Estimating the causal effect of treatment with direct-acting antivirals on kidney function among individuals with hepatitis C virus infection

BACKGROUND: Direct-acting antivirals (DAA) are highly effective at treating Hepatitis C virus (HCV) infection, with a cure rate >95%. However, the effect of DAAs on kidney function remains debated. METHODS: We analyzed electronic health record data for DAA-naive patients with chronic HCV infection engaged in HCV care at Boston Medical Center between 2014 and 2018. We compared the following hypothetical interventions using causal inference methods: 1) initiation of DAA and 2) no DAA initiation. For patients with normal kidney function at baseline (eGFR>90 ml/min/1.73m(2)), we estimated and compared the risk for reaching Stage 3 chronic kidney disease (CKD) (eGFR≤60 ml/min/1.73m(2)) under each intervention. For patients with baseline CKD Stages 2–4 (15<eGFR≤90 ml/min/1.73m(2)), we estimated and compared the mean change in eGFR at 2 years after baseline under each intervention. We used the parametric g-formula to adjust our estimates for baseline and time-varying confounders. RESULTS: First, among 1390 patients with normal kidney function at baseline the estimated 2-year risk difference (95% CI) of reaching Stage 3 CKD for DAA initiation versus no DAA was -1% (-3, 2). Second, among 733 patients with CKD Stage 2–4 at baseline the estimated 2-year mean difference in change in eGFR for DAA initiation versus no DAA therapy was -3 ml/min/1.73m(2) (-8, 2). CONCLUSIONS: We found no effect of DAA initiation on kidney function, independent of baseline renal status. This suggests that DAAs may not be nephrotoxic; furthermore, in the short-term, HCV clearance may not improve CKD.