Background. Essential mixed cryoglobulinemia is frequently associated with hepatitis C virus (HCV) infection. A beneficial effect of interferon alfa therapy has been reported, but we do not know whether the antiviral activity of the drug affects the clinical and biochemical manifestations of disease. Methods. In a prospective randomized, controlled trial, we studied 53 patients with HCV-associated type I1 cryoglobulinemia. A group of 27 patients received recombinant interferon alfa-2a thrice weekly at a dose of 1.5 million units for a week and then 3 million units thrice weekly for the following 23 weeks. The 26 control patients did not receive anything apart from previously prescribed treatments. All patients were then followed for an additional 24 to 28 weeks. Results. Interferon was usually well tolerated, but it was permanently discontinued in two patients because of atrial fibrillation and depression. Two of the 26 patients in the control group were lost to follow-up. After the treatment period, serum HCV RNA was undetectable in 15 of the remaining 25 patients who received interferon alfa-2a, but in none of the controls. In comparison with the control group, the 15 patients with undetectable levels of HCV RNA in serum had significant improvement in cutaneous vasculitis (P = 0.04) and significant decreases in serum levels of anti-HCV-antibody activity (P = 0.007), cryoglobulins (P = 0.002), IgM (P = 0.002), rheumatoid factor (P = 0.001), and creatinine (P = 0.006).
After treatment with interferon alfa-2a was discontinued, viremia and cryoglobulinemia recurred in all 15 HCV RNA-negative patients. On resumption of treatment, three of four patients had virologic, clinical, and biochemical response. Conclusions. The therapeutic efficacy of interferon alfa-2a in HCV-associated cryoglobulinemia is closely related to its antiviral activity, thus supporting the idea that HCV infection may be a cause of this disease. (N Engl J Med 1994;330751-6.