Mixed cryoglobulinemia and hepatitis C virus infection

The striking association between hepatitis C virus (HCV) infection and mixed cryoglobulinemia (MC) has conducted to the hypothesis that HCV plays a major role in the production of MC. MC is a systemic vasculitis characterized by the presence in the serum of cryoprecipitable immunoglobulins (Ig), with rheumatoid factor (RF) activity. HCV which is both a hepatotropic and lymphotropic virus, has been proposed as a causative agent of MC, and is responsible for clinic manifestations such as glomerulonephritis, vasculitis, neuropathy. Because MC evolves frequently into B-cell non-Hodgkin lymphoma (NHL), chronic HCV infection has been proposed as an aetiologic factor in B-cell lymphoma. Several controlled trials have demonstrated that combined therapy with interferon and ribavirin is beneficial in chronic hepatitis C with and without MC. Several studies have also suggested that interferon alpha or association of corticosteroids and or ribavirin to the interferon alpha regimen can attenuate the clinical manifestations of MC and considerably reduce CG production. Different situations can be encountered which may modify treatment strategies: patients may be asymptomatic carriers of cryoglobulins but may have chronic hepatitis according to usual criteria, in some cases, cryoglobulinemic patients have no active liver disease, with normal alanine amino transferase and mild liver lesions at liver biopsy, but severe manifestations of MC, in other patients, active liver disease and MC related symptoms are both present.