Hepatitis C viral load, genotype, and increased risk of developing end-stage renal disease: REVEAL-HCV study

The association between hepatitis C virus (HCV) infection and end-stage renal disease (ESRD) remains controversial without considering the role of HCV viral load and genotype. This study aimed to determine whether HCV RNA level and genotype affect the risk of developing ESRD. Between 1991 and 1992, 19,984 participants aged 30-65 years were enrolled in a community-based prospective cohort study in Taiwan. Chronic HCV infection was defined by detectable HCV viral load. ESRD was determined as the need for chronic dialysis or renal transplantation. Conventional Cox proportional hazard and competing risk models were used to determine the hazard ratio (HR) for ESRD. After a median follow-up of 16.8 years, 204 cases were detected during 319,474 person-years. The incidence rates of ESRD for nonchronically HCV-infected and chronically HCV-infected patients were 60.2 and 194.3 per 100,000 person-years, respectively. The multivariable HR was 2.33 (95% confidence interval [CI] 1.40-3.89) when comparing patients with and without chronic HCV infection. Patients with low and high HCV RNA levels were at higher risk of ESRD than those who were nonchronically HCV-infected (HR, 2.11, 95% CI 1.16-3.86, and HR, 3.06, 95% CI 1.23-7.58; P_trend < 0.001). This association remained robust after taking pre-ESRD death as a competing event for ESRD. Patients with HCV genotype 1 tended to have a higher risk of developing ESRD (HR, 3.60 95% CI 1.83-7.07) compared with nonchronically HCV-infected subjects.

This study reveals that chronic HCV infection is associated with an increased risk of developing ESRD and suggests that elevated serum levels of HCV RNA (>167,000 IU/mL) and HCV genotype 1 are strong predictors of ESRD, indicating clinical implications for the management of chronic HCV. (Hepatology 2017;66:784-793).