Treatment of refractory, symptomatic, hepatitis C virus related mixed cryoglobulinemia with ribavirin and interferon-alpha.

Objective: To assess the benefit of interferon-alpha/ribavirin combination therapy in hepatitis C virus (HCV) infected patients with symptomatic mixed cryoglobulinemia (MC) who failed to respond to treatment with interferon-alpha (IFN-alpha).
Methods: Nine patients (mean age 57 +/- 14 yrs) with type II symptomatic MC who failed to respond to IFN-alpha monotherapy were re-treated with combination treatment of IFN-alpha 3 times weekly and ribavirin 15 mg/kg daily for 6 months. Five of 9 patients had previously received additional treatment during IFN-alpha monotherapy. Clinical and laboratory evaluations (including cryocrit level) were performed weekly for the first month and monthly thereafter.
Results: Baseline mean alanine aminotransferase (ALT) and cryocrit levels were 119 +/- 97 IU/l and 7.9% +/- 10%, respectively. All patients were HCV-RNA positive and 5 had cirrhosis. At the end of therapy, mean ALT level was 84 +/- 79 IU/l (p = 0.02), while normal ALT levels were observed in 4 of 9 patients (44%). However, complete virological response was achieved in only 2 patients (22%). Cryoglobulin became undetectable within 6 weeks of therapy in 7 patients (78%) and decreased significantly in 2 others (p = 0.008). A substantial improvement in MC related symptoms (arthralgia/arthritis, proteinuria, skin vasculitis) was achieved in all patients within 10 weeks of combination therapy, although polyneuropathy related symptoms were relatively resistant to treatment.
Conclusion: Symptomatic, refractory HCV related MC should be considered as an indication for combination therapy with IFN-alpha and ribavirin. Improvement in MC related symptoms can be achieved even without complete biochemical or virological response.