Antiviral therapy in HCV-positive non-hodgkin's lymphoma: Pathogenetic implications

Abstract

Growing evidence indicates an association between chronic HCV infection, with or without mixed cryoglobulinemia, and a subset of B-cell non-Hodgkin's lymphoma (B-NHL), although geographical heterogeneity has been described in its prevalence. In addition to persistent antigenic stimulation by HCV that results in the maintenance of clonal B-cell proliferation, genetic and environmental factors have been suggested to play a role in the progression to frank lymphoid malignancy. In a retrospective cohort study carried out in the USA, HCV infection was determined to confer a 20-30% increased risk of developing B-NHL as compared with uninfected patients. In Italy, approximately 5% of all B-NHLs are believed to be causally related to HCV. On the basis of these considerations, an effective antiviral therapy and the ensuing sustained virological response (SVR) would be expected to induce the regression of B-NHL. This was first shown in 2002 in patients with splenic lymphoma with villous lymphocytes. A systematic review of subsequent studies reported that 75% of HCV-infected patients with B-NHL treated with pegylated interferon-α (pIFN-α) plus ribavirin (RBV) achieved a complete hematological response (CHR), whereas no such response was obtained in matched HCV-uninfected B-NHL patients. Our own experience refers to a retrospective analysis: 10 out of 13 (77%) HCV-positive patients with B-NHL achieved a SVR and 8 of them (61%) were considered to be in CHR following 1 year of combined pIFN-α plus RBV therapy. By contrast, CHR was observed in a lower percentage (33%) and for a shorter duration among 15 additional HCV-positive patients with B-NHL who received the same antiviral therapy but had been treated with one or more chemotherapeutic regimens. Further studies are required to gain a deeper insight of the relationships between HCV infection and lymphomagenesis.