Hepatitis C virus infection in patients with essential mixed cryoglobulinemia

Ann Intern Med. 1992 Oct 1;117(7):573-7. doi: 10.7326/0003-4819-117-7-573.


Objective: To study the association between hepatitis C virus (HCV) infection and essential mixed cryoglobulinemia.

Setting: Wards and clinics of the Ospedali Riuniti di Bergamo and Ospedale di Treviglio e Caravaggio, Italy.

Patients: Fifty-one patients with essential mixed cryoglobulinemia associated with glomerulonephritis and 45 controls with noncryoglobulinemic glomerulopathies.

Measurements: Antibodies to hepatitis C virus (anti-HCV) in sera from patients with essential mixed cryoglobulinemia and from controls, using two enzyme-linked immunosorbent assays (c100 ELISA and c22/c200 ELISA) and a recombinant immunoblot assay (4-RIBA); cryoprecipitate anti-HCV before and after use of dithiothreitol, a substance able to destroy IgM antibodies with rheumatoid factor activity, in patients with essential mixed cryoglobulinemia; serum HCV RNA by polymerase chain reaction in patients with essential mixed cryoglobulinemia.

Results: In patients with essential mixed cryoglobulinemia, the c22/c200 ELISA detected anti-HCV in 98% of serum samples (95% CI, 90% to 100%), whereas the rate of reactivity remained at 2% (CI, 0% to 12%) in the control group (P less than 0.0001). These results were confirmed by the 4-RIBA in 66% of patients with essential mixed cryoglobulinemia. The study of cryoprecipitate by c100 ELISA showed anti-HCV in 41% (Cl, 28% to 56%) of patients. After dithiothreitol, the rate of reactivity increased to 94% (CI, 84% to 99%; P less than 0.0001 by the McNemar paired chi-square test), suggesting that the elimination of rheumatoid factor leads to unmasking of anti-HCV in cryoprecipitate. Polymerase chain reaction detected HCV RNA in 13 of 16 sera from patients with essential mixed cryoglobulinemia.

Conclusions: The extremely high prevalence of anti-HCV in serum and cryoprecipitate along with the frequently associated serum HCV RNA suggests a close relation between essential mixed cryoglobulinemia and chronic HCV infection.

MeSH terms

  • Base Sequence
  • Cryoglobulinemia / complications*
  • Cryoglobulinemia / microbiology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Hepacivirus / isolation & purification
  • Hepatitis Antibodies / blood
  • Hepatitis C / complications*
  • Hepatitis C / immunology
  • Humans
  • Immunoblotting
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • RNA, Viral / blood


  • Hepatitis Antibodies
  • RNA, Viral