BACKGROUND AND RATIONALE:The role of hepatitis C virus (HCV) as an independent risk factor for death in dialysis population is unclear. DESIGN:A systematic review of the published medical literature was performed to evaluate the impact of positive anti-HCV serologic status on all-cause and disease-specific mortality in patients on regular dialysis. The risk of all-cause, cardiovascular and liver disease-related mortality was regarded as the most reliable outcome end-point. Study-specific relative risks were weighted by the inverse of their variance to obtain fixed- and random-effects pooled estimates for mortality with HCV across the published studies. RESULTS:Twenty-three observational studies (n = 574,081 patients on long-term dialysis) were identified. Pooling of study results demonstrated that HCV positive status was an independent and significant risk factor for death in patients on maintenance dialysis. The summary estimate for adjusted death risk (all-cause mortality) with HCV was 1.26 (95% CI: 1.18; 1.34) (P < 0.0001). Between-study heterogeneity was found (Q value 52.8, P = 0.001). The overall estimate for adjusted death risk (liver disease-related mortality) was 5.05 (95% CI: 2.53; 10.0) (P < 0.0001); heterogeneity statistics, Q value 8.2, P = 0.04. The overall estimate for adjusted death risk (cardiovascular mortality) was 1.18 (95% CI: 1.085; 1.29) (P < 0.0001) (no heterogeneity). Meta-regression showed that the effect of HCV on all-cause mortality was more evident in those studies provided with a greater size (P = 0.0001), a higher prevalence of diabetics (P = 0.0005) and HCV-infected individuals (P = 0.001). CONCLUSIONS:An association between HCV positive serologic status and increased risk of either liver or cardiovascular disease-related mortality exists among dialysis patients.

Background

Controversy persists about the role of hepatitis C as a risk factor for developing kidney disease in the general population. Some authors have evaluated the effect of antiviral therapy for HCV on the risk of kidney disease.

Study aims and design

A systematic review of the published medical literature was performed to assess whether antiviral therapy for HCV has an independent impact on kidney survival in the adult general population. A random effects model was used to generate an overall estimate of the risk of kidney disease after anti-HCV therapy across the published studies. Meta-regression and stratified analysis were also carried out.

Results

Fifteen studies were eligible (n=356, 285 patients) and separate meta-analyses were conducted according to the outcome. Pooling studies based on viral responses (n=7; 34,763 individual patients) demonstrated a relationship between sustained viral response and lower frequency of kidney disease; the overall estimate for adjusted risk of kidney disease was 2.50 (95% CI, 1.41; 4.41) (p=0.0016) and between-study heterogeneity was found (p-value by Q test=0.004). Aggregation of studies comparing treated vs untreated cohorts (n=8, n=333,312 patients) revealed an association between anti-HCV therapy and lower risk of kidney disease. The overall estimate for adjusted risk of kidney disease across the eight studies was 0.39 (95% CI, 0.25; 0.612) (p=0.0001). Meta-regression showed that the effectiveness of antiviral therapy in reducing the frequency of kidney disease diminishes as cirrhosis (p=0.02) and HBV infection (p=0.0001) increase among HCV-infected individuals.

Conclusions

Antiviral therapy for HCV lowers the risk of kidney disease among HCV-infected individuals. Studies to understand the mechanisms underlying this association are ongoing.