Direct Acting Antivirals in Hepatitis C-Infected Kidney Transplant Recipients: Associations with Long-term Graft Failure and Patient Mortality

Abstract

Background: Direct-acting antiviral (DAA) therapy among hepatitis C virus (HCV)-infected kidney transplant recipients is associated with short-term improvement in protein/creatinine (P/C) ratios, but how HCV cure affects long-term graft outcomes remains unknown. Methods: This is a retrospective follow-up study of 59 HCV-infected patients who underwent kidney transplant at the University of Alabama at Birmingham between 2007-2015 who were followed until the end of 2017. We examined the association of DAA-induced HCV cure with graft failure or death by survival analyses (Kaplan-Meier, Cox regression). Redsults: Mean age was 55 years, 73% were African American, and 68% were male. Median baseline creatinine was 1.4 mg/dL, P/C ratio was 0.5, and estimated glomerular filtration rate (eGFR) was 59 mL/min. Of those who received DAA, 24 (83%) achieved cure. The remaining 5 DAA patients (17%) did not have documented evidence of sustained virologic response (SVR). Overall, 19 (32%) patients experienced graft failure or death; with lower incidence in treated patients than untreated (4 vs 15 events; 2.6 vs 10.3 per 100 person-years [cHR 0.19, 95% CI: 0.06–0.66]). When adjusted for age, sex, race, and proteinuria, the association remained strong and invariant across time-varying (aHR 0.30, 95% CI: 0.08–1.10), time-averaged (aHR 0.28, 95% CI: 0.07–1.07), and time-varying-cumulative (aHR 0.32, 95% CI: 0.08–1.21) proteinuria metrics. Conclusions: DAAs therapy was associated with improved graft survival and reduced mortality. While not statistically significant, the association was strong, and these single-center findings warrant larger studies to demonstrate the benefits of HCV treatment in this population.

Keywords

• direct-acting antivirals
• kidney transplant
• hepatitis c virus
• proteinuria
• mortality
• graft failure
• outcomes