Relationship between cryoglobulinemia-associated nephritis and HCV infection

The pathogenetic mechanisms in hepatitis C virus (HCV)-related cryoglobulinemia are sustained by the chronic lymphocyte stimulation of HCV infection, and include the synthesis of IgM rheumatoid factor and tissue deposition of immunocomplexes, characterized by abnormal kinetics and an underlying lymphoproliferative disorder. Based on postulated pathogenetic mechanisms, therapeutic strategies include antiviral, immunosuppressive and immunomodulatory treatments. Combined interferon and ribavirin has shown a better response rate than interferon alone. Pegylated interferons are currently recommended in association with ribavirin. Advances in tolerance might be achieved by tailoring doses and treatment duration according to genotype and individual factors. Conventional immunosuppressive therapy has been widely used in patients with progressive renal involvement or relapsing disease. Rituximab is a promising alternative treatment option for severe cryoglobulinemic vasculitis and nephritis. Although the optimal treatment strategy in HCV-related cryoglobulinemia has not been determined yet, an algorithm based on the clinical severity of disease could be proposed, in which rituximab might be a first-line option in severe cases.