Myths, misconceptions and mixed cryoglobulinemia associated with HCV infection

The delineation of the association of HCV infection with mixed cryoglobulinemia has provided new insight into the etiology and pathogenesis of this extrahepatic manifestation of the infection. Yet very little evidence has been obtained thus far on the specific roles of virus in production of the monoclonal rheumatoid factors responsible for classic type II cryoglobulins and the associated clinical manifestations. The problematic areas of investigation that have in some instances generated misconceptions due to lack of data are reviewed. These include the prevalence and heterogeneity of mixed cryoglobulins; clinical manifestations such as liver cirrhosis, membranoproliferative glomerulonephritis, autoimmunity, progression of cryoglobulinemia from type III to type II, development of B cell malignancies; determination of lineages based on immunoglobulin gene utilization; and the anti-viral treatment of patients with mixed cryoglobulinemia.