Cryoglobulins and cryoglobulins secondary to hepatitis C virus infection

Cryoglobulins are a mixture of immunoglobulins and complement components that precipitate at temperature lower than 37 C. Cryoglobulinaemia (CG) means the presence of cryoglobulins in a patient's serum, but it is also referring to an inflammatory syndrome that generally involves small to medium vessel vasculitis because of cryoglobulin containing immune complexes. Prior to the identification of hepatitis C virus (HCV) in 1989, CG was largely termed 'essential' in patients who do not have associated lymphoproliferative disease or autoimmune disease. It is now recognized that up to 90% of patients with clinically evident CG have chronic HCV infection. The role of HCV in pathogenesis of CG and the treatment options are discussed in this chapter. Because HCV has a clear biological role in pathogenesis of CG in most patients, one must consider eradicating HCV with antiviral therapy. Interferon-based treatment reduces viral replication rate, inhibits lymphocyte proliferation and immunoglobulin synthesis, and improves immune complex clearance by enhancing macrophage activity. In terms of clinical response, the effectiveness of interferon-alpha is comparable to that observed in the management of HCV without CG. The latest development against the abnormal B-cell clone driven by HCV is the anti-CD 20 monoclonal antibody, rituximab. This agent has previously been shown activity in B-cell lymphomas and autoimmune disorders. However, because rituximab decreases anti-HCV antibody titers and increases viremia, long term effect of rituximab on the liver disease is not known.