HEPATITIS-C VIRUS-INFECTION IN SUBSETS OF NEOPLASTIC LYMPHOPROLIFERATIONS NOT ASSOCIATED WITH CRYOGLOBULINEMIA

Hepatitis C virus (HCV) is both hepatotropic and lymphotropic and a de ar-cut association has been proposed between HCV infection and mixed c ryoglobulinemia (MC), a benign lymphoproliferative disorder, which som etimes evolves into a frank malignant B cell non-Hodgkin's lymphoma (B -NHL). Moreover, the presence of antibodies to HCV, as well as of HCV- specific genomes has been reported in the sera of over 37% patients wi th B-NHL, not associated with MC. Thus, we decided to perform both a s erologic and a molecular study to give insights into a possible relati onship between HCV infection and neoplastic lymphoproliferations. We u sed ELISA and RIBA tests to show that anti-HCV antibodies were present in the serum of 29 out of 69 unselected B-NHL patients (42%), while s eropositivity in a healthy population was about 1%. The prevalence of anti-HCV antibodies was low in definite subsets of B lymphoid disorder s, including multiple myeloma, Waldenstrom's macroglobulinemia and mon oclonal gammopathies of undetermined significance. Then, using reverse transcriptase polymerase chain reaction, we detected HCV sequences di rectly in the pathologic lymph node biopsies in 13 out of 34 B-NHL cas es, and in particular in six out of eight low-grade lymphomas of MALT type and in five out of eight centroblastic-centrocytic follicular lym phomas. In contrast, the peripheral blood samples from 10 B cell chron ic lymphocytic leukemia patients resulted negative for the presence of HCV genomes. Similarly, viral sequences were absent in 10 T cell NHL, while only one out of the 14 Hodgkin's disease cases tested resulted positive. Finally, we used a PCR-based assay to characterize the genot ypes (I-IV) present in the positive lymphomatous tissues. The presence of both serologic and molecular markers of HCV infection in a high pe rcentage of certain types of B-NHL, not associated with cryoglobulinem ia, and its absence from other lymphoproliferative diseases extends th e spectrum of HCV-associated lymphoproliferations arguing in favor of some role of this viral infection in the pathogenesis of the malignant proliferation of definite B lymphoid populations.