Interferon mono-therapy for symptomatic HCV-associated mixed cryoglobulinemia : meta-analysis of clinical studies

Objective : Mixed cryoglobulinemia (MC) is an important complication of hepatitis C virus (HCV) infection. Antiviral therapy is now an important approach for symptomatic HCV-MC; some-information exists on IFN mono-therapy for symptomatic HCV-MC in the non-transplant setting, but its efficacy is still unclear. Methods : We evaluated efficacy and safety of mono-therapy with standard or pegylated interferon (IFN) for symptomatic HCV-associated MC in non-immunosuppressed individuals by performing a systematic review of the literature with a meta-analysis of clinical studies. We used the random-effects model of DerSimonian and Laird with heterogeneity and sensitivity analyses. The primary outcome was sustained viral response (SVR, as a-measure of efficacy), and the secondary outcome was the drop-out rate due to side-effects (as a measure of tolerability). Results : We identified eleven clinical studies (n = 235 unique-patients); the rate of baseline kidney involvement ranged between 11% and 74%. The summary estimate of frequency of sustained viral response was 0.15 with a 95% Confidence Interval (CI) of 0.08; 0.22 (random-effects model). Significant heterogeneity-occurred (P = 0.001; Chi(2) = 28.9%). Stratified analysis did not meaningfully change the results. The frequency of patients stopping antiviral agents was 3.4%; most patients experienced minor side effects which did not require interruption of therapy. Baseline cirrhosis (P < 0.04), kidney involvement (P < 0.07), and arthralgias (P < 0.04) showed negative impact on viral response. We found an excellent relationship between viral and clinical response [weighted K = 0.72 (95% CI, 0.54; 0.89)], by an evaluation at individual level on a subset of reports (n = 65 unique patients). Conclusions : This meta-analysis of clinical studies shows that antiviral therapy with standard or pegylated IFN alone for symptomatic MC associated with HCV gives satisfactory response in a minority of patients only. Clinical trials based on combination therapy (pegylated interferon plus ribavirin) or novel immunosuppressive agents are under way in order to improve efficacy and safety of symptomatic HCV-MC.