate of autoimmune disorders, extranodal localizations, and restricted histological subtypes. Overall, the clinical outcome of HCV-positive NHL does not seem to be different from that of NHL patients without HCV infection. However, the evidence of a significant hepatic injury may predict a worse prognosis in these subjects.