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

Objective. To assess the benefit of interferon-α/ribavirin combination therapy in hepatitis C virus (HCV) infected patients with symptomatic mixed cryoglobulinemia (MC) who failed to respond to treatment with interferon-a (IFN-α). Methods. Nine patients (mean age 57 ± 14 yrs) with type II symptomatic MC who failed to respond to IFN-a monotherapy were re-treated with combination treatment of IFN-a 3 times weekly and ribavirin 15 mg/kg daily for 6 months. Five of 9 patients had previously received additional treatment during IFN-a 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 poly neuropathy related symptoms were relatively resistant to treatment. Conclusion. Symptomatic, refractory HCV related MC should be considered as an indication for combination therapy with IFN-a and ribavirin. Improvement in MC related symptoms can be achieved even without complete biochemical or virological response.