HCV-related lymphoproliferative disorders in the direct-acting antivirals era: from mixed cryoglobulinemia to B-cell lymphoma.

Summary Hepatitis C virus (HCV) has been shown to induce many B-cell lymphoproliferative disorders. B lymphocytes are specialized in producing immunoglobulins, and within chronic HCV infection they can cause a range that goes from polyclonal hypergammaglobulinemia without clinical repercussions, passing by mixed cryoglobulinemic vasculitis and eventually reaching B-cell non-Hodgkin lymphoma. This spectrum is supported by substantial epidemiological, pathophysiological and therapeutic data. Many, although not all, pathogenic pathways leading from one extreme to another have been decrypted. Chronic viral antigen stimulation of B lymphocytes has a central role until the last steps towards overt malignancy. This has direct implications in treatment strategies, which always include the use of direct-acting antiviral agents sometimes associated with immunosuppressants. The role of direct-acting antiviral agents has been well established in patients with cryoglobulinemia vasculitis. Its positive impact on B cell non-Hodgkin lymphoma needs to be confirmed in larger studies with longer follow-up.