Longterm efficacy of interferon-alpha for extrahepatic disease associated with hepatitis C virus infection.

Objective. To investigate longterm responsiveness to interferon-alpha (IFN-alpha) of patients with extrahepatic manifestations of hepatitis C virus (HCV) in a nonendemic area. Methods. We prospectively evaluated 11 patients with extrahepatic manifestations of HCV infection, including 10 with Type II cryoglobulins, treated with IFN-alpha -9 had cutaneous vasculitis, 6 arthralgias. 7 neuropathy, and 4 glomerulonephritis. Liver biopsies were performed on all patients. although 6/11 had normal liver function tests. All received 3 M units IFN-alpha tiw, with total length of treatment ranging from 3 mo to 5 yrs. Periodic assessments were made of clinical activity, biochemical variables, cryoglobulin quantitation, and HCV copy number. Results. Three patients were withdrawn because of toxicity. Three were nonresponders at 6, 16, and 17 mo of therapy, based on persistence of HCV RNA in blood. cryoprecipitates, and peripheral blood mononuclear cells. One patient was a partial responder at 3 yrs, with 2 major flares of cutaneous vasculitis occurring on separate attempts to withdraw IFN-alpha. Three patients (27.2%) were complete responders based on resolution of symptoms (purpura, neuropathy) and disappearance of cryoprecipitates and HCV RNA. but only one successfully tapered IFN-alpha after 3 yrs of treatment. with sustained resolution at followup 15 mo later. Conclusion. IFN-alpha is safely tolerated for prolonged periods in patients with extrahepatic HCV infection, and is particularly effective for treatment of cutaneous vasculitis. Careful monitoring is needed for evolution of liver pathology to cirrhosis, or for progression of renal or neurologic disease.