Hepatitis C and Its Metabolic Complications in Kidney Disease

Evidence has been accumulated during the last decade showing that HCV infection plays an important activity at hepatic and extra-hepatic level. Chronic HCV is associated with a large spectrum of extra-hepatic manifestations including lympho-proliferative diseases and metabolic abnormalities (such as insulin resistance and fatty liver disease).

We have performed an extensive review of the medical literature regarding the increased risk of cardiovascular and kidney disease that has been observed in various groups of HCV-infected patients. The potential link between such increased risk and the metabolic consequences of chronic HCV infection has been explored.

According to a systematic review with a meta-analysis of longitudinal studies (n = 9 clinical observational studies; n = 1,947,034 unique patients), we found a strong relationship between positive anti-HCV serologic status and increased incidence of chronic kidney disease in the adult general population, the summary estimate for adjusted hazard ratio was 1.43 (95% confidence intervals, 1.23; 1.63, P = 0.0001) (random-effects model) in anti-HCV positive patients. In another meta-analysis of clinical observational studies (n = 145,608 unique patients on long term dialysis; n = 14 observational studies), anti-HCV sero-positive status was an independent and significant risk factor for death in patients on maintenance dialysis. The summary estimate for adjusted relative risk (all-cause mortality) was 1.35 with a 95% confidence interval (CI) of 1.25; 1.47 (P < 0.01) in anti-HCV positive patients on maintenance dialysis. An updated and stratified analysis (n = 4 studies, n = 91,916 patients on maintenance dialysis) resulted in an adjusted HR for cardiovascular mortality among anti-HCV positive patients of 1.21 (95% CI, 1.06; 1.39) (P < 0.01); the homogeneity assumption was not rejected. The mechanisms underlying such relationships remain unclear; it has been suggested that HCV promotes atherogenesis through direct and indirect mechanisms.

Clinical trials are under way to assess whether the clearance of HCV RNA from serum by direct-acting antiviral drugs reduces all cause or disease-specific (cardiovascular) mortality among patients on maintenance dialysis.