Interferon therapy for HCV-associated glomerulonephritis : meta-analysis of controlled trials

Background: A relationship between hepatitis C virus (HCV) infection and chronic glomerulonephritis (GN) has been asserted on the grounds of epidemiological and experimental data. Although this suggests a role for an antiviral approach to HCV-associated GN instead of the more conventional immunosuppressive (or supportive) therapy, the optimal management of HCV-related glomerulonephritis remains controversial. Objective: To compare antiviral with immunosuppressive therapy for HCV-associated GN. Design: Meta-analysis of controlled clinical trials (CCTs) of the two treatments (antiviral versus immunosuppressive) of HCV-associated GN. Methods: We used the fixed or random effects model of DerSimonian and Laird, with heterogeneity and sensitivity analyses. The rate of proteinuria and serum creatinine decrease after therapy for HCV-associated GN were regarded as the most reliable outcome end-points. Results: We identified six studies involving 145 unique patients with HCV-associated GN. Pooling of study results demonstrated that proteinuria decreased more commonly after IFN than corticosteroid therapy (OR 1.92 (95% CI, 0.39; 9.57), NS), P-test for heterogeneity, 0.06 (I2=52.9%). In a sensitivity analysis including only CCTs using standard IFN-doses, OR was 3.86 (95% CI, 1.44; 10.33, (P=0.007)), P-test for heterogeneity, 0.18 (I2=35.9%). No improvement of serum creatinine after IFN compared to immunosuppressive therapy was noted (OR, 0.59 (95% CI, 0.21; 1.65), NS), P-test for heterogeneity, 0.76 (I2=0%). Only three CCTs gave information on the rate of proteinuria decrease over follow-up (OR, 5.08 (95% CI, 0.69; 37.31), NS). A few major side effects were noted after IFN administration. Conclusions: Our meta-analysis indicates that standard IFN-doses were more effective than immunosuppressive therapy in lowering proteinuria of patients with HCV-related glomerulonephritis. However, no significant improvement in serum creatinine was seen by IFN or steroid therapy across the studies. Also, information on proteinuria recurrence after the completion of antiviral therapy was not sufficient. Prospective, randomized trials based on combined antiviral therapy (pegylated IFN plus ribavirin) with adequate dose and follow-up are required to assess the efficacy and safety of antiviral treatment of HCV-associated glomerulonephritis.