Antiviral therapy of hepatitis C in chronic kidney diseases: meta-analysis of controlled clinical trials

Abstract

Hepatitis C virus (HCV) infection remains frequent in patients with chronic kidney disease and the detrimental role of HCV on survival is well-established in this population. Several authors have reported on efficacy and safety of antiviral therapy for hepatitis C in this polulation but there is no clear consensus on management. To evaluate efficacy and safety of antiviral therapy for hepatitis C in patients with chronic kidney disease, we performed a systematic review of the published medical literature and completed a meta-analysis of controlled clinical trials. The primary outcome was sustained virological response (as a measure of efficacy); the secondary outcome was drop-out rate (as a measure of tolerability). We used the random effects model of Der Simonian and Laird, with heterogeneity and sensitivity analyses. We identified 13 studies including 539 unique patients; 10 (76.9%) concerned patients on maintenance dialysis. Only prospective, controlled clinical trials were included. Pooling of study results showed a significant increase of viral response in study (patients treated with antiviral therapy) than control patients (patients who did not receive therapy), the pooled odds ratio (OR) of failure to obtain a sustained viral response was 0.081 [95% confidence intervals (CI), 0.029-0.230], P = 0.0001. The pooled OR of drop-out rate was significantly increased in study vs control patients, OR = 0.389 (95% CI, 0.155-0.957), P = 0.04. The studies were heterogeneous with regard to viral response and drop-out rate. In the subset of clinical trials (n = 6) involving only dialysis patients receiving interferon (IFN) monotherapy for chronic HCV, there was a significant difference in the risk of failure to obtain a sustained viral response (study vs control patients), OR = 0.054 (95% CI, 0.019; 0.150), P = 0.0001 (random-effects model). No significant (NS) heterogeneity was found (Q = 14.604, P = 1.0). No difference in the drop-out rate between study and control patients was shown, OR = 0.920 (95% CI, 0.367; 2.311), NS. This result being homogeneous (Q = 3.639, P = 0.388). Our meta-analysis showed that the viral response was greater in patients with chronic kidney disease who received antiviral therapy than controls. No difference in the drop-out rate between study and control patients occurred in the subgroup of dialysis patients on IFN monotherapy. These results support IFN-based therapy for hepatitis C in patients on maintenance dialysis.