Epidemiologic studies have shown hepatitis C virus (HCV) infection in a statistically significant proportion of de novo B-cell non-Hodgkin lymphomas that are not complicating the course of type II mixed cryoglobulinemia [1-3].

To study the influence of specific HCV genotypes on the pathogenesis of B-cell non-Hodgkin lymphoma, we analyzed 97 HCV-positive (anti-HCV antibody-positive and HCV RNA-positive) patients, including 35 patients with B-cell non-Hodgkin lymphoma that was not complicating the course of type II mixed cryoglobulinemia, 27 patients undergoing long-term hemodialysis, and 35 patients with chronic liver disease. The HCV genotype was determined by using a genotype-specific primer polymerase chain reaction method [4]. Results are summarized in the (Table 1). The prevalence of hepatitis C virus genotype 1b/II was unexpectedly lower in patients with B-cell non-Hodgkin lymphoma (25.7%) than in patients undergoing long-term hemodialysis (66.7%; P = 0.0013) and those with chronic liver disease (62.8%; P = 0.001). Conversely, the prevalence of genotypes 2a/III and 2b/IV was higher in patients with B-cell non-Hodgkin lymphoma (42.8%) than in the hemodialysis group (14.8%; P = 0.01) and chronic liver disease group (14.2%; P = 0.008).

The possible clinical relevance of the presence of different genotypes, in terms of prognosis or therapeutic response, in HCV-associated diseases has now emerged [5]. A high prevalence of genotype 2a/III in Italian patients who had cryoglobulinemia without associated liver disease but with circulating autoantibodies was recently reported; this finding suggests that this variant may have a pathogenetic role in autoimmune-lymphoproliferative disorders [4]. The different genotype distribution in our series of de novo B-cell non-Hodgkin lymphoma in comparison with patients undergoing hemodialysis and patients with chronic liver disease further supports the hypothesis that different HCV variants might be related to greater lymphotropism. Moreover, our observation indicates that HCV-related factors, namely viral genotypes, may play a role in the malignant proliferation of defined B-cell subsets, in addition to unknown host-related factors.