Direct acting antiviral agents (DAA) have revolutionized the management of Hepatitis C virus (HCV) positive kidney transplant recipients (KTR). The optimal timing of DAA therapy in KTR is not well defined. We analyzed the virologic response, graft function, proteinuria, donor specific antibodies (DAA), and acute rejection in 24HCV+ve KTRs who have completed DAA therapy (Rx) at our center. All patients received deceased donor kidney transplant, mean age at transplant was 56.5 yrs, 70% males, 70% blacks, 87.5% had genotype 1a. The median time from KT to initiation of DAA was 10.5 months (range 4-147). Ledipasvir/Sofosbuvir (83%) was the main DAA regimen. DAA Rxs were well tolerated except for anemia in 2 patients on Ribavarin. Of the 20 for whom the 12 wks post DAA follow up was available, 19 (95%) had achieved sustained virologic response. Of the remaining 4 patients, the viral loads were undetectable at the last follow-up. Certain DAA are known to interact with CNIs and there was a significant increase in CNI levels early into DAA therapy.

The outcomes were analyzed by separating the KTRs in 3 groups according to the time interval between KT and initiation of DAA- <6mnth (n=5), 6mnth-1yr (n=9), and >1yr (n=10). Serum creatinine and spot urine protein /creatinine ratio at 0, 3, 6, 9 and 12 months after initiating DAA therapy were analyzed using Wilcoxon signed ranks test. The creatinine levels and proteinuria from DAA initiation to last follow up was similar amongst the groups. Three patients (12.5%) developed de-novo DSA (2 in <6mnths and 1 in 6mnth-1yr group) with subclinical rejection on biopsy and received steroids (3), ivIg (3), and thymoglobulin (2). The treatment of rejection was administered concomitantly (2) or immediately after (1) the DAA therapy. All three patients achieved sustained virological response.

In conclusion, DAA were effective in treating HCV+ve KTRs. A minority of patients developed subclinical rejection with de-novo DSA after the initiation of DAA. Frequent CNI monitoring and dose adjustments are warranted during and post DAA therapy. Surveillance with DSA and allograft biopsies should be considered during and immediately after DAA therapy, especially within 1 yr post KT.

CITATION INFORMATION: Rege T, Hatahet K, Gillespie A, Ghanta M, Lee I, Qureshi K, Lau K, Karhadkar S, DiCarlo A, Constantinescu S, Rao S. Subclinical Rejections in Kidney Transplant Recipients Treated with Direct Acting Antiviral Agents for Hepatitis C Treatment within 1 Year of Transplant. Am J Transplant. 2017;17 (suppl 3).

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