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

Objective : Mixed cryoglobulinemia (MC) is an important com- plication 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 ; Chi2 = 28.9%). Stratified analysis did not meaningfully change the results. The frequency of patients stop- ping 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 symp- tomatic 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 immuno- suppressive agents are under way in order to improve efficacy and safety of symptomatic HCV-MC. (Acta gastroenterol. belg., 2013, 76, 363-371).