Kidney transplant recipients (KTRs) with Hepatitis C virus infection (HCV+ve) have higher proteinuria and inferior patient and graft survival compared to HCV negative KTRs. Due to high incidence of rejection, interferon (IFN) based regimens are contraindicated in HCV+ve KTRs. Novel direct acting antivirals (DAA) are increasingly utilized for treatment of HCV in general population, with limited data in KTRs.

We studied virologic response, graft function, proteinuria, and acute rejection in 11 HCV+ve KTRs who completed DAA therapy (Rx); 7M:4F, mean age-59+/- 5yrs, AA (73%), diabetes mellitus (73%), hypertension (91%), all had deceased donor KT and were on CNIs, 6 donors were HCV+ve. All patients had detectable HCV viral load (genotype 1A-n=10, genotype 2-n=1) and majority had failed pre-transplant IFN Rx. The median time from KT to initiation of DAA was 13 months (range 6-124 months). DAA regimens utilized were Ledipasvir /Sofosbuvir (73%), Sofosbuvir /Simeprevir (18%) and Ribavirin/Sofosbuvir (9%). DAA Rxs were well tolerated with the exception of dose modification of ribavirin due to anemia.

Majority, 91% (10/11) had sustained virologic response at 12 weeks (SVR12) after completion of DAA Rx. There were no episodes of acute rejection associated with DAA Rx. Serum creatinine (SCr) and spot urine protein/creatinine ratio (Up/c) at 3 and 6 months pre- and post- DAA Rx were analyzed in the 10 patients who achieved SVR12. The mean SCr pre and post DAA Rx was similar (1.4mg/dl). There was a significant reduction in proteinuria, with median U p/c ratio pre-DAA Rx of 0.38mg/g (range 0.05-1.32mg/g) and median U p/c ratio post-DAA Rx of 0.18 mg/g (range 0.05-0.48 mg/g) (p=0.02).

In conclusion, DAA Rxs were highly effective, safe, and well tolerated in HCV+ve KTRs. The graft function remained stable during DAA Rx without any episodes of acute rejection. The decrease in proteinuria associated with SVR could represent the amelioration of HCV-related kidney effects and potentially improve graft survival. Further studies on the impact of successful treatment of HCV+ve KTRs with DAA on post-transplant diabetes, cardiovascular disease, and long term patient survival are warranted.

CITATION INFORMATION: Hatahet K, Ghanta M, Gillespie A, Lee I, El-Halawany H, Qureshi K, Lau K, Karhadkar S, Di Carlo A, Constantinescu S, Rao S. Treatment of Hepatitis C Viral Infection with Novel Direct Acting Antivirals in Kidney Transplant Recipients – Single Center Experience. Am J Transplant. 2016;16 (suppl 3).

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