Hepatitis C computer virus (HCV) infection leads to chronic liver disease but also to extra-hepatic manifestations. unfortunately the results were disappointing. In 15 patients who had a complete clearance of HCV RNA after α-IFN therapy an improvement in renal function was observed (37). However there was no effect on proteinuria and all patients relapsed after α-IFN therapy was stopped. Later in a prospective uncontrolled study 14 patients experiencing an HCV-related glomerulonephritis were treated with α-IFN for 6 to 12 months (9). Overall proteinuria significantly decreased while renal function remained stable. In 11 patients sera were tested for HCV RNA while on this therapy. Patients who became cleared of HCV RNA (n=6) had a better outcome compared to those who remained HCV RNA positive (n=5). However virological and renal relapses were observed after completing the therapy. In this study in five patients the use of oral prednisone in addition to α-IFN had no effect on renal function. In contrast steroid pulses had a beneficial effect in two patients. Finally the use of cytotoxic brokers with or without plasma exchange was associated with a high rate of death and a flare-up in HCV viremia (9). Flavopiridol HCl During the last few years a combined therapy of α-IFN especially pegylated IFN with ribavirin has become the gold standard of HCV treatment because it has been found to be more effective than α-IFN alone (See “Treatment of chronic hepatitis C computer virus infection: Recommendations for adults-I”). This has prompted physicians to treat HCV-related glomerulonephritis with this combination. However published case reports and uncontrolled studies have only included small numbers of patients so far. In a prospective uncontrolled study 20 patients presenting with MPGN (n=17) membranous glomerulonephritis (n=2) and mesangioproliferative glomerulonephritis (n=1) were treated with α-IFN and either with or without ribavirin (38). All patients were given α-IFN 3 MU three times weekly. In cases of persistent HCV RNA at 3 months ribavirin was added at the daily dose of 15 mg/kg: treatment was continued for 12 months. Four out of the 20 patients became HCV RNA unfavorable within the first 3 months MIF and consequently did not receive ribavirin therapy. Only one out of the 16 remaining patients who additionally received ribavirin became cleared of HCV RNA within the serum. Seven patients underwent a ribavirin dose reduction due to adverse events mainly hemolytic anemia. Overall both Flavopiridol HCl HCV RNA concentration and proteinuria decreased significantly. Serum-albumin level as well as both C3 and C4 complement-component levels increased significantly. Renal function remained stable. In this study no data are provided regarding the outcome of renal disease after cessation of anti-HCV therapy. In order to reduce ribavirin-induced Flavopiridol HCl hemolytic anemia some authors have developed a high-performance liquid chromatography method to monitor the plasma ribavirin level and have reported on their first treatment with concentration-controlled ribavirin plus α-IFN therapy in HCV-related glomerular disease (39). The intended trough ribavirin plasma concentration was 10 to 15 mmol/L. Four patients received standard α-IFN two received pegylated α-IFN and ribavirin and Flavopiridol HCl one patient received ribavirin monotherapy because of poor tolerance to α-IFN. Five of the patients had a sustained virological response 6 to 32 months after antiviral therapy was stopped. One patient relapsed 3 months after completing therapy whereas one patient who was receiving ribavirin monotherapy did not have a virological response. Serum-albumin level normalized in all patients and proteinuria decreased in all patients. Glomerular filtration rate improved in three patients and remained stable in four other patients. Despite monitoring ribavirin plasma concentration the main side-effect observed was ribavirin-induced hemolytic anemia which required a ribavirin-dose reduction low-dose iron and systematic erythropoietin support. An improvement in renal histology has been also reported in a small number of patients (40). More recently 18 patients who had HCV-related cryoglobulinemic MPGN were treated with a combined therapy of standard or pegylated interferon and ribavirin (41)..