Interferon-alpha in combination with ribavirin as initial treatment for hepatitis C virus-associated cryoglobulinemic membranoproliferative glomerulonephritis.

Mixed cryoglobulinemia (MC) and glomerulonephritis are the most important extrahepatic manifestations of chronic hepatitis C virus (HCV) infection. In HCV-infected patients with MC, renal involvement worsens the overall prognosis because of a high incidence of infection or cardiovascular disease. The relationship between MC and HCV infection has prompted the use of antiviral therapy. Two patients with chronic HCV infection, type-II MC and membranoproliferative glomerulonephritis (MPGN), presenting as nephrotic syndrome were treated with interferon (IFN)-alpha (3 MU 3 times per week) and ribavirin (15 mg/kg daily) for 6 months. Laboratory tests included measurement of anti-HCV antibodies, HCV RNA, and HCV genotyping, and characterization of circulating cryoglobulins. A pretreatment renal biopsy was performed, and the histopathologic lesions were scored according to the index of disease activity. Viremia and cryoglobulinemia were suppressed in both patients. However, a complete remission of proteinuria was observed in 1 patient only. The evaluation of the renal biopsy specimens revealed a mild MPGN (activity score: 5/24) in the patient with remission of proteinuria and a severe MPGN (activity score: 15/24) in the patient who maintained a nephrotic-range proteinuria. Although a fully satisfactory treatment is not yet available, we feel that a reasonable therapeutic strategy for HCV-infected patients with MC nephritis could be as follows: (1) antiviral treatment alone for patients with a low-grade kidney involvement, and (2) a short-term course of steroids and cytotoxic drugs followed by antiviral therapy for acute exacerbations and/or rapidly progressive GN.

[Cryoglobulinemia and hepatitis C virus infection]. / Crioglobulinemie e infezione da virus dell'epatite C.

The demonstration of the high prevalence of HCV infection (HCV) in patients with MC has changed the clinico-biologic scenario of MC, supporting its subdivision into two groups: MC HCV- and MC HCV+. The former, which is predominantly a polyclonal cryoglobulinemia, should be regarded as an epiphenomenon of the immune system activation in the course of a variety of chronic infections or autoimmune disorders; the latter, which is a oligo- or monoclonal cryoglobulinemia, referred in the past as "essential mixed cryoglobulinemia", might be expression of an indolent B cell proliferation stimulated by HCV in an antigen-driven mechanism. The association of HCV infection with MC may have a pathogenetic an therapeutic significance. There are a number of reports demonstrating the beneficial effects of alpha-interferon (alpha-IFN) in about a half of patients with chronic HCV and MC. However, after the end of alpha-IFN therapy a recurrence of viremia and cryoglobulinemia is frequently observed and less than 25% of treated patients achieve long term remissions. To improve the sustained response rate, prolonged courses of alpha-IFN monotherapy or a combination of alpha-IFN and ribavirin should be considered. New agents with specific antiviral activity against HCV will probably further improve therapeutic options.