Prior to the discovery of the hepatitis C virus (viral particles shown on the left), there was an entity termed “essential cryoglobulinemia”–that is, cryoglobulinemia without an obvious explanation. While this term is still used, the true “essential cryoglobulinemia” is pretty rare, some cases of “hepatitis C-negative” cryoglobulinemia turned out instead to be positive: the cryoprecipitate can sequester hepatitis C antibody from the serum, so if there is a high suspicion for hepatitis C in a patient with detectable cryoglobulins, it is worthwhile to look for serologic evidence of hepatitis in the cryoprecipitate itself.
Interestingly up to 50% of all patients with hepatitis C will show some evidence of circulating cryoglobulins. However, these antibodies only become clinically significant in about 5%. So the presence of renal failure in a patient with hepatitis C and positive cryoglobulins does not absolutely define the renal disease as being cryoglobulin-mediated; a renal biopsy is often needed to clarify the etiology.