Background:The optimal timing and duration of DAA therapy in HCV patients undergoing liver transplant(LT) is unknown. CRUSH-C is an open-label, Phase 2 study evaluating the safety and efficacy of short, perioperative ledipasvir(LDV)/sofosbuvir(SOF) for 4 weeks in HCV genotype(GT) 1 or 4 patients to prevent HCV recurrence post-LT.

Methods:25 patients, with chronic HCV GT 1 or 4, listed for LT, not receiving antiviral therapy, were enrolled to receive a single dose of LDV/SOF the day before LT followed by LDV/SOF for an additional 28 days post-LT. Patients were required to have a baseline eGFR ≥40 mL/min at screening and day of LT. Receipt of a liver from an anti-HCV positive donor was an exclusion criterion. Immunosuppression management was at investigator discretion.

Results:Interim data on the first 11 transplanted patients are available. Most patients were female(55%), Caucasian(82%), IL28B non-CC(64%). Four (36%) were treatment-experienced, all were GT 1. Baseline CTP class: A(27%), B(36%), and C(36%). The median MELD score was 13(range 7-16). 4/11 patients received a liver from a living donor. One patient met CrCl stopping rules (eGFR <30 mL/min) at Day 7, and discontinued. All other patients completed the planned therapy, 9/10(90%) have achieved SVR4; the patient with relapse has initiated protocol-defined retreatment with LDV/SOF for 12 weeks.

Treatment was safe and well tolerated. 9/11(82%) patients had an AE, the majority being mild or moderate. One grade 2 AE (dry eyes) was considered related to study drug. Three patients had SAEs: bile duct stenosis; acute kidney injury, elevated creatinine, and post-operative peri-incisional wound cellulitis; and decreased hepatic artery flow. All were assessed by the investigator as unrelated to study medication. No subjects have died or experienced graft loss. Updated results will be presented.

Conclusions:These preliminary data support the safe use of LDV/SOF in the immediate pre- and perioperative transplant period. Preemptive use of LDV/SOF administered as a single dose pre-LT and for 4 weeks following transplant may represent an effective strategy to prevent HCV recurrence.

CITATION INFORMATION: Verna E, Levitsky J, O'Leary J, Bzowej N, Moonka D, Hyland R, Brainard D, McHutchison J, Terrault N. Short Duration Perioperative Administration of Ledipasvir/Sofosbuvir Is Safe and Effective in Preventing HCV Recurrence After Liver Transplant. Am J Transplant. 2016;16 (suppl 3).

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