Response to interferon- therapy has been reported in patients with mixed cryoglobulinemia (MC) and membranoproliferative glomerulonephritis (MPGN) associated with hepatitis C virus (HCV) infection, but relapses are frequent [1]. We describe a patient with HCV-related type II MC and MPGN who responded to treatment with ribavirin [2].

A 49-year-old man with the nephrotic syndrome was referred to us for evaluation. For 8 years, he had been followed for hypertension, edema, hematuria, and proteinuria. Maintenance therapy included enalapril, clonidine, furosemide, and prednisone (10 mg daily). In 1993, HCV infection was diagnosed by the presence of antibody to HCV, determined by enzyme immunoassay, and detection of HCV RNA by polymerase chain reaction. The patients' serum alanine aminotransferase (ALT) levels were elevated, and examination of a liver biopsy specimen showed chronic active hepatitis. The patient was given oral ribavirin (600 mg daily for 2 months, then 1000 mg daily for 2 months, then 1200 mg daily for 2 months). After drug cessation, he was normotensive without edema, despite discontinuation of clonidine therapy and reduction in the prednisone dose (5 mg daily). His ALT level was normal, his serum albumin level had increased from 3.6 g/dL to 4.3 g/dL, and MC decreased from 0.47 to 0.14 mg/mL. No HCV RNA was detected in serum, and proteinuria had decreased from 1.1 g/d to 0.4 g/d by the end of treatment. Two months after cessation of ribavirin, the patient's ALT values returned to pretreatment levels, his serum albumin level decreased to 3.2 g/dL, MC increased to 0.35 mg/mL, and proteinuria increased to 3.1 g/d. Antihypertensive drugs were reintroduced, and the prednisone dose was increased.

Other researchers have established an association between HCV infection and MPGN [3]. It is unknown, however, whether MPGN occurs by deposition of immune complexes that contain HCV or by induction of autoantibodies to native renal antigens [3]. Quigg and colleagues [4] successfully used cyclophosphamide to treat a cryoglobulinemic patient who had MPGN and HCV infection. Despite an increase in HCV RNA levels, cryoglobulins were no longer detected. The authors suggested that HCV-related cryoglobulinemia was an autoimmune process rather than a direct effect of HCV.

Unlike interferon- or cyclophosphamide, ribavirin has only antiviral activity [2-4]. In our opinion, the observed improvement in the nephrotic syndrome associated with viral clearance suggests that HCV represents a necessary stimulus in the pathogenesis of both MC and MPGN.