Extra-hepatic manifestations of HCV infection: From pathogenesis to clinical management

Hepatitis C virus is associated with chronic liverdisease as well as with lymphoproliferative disorderssuch as mixed cryoglobulinemia and, likely, nonHodgkin’slymphomas. The association between HepatitisC virus infection and B-cell lymphoma shows a strongregional variation and the intimate pathogenetic involvedin Hepatitis C virus-related lymphomas remains considerably unknown. HepatitisC virus may exert its oncogenic potentials via an indirect mechanism ordirectly utilise other pathways. It is reasonable to assume that several differentpathogenetic mechanisms operate in the wide spectrum of Hepatitis C virusrelatedlymphoproliferative disorders, which include low and high-gradelymphomas, preceded by long standing or absence of mixed cryoglobulinemia.In this review, the etiopathogenetic role of Hepatitis C virus in lymphoproliferativediseases is discussed on the basis of epidemiological, immunophenotyping, andmolecular considerations. A pathogenetic clue of potential relevance for thedefinition of innovative therapeutic approaches for HCV-related lymphoproliferationscame from the molecular characterization of the immunoglobulin genesexpressed by clonally expanded B cells, sustaining these disorders. In fact,several studies have consistently demonstrated that the immunoglobulinsexpressed by HCV-related B-cell lymphoproliferations share a very restricteduse of variable region gene segments, particularly of the light chain. Thesefindings provide the rational background apply these clonotypic immunoglobulinsfor vaccination purposes in this clinical setting.