“
“Background. HCV recurrence after LT is associated with decreased patient and graft survival, and responds poorly to PEG-interferon/ribavirin (P/R) therapy (30% SVR). The addition

of an NS3/4A PI to P/R significantly increases SVR in non-LT patients, but SVR12 rates in LT recipients are unknown. Moreover, the safety and tolerability of TT remain major concerns. Aim. To evaluate safety and efficacy (SVR12) in LT recipients treated with TT. Methods. A total of 122 LT recipients with HCV from 6 US centers (57% GT1a, mean age 58y, 75% male, 45% advanced fibrosis [F3/4], 51% previously treated after LT [48% prior null responders]) were treated at a mean of 3.6y post-LT. Cyclosporine, tacrolimus, or other SAHA HDAC datasheet immunosuppressants were used in 59%, 30%, and 11%, respectively; 76% were also on mycophenolate. A P/R lead-in was used in 97% before the addition of telaprevir (89%) or boceprevir (11%). Efficacy analyses were limited to the 50 patients in whom P/R lead-in was <90d and were eligible to complete ≥51 weeks of TT and follow-up. Safety data were collected on all patients. Results. 36 patients

(72%) had end-of-treatment response (EOTR), and 28 (62%; 95% CI 47-76) SVR12. Of 31 (63%) patients achieving eRVR, 94% achieved EOTR and 89% SVR 12, but in those without eRVR, EOTR and SVR 12 were only 39% and 28%, respectively (P<0.001). In patients who received ≤36 wks of TT, SVR12 was achieved in 0/8 without eRVR but 3/4 with eRVR (P=0.02). In patients who received >36 wks of TT, SVR12 was achieved in 5/10 without eRVR Selleckchem GSK458 but 20/22 with eRVR (P=0.02). 90% of patients with EOTR achieved SVR12, yielding a relapse rate of 9.7%, all within 4 wks post-TT. Adverse events (AEs) led to interruption of TT in 30% and complete discontinuation in 20%. Treated rejection occurred MCE in 3.3% at a median of 168d of TT, but resulted in no graft losses. Maximum serum creatinine increased a median 0.4 (range 0.1-2.5) mg/dl on TT. Despite P/R dose reductions in 41%/82%

of patients, erythropoietin was used in 82%, and 52% required a median of 4 units of blood in the first 16 weeks of TT. 7 (5.7%) patients died, 5 of liver-related complications (4 had F3/4 and a mean MELD of 14 at the start of TT), at a median of 234d (range 22-336d) after starting the PI. Conclusions. In LT recipients with recurrent HCV, PI-TT increases SVR12 rates ∼2-fold compared to historical rates with P/R. Relapse after EOTR is uncommon, and occurs early. Duration of TT <36 weeks adversely affects SVR12, especially in those without eRVR, supporting treatment for a full 48 wks. Finally, the incidence and severity of AEs, particularly anemia and renal dysfunction, are considerably higher than in the non-LT population. Disclosures: R.