Hepatitis C and Lymphoproliferative Disorders: From Mixed Cryoglobulinemia to Non-Hodgkin's Lymphoma

Abstract

Hepatitis C virus is associated with both mixed cryoglobulinemia and non-Hodgkin's lymphoma, particularly B-cell non-Hodgkin's Lymphoma. Although there are geographic discrepancies in the incidence and prevalence of hepatitis C virus-related lymphomas, large epidemiologic studies and meta-analyses confirm this relationship in both patients with and without mixed cryoglobulinemia. Other factors such as gene translocation, somatic hypermutation and direct infection may also play a role in the malignant transformation of B-cells. Recent advances in our understanding between the complex relationship between hepatitis C virus and its interactions with cell proteins on B-cell surface membranes has led to proposed mechanisms on how hepatitis C virus leads to chronic antigenic stimulation resulting in lymphoproliferation. Hepatitis C virus is more weakly associated with T-cell lymphomas, Waldenstrom's macroglobulinemia and other monoclonal gammopathies. Remission of mixed cryoglobulinemia is strongly associated with reduction of hepatitis C virus viral load and recurrence of disease corresponds with viral relapse. Similarly, some studies have shown complete remissions of low grade lymphomas with sustained viral response after antiviral therapy for hepatitis C virus. Further studies are needed to more clearly understand the pathogenesis and management of hepatitis C virus-related lymphoproliferative disorders.